Biochem

You are seeing a 28 year old female with PKU. She and her partner would like to start a family within the next year or so. He does not have PKU, yet we do not know if he is a carrier or not. What is the likely risk to have an affected baby? 1/120 1/80 1/100 1/60 1/40 1/140 1/150

1/100

An Amish couple are first cousins. They inquiry about the chance to have a child with VLCADD as they have an common maternal uncle with this disease (i.e. her mother's brother and his mother's brother is affected, and their mothers are sisters). VLCADD is inherited in an autosomal recessive manner. That chance that a future child of theirs would have VLCADD is? 1/8 1/16 1/36 1/64

1/36

For the majority of patients who have a child with an inborn error of metabolism, what is the most likely risk for having another affected child (same disease) during a future pregnancy? Negligible 25% 50% 5-6%

25%

The first born child of a couple has a mitochondrial disease that was diagnosed early in life. Without knowing what disease, what is the most likely recurrence risk for having another affected child? 25% since most mitochondrial diseases are caused by nuclear DNA mutations. 50% since most mitochondrial diseases are caused by nuclear DNA mutations. 100% since most mitochondrial diseases are inherited through maternal inheritance of mutated mitochondrial DNA but with variability in presentation. Virtually 0% since most mitochondrial diseases are caused by sporadic mutations within mitochondrial DNA.

25% since most mitochondrial diseases are caused by nuclear DNA mutations.

Select the group of disorders that most commonly presents with episodic vomiting, lethargy and hypoketotic hypoglycemia that can progress to coma and even death. Fatty acid oxidation disorders Mitochondrial Urea Cycle Disorders Glycogen Storage Diseases Lysosomal

Fatty acid oxidation disorders

A newborn screen shows elevated propinylcarnitine (C3) on acylcarnitines. The differential diagnosis includes all of the following except: Methylmalonic acidemia caused by methylmalonyl-CoA mutase deficiency Methylmalonic acidemia caused by cobalamin disorders Propionic acidemia caused by deficiency of propionyl CoA carboxylase Glutraric Acidemia Type I due to Glutaryl-CoA dehydrogenase deficiency Maternal Vitamin B12 (cobalamin) deficiency

Glutraric Acidemia Type I due to Glutaryl-CoA dehydrogenase deficiency

Match the clinical presentation with the most important aspect of treatment for that disorder. Answers are only used once. 80 year old with intellectual disability, seizures, and ezcema Modified diet (low protein/medical formula) Modified diet (low protein/medical formula) and scavenger medication Modified diet (low protein/medical formula) and supplementation amino acids Illness precautions and hospitalizations for all fevers

Modified diet (low protein/medical formula)

Consider the scenario in the previous question which a newborn screen shows elevated propinylcarnitine (C3 acylcarnitine). If you could only select one test, which one would be the best test to narrow the differential diagnosis? Plasma amino acids Plasma acylcarnitine Plasma carnitine Urine organic acids Urine acylglycine Plasma organic acids

Urine organic acids

Consider the scenario in the previous question where a neonate has a positive newborn screen for an elevated tyrosine. Which is the most important metabolic evaluation for this neonate? Plasma amino acids to look at phenyalanine Urine organic acids for homgentisic acid Urine organic acids for succinylacetone CSF for glycine levels

Urine organic acids for succinylacetone

When thinking globally about metabolism, fatty acid oxidation is so important in the body because it produces ketones as well as supplies energy to drive gluconeogenesis metabolize toxic organic acids drive the urea cycle release insulin into the blood stream

drive gluconeogenesis

For a normal person, if the supply of glucose is diminished (e.g. from fasting), the level of ketones in the body should _____. increase decrease

increase

Complete the sentence: Kuvan (Sapropterin dihydrochloride - BH4) is a cofactor for the PAH enzyme. works in everyone that has PKU. is an inexpensive way to treat PKU. allows people with PKU to eat a regular diet.

is a cofactor for the PAH enzyme.

Because of significant phenotypic overlap, urine glycosaminoglycan (GAG) analysis is a useful screening test when evaluating for ______disorders. peroxisomal lysosomal mitochondrial carbohydrate metabolism

lysosomal

"Carnitine is plays a critical role in energy production. It transports long-chain fatty acids into the mitochondria so they can be oxidized ("burned") to produce energy." Another main function of carnitine includes: binding to toxic metabolites to be removed from body providing the carbon backbone for gluconeogenesis acting as a cofactor for biotin metabolism maintaining the pH balance of blood

binding to toxic metabolites to be removed from body

Match mitochondria disorder to molecular DNA findings. MELAS mtDNA point mutation A3243G Heterozygous for two pathogenic mutations in the POLG gene found on Nuclear DNA (AR inheritance) Large (5kb) mtDNA deletion

mtDNA point mutation A3243G

You are consulted on a 7 day old old baby girl. She is hypotonic, dysmorphic, has seizures, and hepatic disease. Bloodwork shows extremely low plasmalogens and elevated phytanic acid and pipecolic acid, and elevated very long chain fatty acids. Which is FALSE about this disorder? stippling of epiphyses is present on x-ray prognosis is poor it is an autosomal recessive disorder EM will demonstrate absence of the peroxisome none are false (all are true)

none are false (all are true)

A woman with PKU has had great metabolic control of her Phe levels and becomes pregnant. She continues to maintain control of her Phe levels. Her baby is at risk to have PKU, too at risk for microcephaly not at greater risk for negative outcomes at risk for congenital heart defects

not at greater risk for negative outcomes

Plasmalogens are an important membrane component in tissue such as the heart or brain. A person with a _______ disorder will have low plasmologens on metabolic testing. peroxisomal lysosomal mitochondrial carbohydrate metabolism

peroxisomal

Which ONE of the following tests is NOT typically helpful or a part of the diagnostic work-up of a child suspected of having a Lysosomal Disease such as MPS III (Sanfilippo)? urine MPS screen eye examination skeletal x-rays enzyme assay for the suspected disease plasma amino acids

plasma amino acids

A first tier test to screen to check for Zellweger syndrome is: karyotype plasma amino acids plasma very long chain fatty acid levels (VLCFA) skeletal x-rays

plasma very long chain fatty acid levels (VLCFA)

A 38 year old woman complains of recurrent hand pain and abdominal bloating. An EKG shows left ventricular hypertrophy. Her brother and maternal uncle both have had renal transplants and have hearing loss and chronic pain. Which of the following answers is FALSE? this is an X-linked condition she is not at risk of developing renal complications treatment with enzyme replacement therapy MAY be beneficial to her physical exam would likely show angiokertomas of the skin

she is not at risk of developing renal complications

Threshold the mutant load of varies from cell to cell the primordial germ cell divides and the resulting mature ovum has a larger portion of mutant mitochondria some tissues need more energy than others, so they are more likely to present with disease

some tissues need more energy than others, so they are more likely to present with disease

Heteroplasmy the mutant load of varies from cell to cell the primordial germ cell divides and the resulting mature ovum has a larger portion of mutant mitochondria some tissues need more energy than others, so they are more likely to present with disease

the mutant load of varies from cell to cell

Bottleneck the mutant load of varies from cell to cell the primordial germ cell divides and the resulting mature ovum has a larger portion of mutant mitochondria some tissues need more energy than others, so they are more likely to present with disease

the primordial germ cell divides and the resulting mature ovum has a larger portion of mutant mitochondria

In which disorder would you find complete absence of the peroxisomes? x-linked adrenoleukodystrophy rhizomelic chondrodysplasia punctata neonatal ALD zellweger syndrome

zellweger syndrome

A person with galactosemia has a severe mutation (resulting in no protein product) and a Duarte variant. We would expect the approximate GALT enzyme activity to be: ~75% ~50% ~25% ~0%

~25%

Mitochondrial disease is a multisystem disease. Of the following symptoms, which would be least likely to be a clue for a mitochondrial disease? cafe au lait macules arrythmia retinopathy migranes pancreatic dysfunction short stature Seizures

cafe au lait macules

Which of the following is TRUE about Tay-Sachs? 1/500 carrier frequency in Ashkenazi Jewish population cafe noir spots in macula carrier screening is recommended before pregnancy carrier screening measures HexC enzyme activity in blood

carrier screening is recommended before pregnancy

A 55 year old male patient presents to the clinic with jaundice, tremors, migraines, depression and noticeable Kayser-Fleischer rings. What substance is likely building up in his body? Copper Tyrosine Argine Leucine Iron

Copper

All of the following are typical features of Hunter syndrome (MPS II) EXCEPT: Dysostosis multiplex Corneal Clouding on Eye Exam Coarse facies Hepatomegaly

Corneal Clouding on Eye Exam

Which basic lab will tell you if a person is acidotic and has an elevated anion gap? Electrolytes & blood gas CBC Lactate Glucose LFT (Liver Function Test )

Electrolytes & blood gas

Select the best metabolic lab test to investigate the following metabolic disease. A lab test may be chosen more than once. OTC Ammonia CBC Glucose Orotic Acid Plasma Amino Acids Plasma Organic Acids Urine Amino Acids Urine Organic Acids

Orotic Acid

There are many different types of metabolic diets. when thinking broadly, given the two examples below, match it with the correct disorder Moderate to high total protein (primarily from metabolic formula), restrictions in certain amino acids (protein restriction from food). OTC PKU

PKU

Given the category of metabolic disease, match the "best" or the primary biochemical laboratory to help establish the diagnosis. Organic Acid Disorders Plasma Acylcarnitine Plasma Amino Acids Plasma Organic Acids Urine Acylcarnitine Urine Amino Acids Urine Organic Acids

Urine Organic Acids

Select the best metabolic lab test to investigate the following metabolic disease. A lab test may be chosen more than once. Proprionic Acidemia Ammonia CBC Glucose Orotic Acid Plasma Amino Acids Plasma Organic Acids Urine Amino Acids Urine Organic Acids

Urine Organic Acids

An infant presents with vomiting, lethargy, and tachypnea. You are concerned about an organic acidemia. What routine, basic, blood test will yield the best information regarding metabolic acidosis? Liver function tests Blood glucose Electrolytes with anion gap Blood ammonia Heme survey

Electrolytes with anion gap

A 34 year old pregnat woman comes to see you because her father has MELAS. The risk that th efetus is affected with MELAS is closest to 0% 25% 50% 100%

0%

A 10 year old male has a history of progressive external ophthalmoplegia, vision loss, proximal muscle weakness and lactic acidosis. DNA testing was done to confirm his diagnosis. What do you expect the reult to show? A point mutation in mitochondrial DNA A point mutation in nuclear DNA A large deletion in mitochondrial DNA A large deletion in nuclear DNA

A large deletion in mitochondrial DNA

When evaluating a neonate for an inborn error of metabolism, what initial basic lab(s) is/are helpful: Blood glucose Ammonia Lactate Electrolyes with anion gap Liver function tests Urine ketones All of these tests

All of these tests

Each Biochemical test has advantages and disadvantages. Match the disadvantage with the listed biochemical test Amino acid analysis Multiple analytes can have the same mass to charge ratio Analysis takes a long time, may need to repeat in times of acute illness Analysis takes a long time, may identify unusual species

Analysis takes a long time, may identify unusual species

Each Biochemical test has advantages and disadvantages. Match the disadvantage with the listed biochemical test Organic acid analysis analysis Multiple analytes can have the same mass to charge ratio Analysis takes a long time, may need to repeat in times of acute illness Analysis takes a long time, may identify unusual species

Analysis takes a long time, may need to repeat in times of acute illness

Treatment of some urea cycle disorders, such as citrullinemia type 1, includes supplementation of the amino acid ___ to increase the rate of urea production. Glycine Arginine Isoleucine Leucine

Arginine

In urea cycle disorders, the amino acids _____ and/or _____ are used as treatment supplements to stop the urea cycle. Glutamate Proline Tyrosine Glutamine Arginine Leucine Valine Citrulline

Arginine Citrulline

What is the most common form of inheritance for mitochondrial diseases? Autosomal Recessive Sporadic Maternal X-Linked Autosomal Dominant

Autosomal Recessive

Which is the single most important component of the treatment protocol for children with fatty acid oxidation disorders? Low fat diet Carnitine supplementation Avoid fasting MCT oil with exercise

Avoid fasting

The peroxisome is involved with many biochemical processes. One of the main roles the peroxisome helps produce metabolic energy is through: Amino acid biosynthesis Beta oxidation of VLCFAs Polysaccharide biosynthesis Protein degradation

Beta oxidation of VLCFAs

All babies with hyperphe should be screened for Pyridoxine (B6) defects Branched chain amino acid defects Carnitine defects Cobalamin defects Biopterin defect

Biopterin defect

An Amish child is found to have seizures and hearing loss at 8 months of age. His skin is dry and he has areas of redness around his mouth and eyes (i.e. eczema). Urine organic acids show 3 hydroxy-isovaleric acid and lactate; plasma acylcarnitines show elevated C3 and C5OH. What is the most important intervention? Valproic acid for seizure control Enzyme testing for MMA. Biotin supplementation Carnitine supplementation Medical formula and protein restriction

Biotin supplementation

A neurologist refers a 4 year old female with seizures, mild developmental delays, alopecia and a persistent rash for evaluation. What is the most likely diagnosis? Tyronsinemia Biotinidase deficiency Methylmalonic acidemia due to B12 deficiency Homocystinuria Classical PKU

Biotinidase deficiency

Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). What are possible therapies ADA? Select all that apply. Liver transplant Bone marrow transplant Enzyme replacement therapy IV Antibiotics Restricted protein in diet Gene Therapy

Bone marrow transplant Enzyme replacement therapy Gene Therapy

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. Propionic Acidema is a type of organic acidemia. Left untreated and in the severe state, it presents with overwhelming illness. This is because of Substrate accumulation Byproduct accumulation Product deficiency

Byproduct accumulation

In a simplistic view, all fats, proteins, and sugars are converted to ________, which then goes into the Kreb's cycle, which then ultimately becomes ATP a. Lactose b. NADH c. Acetyl-CoA d. ammonia e. Ketones

C

Which of the following is NOT a criteria for inclusion on the Wisconsin Newborn Screening Panel Information is available on the incidence, morbidity and mortality, and the Can cause serious health risks in adulthood that are unlikely to be detected Linked with safe and effective interventions that have been test in well- The tests characteristics should be known, including specificity, sensitivity,

Can cause serious health risks in adulthood that are unlikely to be detected

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are due to different defects within the same metabolic pathway. As such, there can be significant overlap in the clinical presentation, with the exception on one defining feature. Match that feature to the disease. PA Cardiomyopathy Renal disease

Cardiomyopathy

A newborn rapidly develops apnea and intractable seizures after birth. Prenatally his mother noticed the fetus having frequent hiccups. The baby's ammonia and newborn screen are normal. What is the most important diagnostic test in this infant? Plasma biotinidase enzyme activity Urine organic acids for orotic acid Plasma acylcarnitines for odd chain fats Cerebral spinal fluid for amino acids for glycine

Cerebral spinal fluid for amino acids for glycine

Match the biochemical findings with the clinical presentation. Clinical presentations listed may be classical or non-classical. (Use each answer once) Urine organic acids - 3OH glutaric acid Child with with onset of dystonia after fever and illness Teenage with intellectual disability and renal insufficiency School age Amish child with cardiomyopathy

Child with with onset of dystonia after fever and illness

The Newborn Screen detects the following disorders (check all that apply): Citrullinemia type 1 Ornithine transcarbamylase deficiency (OTC) ArgininoSuccinate Lyase Deficiency (ASL) Deficiency Carbomyl Phosphate Synthetase deficiency ArgininoSuccinate Synthetase (ASS) Deficiency

Citrullinemia type 1 ArgininoSuccinate Lyase Deficiency (ASL) Deficiency ArgininoSuccinate Synthetase (ASS) Deficiency

Orotic acid is elevated in the following disorders (check all that apply): Citrullinemia type 1 NAGS deficiency Ornithine transcarbamylase deficiency Carbomyl Phospate Synthetase deficiency

Citrullinemia type 1 Ornithine transcarbamylase deficiency

A 17 year old male is 6' 5" (his father is 6' and mother is 5' 4"), has learning disabilities, downward dislocated lenses and was once hospitalized for a stroke like episode. What is the most likely diagnosis? Classical homocystinuria Marfan syndrome Propionic acidemia Galactosemia Tyrosinemia Type 1

Classical homocystinuria

When women with PKU do not have their phenylalanine levels in the therapeutic range (e.g. 2-6 mg/dL) during pregnancy, their babies are at significant risk to develop maternal PKU syndrome. This syndrome includes all of the following symptoms except: Intrauterine growth retardation Intellectual disability Decreased pigmentation Congenital heart disease Microcephaly

Decreased pigmentation

Several metabolic disease present with similar clinical picture. Match the disorder with its possible clinical presentation if not treated. Homocystinuria Developmental Delay with no acute decompensation Recurrent episodes of vomiting and lethargy with mild illness

Developmental Delay with no acute decompensation

Several metabolic disease present with similar clinical picture. Match the disorder with its possible clinical presentation if not treated. PKU Developmental Delay with no acute decompensation Recurrent episodes of vomiting and lethargy with mild illness

Developmental Delay with no acute decompensation

A mutation within the POLG gene is an example of what type of mitochondrial disease? Disease caused by mitochondrial DNA deletion Disease caused by mitochondrial DNA depletion Disease caused by mitochondrial DNA point mutation

Disease caused by mitochondrial DNA depletion

Match the disorder of carbohydrate metabolism to clinical and laboratory findings GSD V (McArdles) Normal glucose and lactic acid levels, liver disease (abnormal AST/ALT, high bilirubin) Elevated CK (creatine kinase), recurrent rhabdomyolysis Hepatomegaly, recurrent ketotic hypoglycemia, neutropenia, lactic acidosis, hyperlipidemia

Elevated CK (creatine kinase), recurrent rhabdomyolysis

Which basic lab will tell you if a person is acidotic and has an elevated anion gap? Electrolytes CBC BUN (blood urea nitrogen) Lactate Glucose LFT (Liver Function Test )

Electrolytes

A 15 year old female presents with intermittent abdominal pain, cyclic vomiting, significant bowel irregularity, extreme anxiety with reports of hallucinations, which seem to be worse during her menstrual cycle. Which test result would be considered diagnostic for the condition you are considering? Reduced PBG (porphyrin precursor porphobilinogen) in urine Elevated creatinine in the urine Elevated PBG (porphyrin precursor porphobilinogen) in stool Elevated creatinine in the blood Elevated PBG (porphyrin precursor porphobilinogen) in saliva sample

Elevated PBG (porphyrin precursor porphobilinogen) in stool

Ragged Red Fibers found on microscopy are only found in MELAS disease. T/F

F

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once nerve pain in hands and feet, recurrent abdominal pain, reduced sweating, angiokeratomas, strokes, renal failure Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Fabry Disease

All of the following disease-organelle relationships are correct EXCEPT: Infantile Refsum disease-peroxisome GSD II (Pompe)-lysosome Fabry-peroxisome Hunter-lysosome

Fabry-peroxisome

When recalling the ACUTE clinical presentation of a metabolic disorders (such as with MSUD) vs. a chronic clinical presentation (such as with PKU), which of the following would NOT be a typical symptom? Coma Lethargy Seizures Vomiting Tachypnea Failure to Thrive (FTT) Death

Failure to Thrive (FTT)

Cherry Red Spots are diagnostic for Tay Sachs disease. True False

False

Everyone responds to Kuvan (Sapropterin dihydrochloride - BH4), to a varying degree. True False

False

Hyperphenylalanemia is only caused by phenylalanine hydroxylase deficiency. True False

False

In someone with a urea cycle disorder, there is always an elevated anion gap. True False

False

OTC is screened for on NBS True False

False

Only males can be severely affected by OTC deficiency. True False

False

People with McArdle's Disease (GSD Type V) should avoid all exercise. True False

False

Which of the following statements regarding X-linked adrenoleukodystropy (X-ALD) is FALSE? Current treatment methods include both allogeneic and/or autologous hematopoietic stem cells transplant therapies has been shown to decrease demyelination progression. Neurological deterioration and other symptoms are due to the accumulation of saturated very-long-chain fatty acids (VLCFA). Females are carriers and as such do not have any signs or symptoms of this disease All males affected with X-ALD will develop ALD associated symptoms within their lifetime.

Females are carriers and as such do not have any signs or symptoms of this disease

In general, the diet and treatment for metabolic diseases includes: A. Providing just enough of the offending nutrient for normal function, growth and development. Limit excess intake that isn't needed B. Ensure adequacy of every other macro- and micro-nutrient C. Supplement what the individual cannot produce themselves(conditionally essential nutrients). D. Provide additional coenzyme/co-factors to try to improve enzyme activity E. Provide substances that help rid the body of the accumulating F. Prevent fasting G. All of these

G

Guanidinoacetate methyltransferase (GAMT) is a type of creatine disorder. A 2-year-old male with developmental delays, seizures, and involuntary muscle contractions presents to clinic and the provider is concerned for GAMT. Which toxic metabolite is elevated in the brain when GAMT is not working? GAA (Guanidinoacetate) Glycine Creatine Creatine:Creatinine ratio Arginine Creatinine

GAA (Guanidinoacetate)

Match the biochemical finding with the enzyme defect in galactose metabolism. Options are used only once. Normal GALT activity and elevated galactose-1-phosphate (gal-1-P) and normal galactitol. GALE GALK GALT

GALE

Match the biochemical finding with the enzyme defect in galactose metabolism. Options are used only once. Normal GALT activity, low galactose-1-phosphate (gal-1-P), elevated galactitol and elevated total galactose GALE GALK GALT

GALK

Match the biochemical finding with the enzyme defect in galactose metabolism. Options are used only once. No GALT activity, Elevated galactose-1-phosphate (gal-1-P) and elevated galactitol, elevated galactose GALE GALK GALT

GALT

Match the glycogen storage disease with the classical clinical presentation. Options are used only once. Massive hepatomegaly in infancy, recurrent hypoglycemia, failure to thrive GSD Type 1a ( VonGierke) GSD Type II (Pompe) GSD Type V (McArdles)

GSD Type 1a ( VonGierke)

Match the glycogen storage disease with the classical clinical presentation. Options are used only once. Infantile cardiomyopathy, death if untreated GSD Type 1a ( VonGierke) GSD Type II (Pompe) GSD Type V (McArdles)

GSD Type II (Pompe)

Match the glycogen storage disease with the classical clinical presentation. Options are used only once. Recurrent episodes of rhabdomyolysis in adulthood, muscle cramps, fatigue, elevated CK GSD Type 1a ( VonGierke) GSD Type II (Pompe) GSD Type V (McArdles)

GSD Type V (McArdles)

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once Hepatosplenomegaly, bone pain, thrombocytopenia, anemia Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Gaucher Disease

Stroke or seizures occur in all of the following EXCEPT: Gaucher Disease Type 1 MELAS Fabry Zellweger syndrome

Gaucher Disease Type 1

A lysosomal storage disease that does NOT typically involve the central nervous system is: Hunter syndrome Gaucher disease Type I Tay-Sachs disease Fabry Disease Hurler syndrome

Gaucher disease Type I

There are 13 forms of Neuronal ceroid lipofuscinoses (NCL) (also called Batten disease). Which of the following is the most promising treatment for ALL of the different forms? Enzyme Replacement Therapy All of the these Cell Therapy: Stem Cell Transplant Gene Therapy Cell Therapy: Bone Marrow Transplant

Gene Therapy

You are called by newborn screening with a possible positive result for galactosemia in a 5 day old baby. Which of the following action is the most important first step to take? Repeat the newborn screen and allow the child to continue breast feeding until the disorder is confirmed or ruled out. Send quantitative GALT enzyme activity to confirm the diagnosis. Send DNA testing to see if the child has the Duarte variant. Eye exam to look for cataracts. Have the mother stop breast feeding and start feeding the infant a soy based formula.

Have the mother stop breast feeding and start feeding the infant a soy based formula.

Match the disorder of carbohydrate metabolism to clinical and laboratory findings GSD 1a (von Gierke) Normal glucose and lactic acid levels, liver disease (abnormal AST/ALT, high bilirubin) Elevated CK (creatine kinase), recurrent rhabdomyolysis Hepatomegaly, recurrent ketotic hypoglycemia, neutropenia, lactic acidosis, hyperlipidemia

Hepatomegaly, recurrent ketotic hypoglycemia, neutropenia, lactic acidosis, hyperlipidemia

MELAS can present in various ways. For example, a 1 year old boy has lactic acidosis and muscle weakness. His sister has had stroke like episodes. His mother and maternal grandmother have depression, migraines and muscle fatigue. His maternal uncle has cardiomyopathy and sensory hearing loss. Which one of the following answers is the best explanation for the spectrum of disease presentation? Heteroplasmy Bottleneck Threshold Maternal Inheritance

Heteroplasmy

Match mitochondria disorder to molecular DNA findings. Mitochondrial Depletion Disorder mtDNA point mutation A3243G Heterozygous for two pathogenic mutations in the POLG gene found on Nuclear DNA (AR inheritance) Large (5kb) mtDNA deletion

Heterozygous for two pathogenic mutations in the POLG gene found on Nuclear DNA (AR inheritance)

A neonate has a positive newborn screen for elevated tyrosine. Which of the following is the least likely cause for this finding? Liver failure Tyrosinemia Type 1 Transient tyrosinemia due to hepatic immaturity Homocystinuria

Homocystinuria

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once coarse facies, regression, pebbly skin, behavior problems, X-linked inheritance Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Hunter Disease (MPS II)

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once Coarse facies, hepatosplenomegaly, corneal clouding, short stature, bony deformities, developmental regression Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Hurler Disease (MPS1)

Respiratory chain disorders are related to mutations with the nuclear genes. Mutations within the genes results in serious signs and symptoms in affected individuals. Based on what you know about the biology and function of mitochondria, which one of the following is the least likely finding in these patients? cardiomyopathy Hypocalcemia Hypotonia Lactic acidosis Seizures

Hypocalcemia

When thinking about fatty acid oxidation disorders, we would expect someone to clinically present during illness with: Hypoglycemic / Hypoketotic Hypoglycemic / Hyperketotic Hyperglycemic / hypoketotic Hyperglycemic / hyperketotic

Hypoglycemic / Hypoketotic

A patient with an IEM is acutely ill and has to be admitted to the hospital. What is the most effective way to turn off fat and protein metabolism during the catabolic state and make the body go into an anabolic state? IV D10 Normal Saline IV Lipids IV ATP IV Amino Acids IV D10 Water

IV D10 Normal Saline

Match the clinical presentation with the most important aspect of treatment for that disorder. Answers are only used once. 2 year old with seizures and movement disorder. Brain MRI shows changes to the basal ganglia and subdural hemorrhages. Modified diet (low protein/medical formula) Modified diet (low protein/medical formula) and scavenger medication Modified diet (low protein/medical formula) and supplementation amino acids Illness precautions and hospitalizations for all fevers

Illness precautions and hospitalizations for all fevers

You are seeing a 13 year old girl with well controlled classical galactosemia. Which of the following counseling issues is important to discuss? Teratogenic effects of poorly controlled disease during pregnancy Autosomal dominant inheritance Ovarian failure and infertility Neurological deterioration with poor compliance in adulthood

Ovarian failure and infertility

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once nerve pain in hands and feet, recurrent abdominal pain, reduced sweating, angiokeratomas, strokes, renal failure CNS degeneration during infancy, irritability, seizures, hypertonia Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Krabbe Disease

Which disorder of fatty acid oxidation has a more severe presentation? MCADD SCADD VLCADD LCHADD

LCHADD

Match mitochondria disorder to molecular DNA findings. Kearn Sayres mtDNA point mutation A3243G Heterozygous for two pathogenic mutations in the POLG gene found on Nuclear DNA (AR inheritance) Large (5kb) mtDNA deletion

Large (5kb) mtDNA deletion

A toddler presents during illness with lethargy and ataxia. His urine is observed to smell sweet. He is found on plasma amino acids and urine organic acids to have a metabolic disorder. His treatment should include restriction of which amino acid: Leucine Alllo-isoleucine Isoleucine Valine Methionine

Leucine

Locus Heterogeneity is defined as "The same phenotype is caused by mutations in genes at different chromosomal loci." Which disorder is an example of locus heterogeneity? Tay Sachs Disease Niemann Pick A Disease MPS III (Sanfilippo Syndrome)

MPS III (Sanfilippo Syndrome)

Consider the scenario from the previous question in which a 2 year old is found comatose in her crib in the morning by her mother. (Her mother cannot revive her. Last night she had a mild vomiting illness and fed poorly during the day. She is brought to the ER and her blood sugar is 25 and the urinalysis shows no ketones.) Based on clinical presentation and incidence in the population, what is the most likely metabolic disorder? Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD) Maple Syrup Urine Disease (MSUD) Very long-chain acyl-CoA dehydrogenase (VLCADD)

Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD)

Menkes disease has variable expressivity, locus homogeneity and allelic heterogeneity. Which of the following answers displays all of these concepts correctly? Menkes disease presents only in children with neurodegeneration, mutations in ATP7A ABCD1, and GMAT can cause Menkes disease, There is one common mutation in the ATP7A gene that causes the neurodegeneration in children. Menkes disease presents only in children with neurodegeneration, only mutations in ATP7A cause Menkes, different mutations within the ATP7A gene can cause different phenotypic manifestations Menkes disease can range from mild to severe, only mutations in ATP7A cause Menkes disease, and different mutations within the ATP7A gene can cause different phenotypic manifestations Menkes disease can range from mild to severe, only mutations in ATP7A cause Menkes disease, there is one common mutation with ATP7A that causes the different phenotypic manifestations

Menkes disease can range from mild to severe, only mutations in ATP7A cause Menkes disease, and different mutations within the ATP7A gene can cause different phenotypic manifestations

All of the following are typical complications of UNTREATED classical galactosemia EXCEPT? Hepatic failure Cataracts Death E.coli sepsis (blood infection) Mild speech articulation delays

Mild speech articulation delays

With many metabolic diseases there is a wide range of clinical presentation possible due to genotype/phenotype correlation. For example, a mild or later onset presentation disease may be due to a _____ mutation. Null Missense

Missense

Match the clinical presentation with the most important aspect of treatment for that disorder. Answers are only used once. Toddler with failure to thrive and vomiting who avoids high protein food (e.g. milk). Normal newborn screen. Modified diet (low protein/medical formula) Modified diet (low protein/medical formula) and scavenger medication Modified diet (low protein/medical formula) and supplementation amino acids Illness precautions and hospitalizations for all fevers

Modified diet (low protein/medical formula) and scavenger medication

Match the clinical presentation with the most important aspect of treatment for that disorder. Answers are only used once. 8 year old Mennonite boy with normal growth and development but identified as affected after his sister died at 6 days of life with encephalopathic crisis. Modified diet (low protein/medical formula) Modified diet (low protein/medical formula) and scavenger medication Modified diet (low protein/medical formula) and supplementation amino acids Illness precautions and hospitalizations for all fevers

Modified diet (low protein/medical formula) and supplementation amino acids

Each Biochemical test has advantages and disadvantages. Match the disadvantage with the listed biochemical test Acylcarnitine analysis Multiple analytes can have the same mass to charge ratio Analysis takes a long time, may need to repeat in times of acute illness Analysis takes a long time, may identify unusual species

Multiple analytes can have the same mass to charge ratio

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once Massive Hepatosplenomegaly, developmental regression, failure to thrive Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Nieman Pick A

If you could only choose one of the followings labs, which one will diagnosis Fabry Disease in a clinically affected male? None of these labs Plasma Amino Acids Urine Organic Acids Plasma Acylcarnitines Newborn Screening

None of these labs

Select the condition that most commonly presents in the infantile/neonatal period with progressive lethargy, seizures which can occur in utero, hypotonia, myoclonic jerks leading to apnea and often death by 1 year (survivors have severe MR and intractable seizures). MSUD Nonketotic hyperglycinemia Proprionic acidemia Isovaleric Acidemia OTC deficiency

Nonketotic hyperglycinemia

Match the disorder of carbohydrate metabolism to clinical and laboratory findings Galactosemia Normal glucose and lactic acid levels, liver disease (abnormal AST/ALT, high bilirubin) Elevated CK (creatine kinase), recurrent rhabdomyolysis Hepatomegaly, recurrent ketotic hypoglycemia, neutropenia, lactic acidosis, hyperlipidemia

Normal glucose and lactic acid levels, liver disease (abnormal AST/ALT, high bilirubin)

There are many different types of metabolic diets. when thinking broadly, given the two examples below, match it with the correct disorder Moderately low total protein (very close to the DRI), supplemented with essential amino acids. OTC PKU

OTC

What is the likely diagnosis in a 3 day old infant who develops lethargy vomiting, respiratory alkalosis and hyperammonemia with undetectable citrulline on plasma amino acids? Arginase deficiency Propionic acidemia Ornithine transcarbamylase deficiency ArgininoSuccinate Synthetase (ASS) Deficiency Nonketotic hyperglycinemia Citrullinemia type 1 ArgininoSuccinate Lyase Deficiency (ASL) Deficiency

Ornithine transcarbamylase deficiency

Given the category of metabolic disease, match the "best" or the primary biochemical laboratory to help establish the diagnosis. Fatty Acid Oxidation Disorders Plasma Acylcarnitine Plasma Amino Acids Plasma Organic Acids Urine Acylcarnitine Urine Amino Acids Urine Organic Acids

Plasma Acylcarnitine

Given the category of metabolic disease, match the "best" or the primary biochemical laboratory to help establish the diagnosis. Amino Acid Disorders Plasma Acylcarnitine Plasma Amino Acids Plasma Organic Acids Urine Acylcarnitine Urine Amino Acids Urine Organic Acids

Plasma Amino Acids

Given the category of metabolic disease, match the "best" or the primary biochemical laboratory to help establish the diagnosis. Urea Cycle Disorders Plasma Acylcarnitine Plasma Amino Acids Plasma Organic Acids Urine Acylcarnitine Urine Amino Acids Urine Organic Acids

Plasma Amino Acids

Select the best metabolic lab test to investigate the following metabolic disease. A lab test may be chosen more than once. Citrullinemia Type 1 Ammonia CBC Glucose Orotic Acid Plasma Amino Acids Plasma Organic Acids Urine Amino Acids Urine Organic Acids

Plasma Amino Acids

Select the best metabolic lab test to investigate the following metabolic disease. A lab test may be chosen more than once. MSUD Ammonia CBC Glucose Orotic Acid Plasma Amino Acids Plasma Organic Acids Urine Amino Acids Urine Organic Acids

Plasma Amino Acids

A 2 year old is found comatose in her crib in the morning by her mother. Her mother can not revive her. Last night she had a mild vomiting illness and fed poorly during the day. She is brought to the ER and her blood sugar is 25 and the urinalysis shows no ketones. What metabolic test will most likely show the diagnosis? Plasma amino acids Plasma acylcarnitine Plasma carnitine Urine organic acids Urine acylglycine

Plasma acylcarnitine

A 2 year old is found comatose in her crib in the morning by her mother. Her mother can not revive her. Last night she had a mild vomiting illness and fed poorly during the day. She is brought to the ER and her blood sugar is 25 and the urinalysis shows no ketones. What metabolic test with be most likely to show the diagnosis? Plasma amino acids Plasma acylcarnitine Plasma carnitine Urine organic acids Urine acylglycine

Plasma acylcarnitine

When considering PA, MMA and GA1, the ultimate common component of chronic treatment includes: Preventting the body from becomeing catabolic (i.e. no fasting) High dose carnitine Low sugar diet sick day protocols IV dextrose fluide (D10) High dose IV carnitine Liver transplant

Preventting the body from becomeing catabolic (i.e. no fasting)

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. Someone with MCAD Deficiency can't break down medium chain fatty acids. Under stress, the body then can become hypoglycemic. This clinical presentation is because of a: Substrate accumulation Byproduct accumulation Product deficiency

Product deficiency

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. Someone with untreated PKU has decreased pigmentation because of a Substrate accumulation Byproduct accumulation Product deficiency

Product deficiency

Hyperammonemia can occur for many reasons. Which metabolic disease would you expect to see hyperammonemia and an greatly elevated anion gap when critically ill? OTC Deficiency Citrullinemia type 1 Tyrosinemia Proprionic Acidemia

Proprionic Acidemia

The urea cycle is the continuation of metabolism of: Fats Sugar Protein

Protein

A baby's newborn screen shows an elevated C14:1. The baby is at risk for all of the following problems EXCEPT: Hypoketotic hypoglycemia Pulmonary fibrosis Cardiomyopathy Sudden infant death syndrome (SIDS) Liver dysfunction

Pulmonary fibrosis

Several metabolic disease present with similar clinical picture. Match the disorder with its possible clinical presentation if not treated. Methylmalonic Acidemia Developmental Delay with no acute decompensation Recurrent episodes of vomiting and lethargy with mild illness

Recurrent episodes of vomiting and lethargy with mild illness

Several metabolic disease present with similar clinical picture. Match the disorder with its possible clinical presentation if not treated. OTC Developmental Delay with no acute decompensation Recurrent episodes of vomiting and lethargy with mild illness

Recurrent episodes of vomiting and lethargy with mild illness

Several metabolic disease present with similar clinical picture. Match the disorder with its possible clinical presentation if not treated. Proprionic Acidemia Developmental Delay with no acute decompensation Recurrent episodes of vomiting and lethargy with mild illness

Recurrent episodes of vomiting and lethargy with mild illness

Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild that includes the following diseases EXCEPT _________. Zellweger neonatal adrenoleukodystrophy [NALD] infantile Refsum disease [IRD] Refsum disease

Refsum disease

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are due to different defects within the same metabolic pathway. As such, there can be significant overlap in the clinical presentation, with the exception on one defining feature. Match that feature to the disease. MMA Cardiomyopathy Renal disease

Renal disease

A 5 year old male presents with intellectual disability, speech delay, movement disorder, and seizures. Brain MRI shows cerebral atrophy and a MRS shows a low creatine peak. Urine metabolites are checked and show an elevated creatine:creatinine ratio. Which condition should you suspect? OTC (Ornithine transcarbamylase deficiency) GAMT (Guanidinoacetate methyltransferase) deficiency AGAT (Arginine : glycine amidinotransferase) deficiency SLC6A8 (creatine transporter) deficiency

SLC6A8 (creatine transporter) deficiency

All types of mucopolysaccharidoses (MPS) disease exhibit dysostosis multiplex to a greater or lesser degree. Of the following diseases, which one has this skeletal finding but to a lesser degree and instead it is notable for behavioral and neurological problems? Hurler Maroteaux-Lamy Hunter Sanfilippo Morquio

Sanfilippo

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once Regression of skills, behavioral concerns, sleep disturbance, course facies, limited skeleletal findings Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Sanfilippo (MPSIIIA)

Which disorder is an example of locus heterogenity? Tay Sachs Disease Niemann Pick A Disease Sanfilippo Syndrome

Sanfilippo Syndrome

Match the biochemical findings with the clinical presentation. Clinical presentations listed may be classical or non-classical. (Use each answer once) Urine organic acids - propinylglycine, methylcitric acid, tigylglycine, 3-hydroxypropionic acid Child with with onset of dystonia after fever and illness Teenage with intellectual disability and renal insufficiency School age Amish child with cardiomyopathy

School age Amish child with cardiomyopathy

A 10 year old girl with Phenylketonuria comes to clinic for routine follow-up. She is not on diet and has an average phenylalanine level of 12 mg/dl. Which of the following statements is false? She should restart diet She is considered a hyperphenylalaninemia and does not require treatment. She should be offered Sapropterin dihydrochloride (Kuvan), as this might help reduce her Phe levels . At this level, maternal PKU syndrome will be a concern in the future.

She is considered a hyperphenylalaninemia and does not require treatment.

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. In someone with Pompe disease, the enzyme (α-glucosidase (GAA)) is not functional and so glycogen is not broken down which leads to health problems. This is an example of Substrate accumulation Byproduct accumulation Product deficiency

Substrate accumulation

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. Someone with untreated PKU has cognitive impairment because of a Substrate accumulation Byproduct accumulation Product deficiency

Substrate accumulation

Dr. Held provided a quick overview of several metabolic diseases. Taking our favorite simplistic view of metabolism and putting it to practice with real life examples, match the following statement with the reason. Reasons are used more than once. argininosuccinic acid lyase deficiency, which is a type of urea cycle disorder, presents with overwhelming illness and encephalopathy in the neonate because of high ammonia. This is because of a Substrate accumulation Byproduct accumulation Product deficiency

Substrate accumulation

Match the lysosomal storage disorder to the best description of the clinical presentation. Diseases are used only once Cherry red spot, exaggerated startle reflex, developmental regression Fabry Gaucher Disease Hunter Disease (MPS II) Hurler Disease (MPS I) Krabbe Nieman Pick A San filippo (MPSIIIA) Tay Sachs disease

Tay Sachs disease

Enzyme replacement therapy (ERT) is available as an FDA-approved drug for all of the following disorders EXCEPT: Gaucher disease Fabry disease Pompe disease Tay Sachs syndrome Hurler (MPS I) syndrome

Tay Sachs syndrome

Match the biochemical findings with the clinical presentation. Clinical presentations listed may be classical or non-classical. (Use each answer once) Urine organic acids - methylmalonic acid, propinylglycine, methylcitric acid, tigylglycine, 3-hydroxypropionic acid Child with with onset of dystonia after fever and illness Teenage with intellectual disability and renal insufficiency School age Amish child with cardiomyopathy

Teenage with intellectual disability and renal insufficiency

What causes the spectrum of severity within the Zellweger Spectrum Disorders (ZSD) The amount of functioning peroxisome The buildup of toxic substrate within the peroxisome A deficit of energy due to lack of b-oxidation of VLCFA

The amount of functioning peroxisome

Which of the following presentations is/are consistent with ornithine transcarbamylase deficiency: Infant male in hyperammonemic coma Toddler male with chronic vomiting Women with mental status changes postpartum Infant female in hyperammonemic coma Elderly male with mental status changes after prolong fast following bowel surgery These can all be presentations of someone with OTC.

These can all be presentations of someone with OTC.

A patient with mitochondrial disease has a mutant load of 10% in the eyes. He has vision loss. He has a mutant load of 60% in the stomach, but does not have any clinical symptoms of disease related to this mutant load. This disease presentation (or lack there of) is an example of: Threshold Effect Bottleneck Heteroplasmy Maternal Inheritance

Threshold Effect

What feature of mtDNA contributes to the commonly observed inter-family variability associated with mitochondrial disorders? Recombination Threshold effect of heteroplasmy Maternal inheritance High mutation rate relative to nuclear DNA

Threshold effect of heteroplasmy

In those with a diagnosis of PKU, ____________ is considered a conditionally essential amino acid (e.g. an amino acid where normal synthesis can be limited under special pathophysiological conditions). Arg Tyr Gly Cys Val Asn

Tyr

A 6 year old girl has mild coarsening of her facial features and mild enlargement of the liver. She has developed ADHD and sleep problems over the last 9 months. You suspect Sanfilippo syndrome but are not certain and think that there may be other conditions with similar overlap. If you could only start with one test, which one might you consider as an initial screen? Urine MPS (mucopolysacharides) screen. Urine Organic Acids DNA testing for the SGSH gene associated with Sanfilippo Urine amino acids Urine Hex A enzyme

Urine MPS (mucopolysacharides) screen.

Which disorder of fatty acid oxidation has the most severe presentation? SCADD VLCADD MCADD

VLCADD

The Duarte variant is thought to be benign, yet its presence with a different allele can cause a decrease in the GALT enzyme activity. Match the approximate GALT enzyme activity with the specific combinations below. Options are used only once. W= working copy of GALT gene D= Duarte change G= Galactosemia causing change (i.e. severe mutation) W/W D/W D/D D/G G/G 100% 75% 50% 5-25% 0%

W/W 100% D/W 75% D/D 50% D/G 5-25% G/G 0%

Plasmalogens and phytanic acid levels are used when checking for: A disorder of creatine biosynthesis. a peroxisomal biogenesis disorder.

a peroxisomal biogenesis disorder.