SDL Quiz

what drug helps relieve carnitine deficiency

levocarnitine

von-elevated TAGS

excess pyruvate is converted to acetyl Coa which can be used to make fatty acids glyceralehyde excess (from glycolysis) can also be used to make glycerol from glycerol 3 phosphatase these two combine to form TAG's

MSUD- phenotype

failure to thrive, seizures, irritability, little interest in feeding

carnitine deficiency- why hepatomegaly, why low ketone bodiesm hyperammonemia

fatty acids being transported to the liver during fasting for FA oxidation build up in the liver cells because they are unable to be oxidized no FA oxidation-no production of ketone bodies patient is breaking down amino acids to produce energy in the fasting state as an alternative to FA oxidation resulting in higher output of ammonia

what key features of achondroplasia would be seen in an ultrasound

frontal bossing, macrocephaly, short femur length

VCLFAD- intermittant hypoglycemia, hepatomegaly

if the body is in starvation mode and oxidizes s/m chain fatty acids, it will be unable to oxidize vlc and therefore unable to produce glucose these unoxidized vlcfa are sent to the liver where they accumulate since they cannot be oxidizes in liver perioxisomes

what diet for angelman should be used to manage the seizures

keto

how does coronary artery disease increase in patients with familial hyper

oxidized LDL hanging out in the arteries and unable to enter the cells are taken up by SRA receptors on macrophages, these cells accumulate to form foam cells. these foam cells can eventually create a plaque within the arteries

Management of disorder

PT/OT/ST; behavioral programs/care

causative gene for achondroplasia- what chromosome, location, function

FGFR3 4 P16 -tyrosine kinase receptor that binds to fibroblast growth factors and triggers signaling cascades in this disorder= FGF unable to bind to receptor leading to uncontrolled/uncoordinated processes in the bone growth plates=stunted growth

what gene causes von gierke disease, where is it located, inheritance

G6PC1 chromosome 17 glucose-6-phophatase AR

advantage to having high HDL in patients with hyperchol

HDL can take up cholesterol and return it to the liver to be processed, increased HDL will decrease the amount of cholesterol circulating

tay sachs- gene, structure of protein, organelle affected, what accumulates

HEXA, two domains/heterodimer w alpha/beta subunit, GM2 gangliosides AR

beckman weidemann syndrome overview

IGF2 (maternal imprinting), CDKN1C (paternal imprinting) get by: methylation at maternal Ic1 (activating IGF2), UPD paternal, mutation at maternal CDKN1C, demethylation at maternal IC2 (inactivating CDKN1C) -macroglossia, macrosomia, omphalocele, hypoglycemia, ear creases/pits

Angelman Syndrome

slow growth, microcephalic, autism like, jerky movements, happy and laughs a lot

why do statins not work in patients with familial hypercholesteolemia

statins work to stop the production of cholesterol but that is not the issue in these patients, these medications wont reduce the amount of LDL in the patient's blood

methyl malonic- what action should physician take according to american college of medical genetics algorithm

test- urine Orangic acids, plasma Acylcarnitine

what does TAGS in the normal limits indicate

there is not an issue with TAG breakdown so can rule out lipoprotein lipase disorder, VLDL disorder

why would a Y-specific primer sequencing report be done in patients with turners what would a negative test indicate?

to see if the child has mosaicism in which some cells have the 46XY karyotype patient is not at risk for gonadal blastoma which occurs in mosaic patients

edema of feet, redundant skin on back of neck, small, dont go into puberty, girls, ovarian dysgenesis

turners syndrome one X chromosome or isochromosome x

otc- urine uracil levels

would be high- orotic acid can be converted to uracil via ump synthase

von gierke disease type 1a phenotype

-abdominal distension -irritability -doll like face, round cheeks -thin extremities -malnourished/emaciated

biochem mechanism for patients with familial hyperchol

-absence of LDL receptors -altered LDL receptors that cant bind LDL -B100 protein defect that makes LDL unable to bind with the cell to be taken in

what prenatal test are preformed to assess for down syndrome, name all of the test that could diagnose this condition

-chorionic villus sampling -aminocentesis -karyotype g-banding, array CGH, SNP array, FISH

what are therapies and psychosocial supports for children with turners

-growth hormone administration -estrogen for secondary sex characteristics

ways to get angelman

-maternal deletion -UBE3A mutation -paternal UPD -imprinting defect where maternal is silenced also

a women is having spontaneous abortions and the test reveals the fetus has monsomy 21, explain

-monosomy 21 is not typically compatible with life -woman is having non-disjunction within the gametes with chromosome 21

huntingtons- expansion fragile x friedreich ataxia spinocerebrallar ataxia myotonic dystrophy type 1 and 2

1. CAG repeat in exons- 9-35 normal, 40+ HD 2. CGG in 5UTR FMR1 gene 3. AR, FRDA, GAA repeat intron 4. ATXN1, CAG repeat 5. DMPK, CTG repeat 50-100 mild, over 1000, c.19; CNBP, CCTG 75 repeats, c.3

MSUD variations- 1. classic severe 2. intermediate 3. intermittent 4. thiamine-responsive

1. death by 3 months of age, not responsive to treatment 2. responsive to controlled diet, severe developmental and neurological delay 3. controlled diet, actue episodes of ataxia lethargy, semi coma 4. total cute in response to thiamine

pharm intervention for familial hyper-primary and secondary

1. ezemtimibe-limits absorption of cholesterol (typically combined with statins to keep cholesterol levels low) 2. PCSK9 inhibitors- help liver absorb more cholesterol lowering the amount circling in the blood 1. bile acid sequestrits- block bile acid absorption from the stomach (allows cholesterol attached to be excreted rather than reabsorbed) 2. niacin/nicotinic (decreases FFA release) can raise HDL and lower LDL

gene for VLCFAD, inheritance pattern,

ACADVL, AR

what influences the development of downs syndrome

AMA

genes defective in familial hyper, homozygote versus heterozygote

APOB gene, LDLR gene, PCSK9 homo can have a worse manifestation with heart attacks in childhood heterozygotes have better outlook

carnitine deficiency- inheritance, gene

AR OCTN2- SLC22A5

maple syrup urine disease-gene, inheritance, mechanism

BCKDHa/b- branched chain alphaketo dehydrogenase -trouble metabolizing branched AA- leucine, isoleucine, valine AR

angelman- chromosome, location/gene, how disease comes about

CNV on chromosome 15q11-13, acrocentric, long arm-q UBE3A- mutation leads to disruption in ub protein degradation paternal imprinted, maternal

methyl malonic- gene, variant, present, inheritance

MMA AR missense vomiting, sleeping a lot, dehydrated, acidosis, not gaining weight high forehead, broad nasal bridge, wide appearing eyes, long smooth philtrum

prader willi overview

SNURF gene maternal imprinted, paternal expressed hypotonia, obesity, impaired satiety, failure to thrive

carnitine deficiency symptoms

abdominal pain, vomiting, myotonia, muscle weakness

methyl malonic- ACT SHEET for physicians

ascertain current clinical status, consult pediatric metabolic specialists' same day, evaluate newborn for serious conditions and transfer to hospital if needed, confirm diagnostic testing, provide family with basic information regarding the disorder

in what populations is tay sachs disease high

ashkenazi jews, french canadians, cajun

OTC- why glutamine levels high, inheritance patttern

body is acidic (excess ammonia)- packs up NH3 and glutamate to make glutamine and transports kidney who use glutaminase to release NH3 and glutamate, nh3 then neutralizes some acid by combing to form NH4 which is then excreted x-linked dominant

hypoglycemia in carnitine deficiency

cannot transport acetly coa into mitochondria- aka fatty acid oxidation (which is providing fuel for gluconeogenesis) is blocked

tay sachs phenotype

cherry red macula, psychomotor degeneration, seizures, hypotonia, dementia, increased startle response

pathway affected by methylmalonic aciduria

cobalmin is unable to enter mitochondria and be converted to its active form and used as a coenzyme for methyl malonyl-coa mutase, therefore methylmalonyl cannot be converted to propionyl COA

what surveillance should be done for someone with downs syndrome

congenital heart defects, leukemia, hypothyroidism, hearing loss, spinal cord injuries, developmental/intellectual disabilities, improper growth, respiratory infections

besides achondroplasia-what other disorders are associated with variants in the FGFR3 gene

crouzon syndrome, LADD syndrome, muenke syndrome, SADDAN, hypochondroplasia, thanatophoric dysplasia types 1/2

methylmalon- nutritional guidelines, nutrients/medicine for condition

decrease intake of amino acids/odd chain number FA vitamin b12- hydroxycobalamin -active form of B12

clinical presentation of downs

depressed nose, up slanting palpebral fissures, small ears, short neck, short broad hands/feet

turners and chronic disease

elevated chance of patient developing T2D-must work to prevent/manage this disease in these patients since they are already at risk for CD issues

methylmalonic aciduria NBS secreening

elevated propionyl CA

silver russell overview

get by: maternal UPD, demethyl at paternal IG1 (turn off IGF2), -small for age, body asymmetry, feeding difficulties,

what would you expect to find on a histological slide of a patient with turners syndrome

gonadal dysgenesis- streaks of CT instead of ovaries

methyl malon- main complications for long term surviving patients

growth delay, ID, kidney disease, pancreatitis

von- elevated serum lactic acid/elevated pyruvate

high G6p sends it back down glycolysis producing lots of pyruvate which is then shunted to lactate

von- elevated uric acid levels

high action in pentose phosphate pathway leading to de novo synthesis of purine nucleotides which are not needed and are catabolized to uric acid

von gierke explanation- low fasting blood glucose

liver and kidney unable to convert glucose 6p to glucose to be transmitted into the blood to be used my muscle during times of fasting

nutritional treatment for vlcfa

low fat diet, inclusion of odd chain FA in diet, injection of IV glucose, triheptanoin (medium odd chain fatty acid supplement as a source of FA's and calories)

what key prenatal signs should you look for on an ultrasound that would lead to turners

lymphedema, hydrops, heart/kindey defects

best way to manage von gierke, why does this disease occur in fasted state

maintain normal blood glucose concentration body cannot complete glycogenolysis or gluconeogenesis

methylmalonic acidemia- involved with what

methyl malonic acid is an intermediate in the catabolism of methionine, isoleucine, valine, threonine, and odd chain FA form propionyl CA to methyl manoyl to succinyl Coa

most commo pathogenic variant for achondroplasia, how does one normally get it

missense- C1138G>A mostly de novo, paternal age effects, AD- dominant version is lethal

huntingtons disease, inheritance pattern, gene, location, what type

neurological decline, cortex degeneration, personality changes, motor abnormalities, hyperreflexia, dementia autosomal dominant, typically paternally transmitted, GOF HTT, chromosome 4p16.3, submetacentric

does maternal age contribute to a child being born with turners

no, a majority of turners patients are caused by absence of paternal X

how does downs arise what chromosome and what type of chromosome is this

non disjunction in meiosis one (homologous chromosomes fail to separate) or two (sisters fail to separate), translocation chromosome 21-acrocentric (13-14, 21/22) metacentric- 1,3,16,19,20

why would a turners syndrome patient be short

only one copy of the SHOX gene

two medications for OTC- hyperammonia treatmentq

phenylbutrye- binds glutamine benzoate- binds glycine both fast track to liver to excret excess ammonmium- can bypass urea cycle

turners- more live births or prenatal losses

prenatal losses

Huntington's and HTT gene mechanism

protein assists with mRNA moving/transcription/translation- gain of function so increases and aggregates protein leading to issues with proper transport and maturation of proteins