lipid storage diseases

what diseases can be categorized into sphingolipidoses?

Niemann-Pick, Fabry, Krabbe, Gaucher, Tay-Sach, metachromatic leukodystrophy, multiple sulfatase deficiency, and Farber disease

what is Sandhoff disease (variant AB)

severe tay-sach; 6 month onset, no ethnic specificity; deterioration CNS, motor weakness, early blindness, spasticity, seizure, macrocephaly, cherry red spots; no treatment; keep airway open and proper nutrition; children die by 3 from respiratory infections

what is the severe subtype of GM1 gangliosidosis?

shortly after birth, neurodegeneration, seizures, liver/spleen enlargement, facial features, skeletal irregularities; typically get cherry red spots

what are the signs and symptoms of tay sach?

strong response to sudden noise (startle response), muscle stiffness; variant forms loss motor skills, increased startle reaction, macular pallor, cherry red spots

what chromosome is HEXA on?

15, codes for hexosaminidase A; more common in Ashkenazi Jews, Cajuns, and French Canadians

what are the subtypes of Gaucher disease?

I (adult/ non- neuronopathic, most common, asymptomatic, skeletal weakness, easy bruising, Ashkenazi Jews) II (acute infantile neuropathic): within 3 months birth, fatal by 2 years; dementia, spastic, seizure, limbs rigid, hepatosplenomegaly III: chronic, birth

what is the pathophysiology of Gaucher disease?

accumulate histiocytes (fibrillar, blue gray cytoplasm that is crinkled; small nucleus with coarse chromatin and indistinct nucleolus)

what is Farber's disease (farber's lipogranulomatosis)?

accumulation fatty material in joints, tissue, and CNS; deficiency of ceramidase enzyme; affects males and females and onset is early or late

what is Type C Niemann-Pick?

appear early or late; caused by lack of NPC1 or NPC2 proteins; cholesterol accumulation inside nerve cells (malfunction); inability to look up and down, difficulty walking/swallowing

what is late infantile GM1 gangliosidosis?

between age 1-3; neurological symptoms like ataxia, seizures, dementia, and speech difficulty

what is the diagnosis of tay sach?

cherry red spots, determination of b HEXA isolated in leukocytes, degeneration of brain tissue cytology; prenatal screening by amniocentesis

what are the signs and symptoms of Faber's disease?

death by age 2; neurological symptoms in first few weeks (lethargy, difficulty swallowing), joint contractures, vomiting, arthritis, swollen joints, nodes under skin which thicken around joints with progression; more severe liver/spleen diagnosed soon after birth and death by 6 months

what is Gaucher disease?

deficiency of GBA = accumulation undergraded glycolipid in form of glucosyl ceramide in reticuloendothelial system cells; mutations for lysosomal hydrolase, transporter proteins

what is GM2 gangliosidoses?

deficiency of HEXA (a and b subunits); symptoms begin first 6 months of life including loss mental ability, dementia, CHERRY RED SPOTS IN RETINA, decreased eye contact, loss hearing; death by age 4

what are GM1 ganlgiosidoses ?

deficiency of beta-galactosidase; 3 presentations:

what is GM1 gangliosidosis?

develop between 3-30; muscle atrophy, neurological complications (less severe), sustained muscle contractions (twisting and repetitive movements or dystonia [abnormal posture]); angiokeratomas may develop on lower trunk and hepatosplenomegaly

what are lipid storage diseases?

diseases that arise from deficiency of specific lysosomal hydrolase with resulting accumulation of the enzyme's specific substrate; autosomal recessive except Fabry's

what do patients die from the Fabry disease?

heart, kidney, or stroke complications

What is Niemann-Pick disease?

impaired degradation of sphingomyelins due to deficiency of spingomyelinase enzyme (SMPD1 gene); accumulation sphingomyelin in liver, spleen, bone marrow, brain; ataxia, eye paralysis, spasticity, cherry red spot (50% patients)

what are the types of Tay Sachs?

infantile (6 months after birth, GM2, deteriorate mental abilities, can become deaf, atrophied, death before 4) juvenile (rate, 2-10, deterioration, dysphagia, ataxia, spastic, death before 15) late (30-40 onset, gait, neurological deterioration, spastic, cognitive decline)

what pathology and clinical manifestation is associated with Niemann-Pick?

large macrophages with foamy cytoplasm and sea blue histiocytes; hepatosplenomegaly, reduced appetite, dysphagia, abdominal distension, pain, thrombocytopenia

what is Krabbe disease (globoid cell leukodystrophy/galactosylceramide lipidosis)?

mutation of GALC (14q21) and deficiency of galactocerebrosidase; buildup fat --> demyelination --> deterioration mental / motor skills; myoclonic seizures; enzyme test diagnosis; fatal before age 2

what are the signs and symptoms of Fabry disease?

neurological signs (burning pain in arms and legs, worsens in hot weather or after exercise), buildup excess material in cornea (cornea verticillate), blood vessel thickening (impaired circulation), heart enlargement, angiokeratoma (red-purple spots on skin)

what is Fabry disease?

rare, X-LINKED lysosomal storage disease caused by mutation in the gene that encodes alpha-galactosidase; multisystem; accumulation of glycosphingolipids in vasculature of renal glomeruli, coronary arteries, cardiac myocytes and cardiac conduction system; primarily male affected