Lysosomal Storage Diseases Flashcards
Fabry Disease
Sphingolipidose a-Galactosidase deficient => ceramide trihexoside accumulates Peripheral neuropathy of hands and feet Angiokeratomas CV/renal disease => strokes Cataracts Usually survive to adulthood
Gaucher Disease
Sphingolipidose
d-Glucocerebrosidase missing => glucocerebroside accumulates
Bone involvement => aseptic necrosis of femur, bone crises
HSM
Anemia, thrombocytopenia, MR
Niemann-Pick Disease
Sphingolipidose Sphingomyelinase deficient => sphingomyelin accumulates Progressive neurodegeneration HSM Cherry-red spot on macula Foam macrophages in bone marrow
Tay-Sachs Disease
Sphingolipidose
Hexosaminidase A deficient => GM2 ganglioside accumulates
Death by 3 years
Progressive neurodegeneration, developmental delay, microcephaly
Cherry-red spot on macula
Lysozymes with onion skin
Krabbe Disease
Sphingolipidose B-Galactosidase missing => Galactocerebroside accumulate Death by 2 years Peripheraly neuropathy Developmental delay Optic atrophy Decerebrate posturing Bone marrow transplant?
Metachromatic leukodystrophy
Sphingolipidose
Arylsulfatase A missing => cerebroside sulfate accumulates
Rarely manifests before 6 months
Central and peripheral demyelination = ataxia, dementia
Hurler Syndrome
Mucopolysaccharidose
a-L-iduronidase missing => heparan sulfate and dermatan sulfate accumulation
Most common => onset 1 year, death by 14
Developmental delay, coarse facial features with enlarged forehead
Corneal clouding, enlarged tongue, airway obstruction
Hunter Syndrome
Mucopolysaccharidose
Iduronate sulfatase missing => Heparan sulfate and dermatan sulfate accumulate
X-linked recessive
Like Hurler but milder with longer survival
No corneal clouding
Sanfilippo Syndrome
Mucopolysaccharidose Heparan-N-Sulfatase missing => heparan sulfate accumulates Developmental delay => severe MR Onset in preschool, death in midteens Little somatic change
Morquio Syndrome
Mucopolysaccharidose Keratan sulfate accumulates Diagnosis by age 2 Skeletal deformities, corneal clouding No mental abnormalities Death due to atlantoaxial instability => minor trauma to spinal cord
Maroteaux-Lamy Syndrome
Mucopolysaccharidose
N-acetylhexosamine-4-sulfatase missing => dermatan sulfate accumulates
Multisystemic disesae, spares CNS
General effect of accumulation of GAGs
Skeletal deformities => coarse facial features
Corneal clouding, CV disease (valvulopathies), excessive hair
Heparan sulfate accumulating particularly deleterious to…
Nervous tissue => causes cognitive defects
Keratan suflate accumulating particularly deleterious to…
Corneal and cartilaginous tissue, spares brain
