0521779407-13 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:15
938 Lysosomal Diseases■Abdomen: hepatosplenomegaly (Niemann-Pick, Tay-Sachs/
Sandhoff disease/GM2, Gaucher disease [esp. spleen])
■Neurological: eye movements (gaze palsies: Gaucher disease,
Niemann-Pick, nystagmus: Niemann-Pick, GM1), spasticity, rigid-
ity (Gaucher disease, Krabbe, metachromatic leukodystophy, late
Tay-Sachs/Sandhoff disease/GM2, GM1), hypotonia (GM1, Tay-
Sachs/Sandhoff disease/GM2), areflexia (Krabbe, Metachromatic
leukodystophy, GM1, late-onset Tay-Sachs/Sandhoff disease/GM2),
strokes (Fabry disease)
■Skeletal: degenerative changes (Gaucher disease, GM1), limb defor-
mities (Krabbe)
■Eye: optic atrophy, macular changes (cherry red spot: Niemann-Pick,
Tay-Sachs/Sandhoff disease/GM2, Krabbe), corneal opacities (Fabry
disease), blindness (neuronal ceroid lipofucinosis/Batten disease),
gaze palsy (Gaucher disease)
■Skin: telangectasias, hypohydrosis (Fabry disease)
■Genitourinary: renal failure (Fabry disease)
tests
Laboratory
■basic blood studies:
Very long chain fatty acids
➣Specific enzyme tests on WBCs, skin fibroblasts (see “Differential
Diagnosis”)
➣WBCs for electron microscopy (lysosomal inclusions)
➣increased acid phosphatase (Gaucher disease)
➣CBC (pancytopenia: Gaucher disease, vacuolated lymphocytes:
GM1)
■basic urine studies:
➣Sialic acid, oligosaccharides, sulfatides
Other Tests
■Bone marrow: foamy macrophages (Farber disease, Niemann-Pick),
sea blue histiocytes (Gaucher disease)
■CSF: increased protein (metachromatic leukodystophy)
Imaging
■MRI: white matter changes (Krabbe, metachromatic leukodystophy)
■Bone survey: bone thinning, diaphyseal splaying, vertebral changes,
lytic lesions (Sialidosis, Gaucher disease, GM1)
differential diagnosis
■Examples of lysosomal disorders: “Name [Enzyme defect]”
■Cystinosis [cysteine transporter]