Lysosomal Storage Disorders

Question 0

GCL (globoid cell leukodystrophy)

Answer 0

aka Krabbe Disease
GALC (galactocerebrosidase) deficiency
galactosylsphingosine accumulates in lysosomes

Question 1

MLD (metachromatic leukokdystrophy)

Answer 1

defect in arylsulfatase A
can’t convert sulfatides into ceramides
sulfatides accumulate in lysosomes

Question 2

MPS 1

Answer 2

aka Hurler Syndrome
alpha-L-iduronidase deficiency
Sx: facial dysmorphism, HSM, cataracts, CMP, dysostosis multiplex, neurologic decline, pulm dz
Tx: ERT but doesn’t cross BBB so doesn’t help neuro sx
Stem cell transplant s/t helps- if so prevents neuro sx

Question 3

MPS 2

Answer 3

aka Hunter Syndrome
iduronate-2-sulfatase deficiency
*X-linked
Sx: facial dysmorphism, airway obstruction, skeletal deformity, CMP, neuro decline
     *no cataracts
Tx: ERT but doesn't cross BBB

Question 4

Gaucher Disease

Answer 4

Acid beta-glucosidase deficiency
*Ashkenazi Jews
Sx: HSM, cytopenia, skeletal dz
Diagnosis: large blue histiocytes on BMBx (Gaucher cells)
Tx: ERT

Question 5

Fabry Disease

Answer 5

alpha-galactosidase deficiency
*X-linked
Renal: glomerular sclerosis, tubular atrophy, interstitial fibrosis
GI: achalasia, emesis
Cardiac: LV dysfunction, atherosclerosis
Neuro: decreased sweating, acroparesthesia, pain crises, stroke
Tx: ERT
Prognosis: M live 50yr w/o tx, F variable affected

Question 6

Neimann-Pick Disease

Answer 6

acid sphingomyelinase deficiency
*Ashkenazi Jews
Sx: FTT, HSM, resp abnl, neuro deterioration
*macular cherry red spot
Diagnosis: sea-blue histiocytosis on BMBx
Tx: supportive

Question 7

Tay-Sachs Disease

Answer 7

hexosaminidase A deficiency
*Ashkenazi Jews
Sx: nl at birth
macular cherry red spot as early as 3mos
hypotonia, developmental regression ~6mos
spasticity, blindness, szrs, macrocephaly by 1yo
Tx: supportive
Prognosis: live only 3-4yrs