Inherited Neurodegenerative Disorders

Question 1

Tay-Sachs Disease

Answer 1

Metabolic defect: hexosaminidase A
Chromosome and inheritance: 15, autosomal recessive
Notes: Cherry-red spots. More common in Ashkenazi Jews

Question 2

Niemann-Pick Disease

Answer 2

Metabolic defect: sphingomyelinase
Chromosome and inheritance: 11, autosomal recessive
Notes: Cherry-red spot. More common in Ashkenazi Jews

Question 3

Gaucher Disease

Answer 3

Metabolic defect: glucocerebrosidase
Chromosome and inheritance: 1, autosomal recessive
Notes: Cherry-red spot. Gaucher cells in bone marrow

Question 4

Krabbe Disease

Answer 4

Metabolic defect: Galactosylceramide P-galactosidase
Chromosome and inheritance: 14, autosomal recessive
Notes: Globoid cells with periodic-acid Schiff (PAS)-positive granules

Question 5

Hurler’s Syndrome

Answer 5

Metabolic defect: a-L-iduronidase
Chromosome and inheritance: 4, autosomal recessive
Notes: Clouding of the cornea, Characteristic facies and dwarfism

Question 6

Hunter’s Syndrome

Answer 6

Metabolic defect: Iduronate sulfatase
Chromosome and inheritance: X-linked
Notes: Characteristic facies and dwarfism (no corneal clouding)

Question 7

Metachromatic leukodystrophy

Answer 7

Metabolic defect: Arylsulfatase A
Chromosome and inheritance: 22, AR
Notes: Cherry-red spot. Demyelinating disorder. Can present as schizophrenia in adults. Positive urine sulfatides

Question 8

Adrenoleukodystrophy

Answer 8

Metabolic Defect: Very long chain FAO
Chromosome and inheritance: X-linked
Notes: White matter hyperintensity on MRI. May present as a neuropathy or myelopathy in adults

Question 9

Alexander disease

Answer 9

Metabolic Defect: Glial fibrillary acidic protein
Chromosome and inheritance: 11 or 17, AR
Notes: rosenthal fibers on biopsy, macrocephaly, dysmyelination of the CNS

Question 10

Canavan Disease

Answer 10

Metabolic defect: Aspartoacylase
Chromosome and inheritance: 17, autosomal recessive
Notes: Macrocephaly, dysmyelination of the CNS

Question 11

Pelizaeus-Merzbacher disease

Answer 11

Metabolic defect: proteolipid protein
Chromosome and inheritance: X-linked
Notes: Pendular nystagmus, dysmyelination of the CNS

Question 12

Leigh disease

Answer 12

Metabolic defect: mitochondrial
Chromsome and inheritance: AR or X-linked
Notes: bilateral putaminal hyperintensity on MRI

Question 13

Neuronal Ceroid lipofuscusinosis

Answer 13

Metabolic defect: excess lipofuscin storage
Chromosome and inheritance: variety
Notes: dementia, myoclonus, ataxia, retinitis pigmentosa. Variety of forms with diff ages of onsets and severities