Inherited Metabolic Diseases Of The NS

Question 1

Hallmark of all hereditary metabolic diseases

Answer 1

Psychosensorimotor regression

Question 2

Gaucher cell

Answer 2

20-60um histiocyte with wrinkled appearance of the cytoplasm eccentric nucleus
Found in marrow, lungs and other viscera

Question 3

This should be suspected in an infant with the facial features of mucopolysaccharidosis and severe early-onset neurologic abnormalities

Answer 3

Infantile Generalized GM1 gangliosidosis or Beta-Galactosidase Deficiency or GLB1 mutation

Question 4

Niemann-Pick cells

Answer 4

Foamy histiocytes containing sphingomyelin (+cholesterol if in viscera)

Question 5

Globoid cells

Answer 5

Seen in Globoid Cell Leukodystrophy (GALC Mutation), large histiocytes containing psychosine, a toxic metabolite of galactocerebroside

Question 6

Only 2 Leukodystrophies in which nystagmus had been an invariable finding

Answer 6

1. Pelizaeus-Merzbacher Disease (PLP1 Mutation)

2. Cockayne Syndrome

Question 7

This leukodystrophy can be treated by transplant of HLA-matched umbilical cord hematopoietic cells in asymptomatic babies + substantial antirejection medication

Answer 7

Globoid Cell Leukodystrophy (Krabbe Disease, Galactocerebrosidase Deficiency, GALC Mutation)

Question 8

A Leukodystrophy with behavioral regression, enlarging head, characteristic MRI of diffuse uneven high signal intensity on T2, and marked elevation of urinary NAA (N-acetyl-L-aspartic Acid)

Answer 8

Spongy degeneration of Infancy (Canavan-van Bogaert-Bertrand or Canavan disease)

Question 9

Autosomal recessive disease characterized by stippled, irregular calcifications of the patellae and greater trochanters

Answer 9

Cerebrohepatorenal Zellweger Disease

Question 10

Classic triad of trismus, strabismus and opisthotonus

Answer 10

Gaucher disease

Question 11

Macrocephaly (enlarging head without hydrocephalus) is seen the ff infantile inherited metabolic disorders

Answer 11

Canavan spongy degeneration of infancy
Tay-Sachs disease (some)
Alexander disease

Question 12

Infantile inherited metabolic disorder characterized by colorless, friable hair, that appear twisted under the microscope (pili torti)

Answer 12

Menkes Disease (aka Trichopoliodystrophy or ATP7A Mutation)

Question 13

Treatment for Menkes disease

Answer 13

Copper histidine SC BID

Must be started in the first weeks of life to permit normal neurodevelopment

Question 14

Infantile inherited metabolic disease that presents with opthalmic signs of bilateral cataracts, glaucoma, large eyes, megalocornea, bupthalmos, and blindness.

Answer 14

Oculocerebrorenal (Lowe) syndrome

OCRL1 mutation

Question 15

Autosomal disorder presenting in infancy with hoarse cry and characteristic periarticular and subcutaneous swellings and progressive arthropathy leading to ankylosis

Answer 15

Farber Disease (Lipogranulomatosis) 
ASAH1 Mutation
Or Ceramidase deficiency

Question 16

Rosenthal fibers

Answer 16

Eosinophilic hyaline bodies most prominent just below the pia and around blood vessels in the cortex brainstem spinal cord
Glial degradation product
Seen in Alexander Disease

Question 17

Inherited metabolic disorder/s with Dysmorphic facial features of depressed and wide nasal bridge, frontal bossing, hypertelorism, puffy eyelids, long upper lip, gingival and albeolar hypertrophy, macroglossia, low-set ears

Answer 17

Infantile Generalized GM1 Gangliosidosis

Mucopolysaccharidosis

Question 18

Infantile inherited metabolic disorders associated with cataracts

Answer 18

Galactosemia
Lowe disease
Zellweger disease

Question 19

The inherited Hyperammonemias are of the autosomal recessive pattern EXCEPT

Answer 19

Ornithine transcarbamylase deficiency - X-linked dominant

Question 20

This inherited Hyperammonemia presents with excessive dryness and brittleness of the hair (trichorrhexis nodosa)

Answer 20

Argininosuccinic aciduria

Question 21

Enzyme lacking in Maple Syrup Urine Disease?

What accumulates as a result?

Answer 21

Deficiency in alpha-keto acid dehydrogenase resulting in the accumulation of branched chain amino acids: leucine, isoleucine, valine

Question 22

Garrod’s cardinal principle of gene action

Answer 22

Genetic factors specify chemical reactions as well as biochemical individuality

Question 23

Level of serum phenylalanine which with phenylpyruvic acid in the urine, blood and CSF, is diagnostic of PKU

Answer 23

Above 15mg/dL

Question 24

Autosomal recessive amino acid disorder characterized by intermittent red scaly rash, episodic personality disorder and episodic cerebellar ataxia

Answer 24

Hartnup disease (SLC6A19 mutation)

Question 25

What is the only treatment shown to stabilize and reverse some of the MRI changes of Adrenoleukodystrophy?

Answer 25

Bone marrow transplantation

Question 26

Identified locus of the following mitochondrial disorders 
Leigh Disease
NARP
MERRF
MELAS

Answer 26

Leigh Disease locus 8993
NARP locus 8993
MERRF locus 8344
MELAS locus 3243

Question 27

Stain that allows visualization of subsarcolemmal and intermyofibrillar collections of membranous (mitochondrial) material in the type 1 (red) muscle fibers from which the ragged red fibers derive its name.

Answer 27

Gomori trichome stain

Question 28

The pathologic findings of Leigh disease resemble but are more extensive than that of Wernicke disease and spares this structure

Answer 28

Mammillary bodies

Question 29

The mutation resulting in the syndrome of Sensory NARP creates a defect in which mitochondrial/respiratory chain protein?

Answer 29

ATPase-6 of complex V