Inherited Metabolic Diseases Of The NS Flashcards
Hallmark of all hereditary metabolic diseases
Psychosensorimotor regression
Gaucher cell
20-60um histiocyte with wrinkled appearance of the cytoplasm eccentric nucleus
Found in marrow, lungs and other viscera
This should be suspected in an infant with the facial features of mucopolysaccharidosis and severe early-onset neurologic abnormalities
Infantile Generalized GM1 gangliosidosis or Beta-Galactosidase Deficiency or GLB1 mutation
Niemann-Pick cells
Foamy histiocytes containing sphingomyelin (+cholesterol if in viscera)
Globoid cells
Seen in Globoid Cell Leukodystrophy (GALC Mutation), large histiocytes containing psychosine, a toxic metabolite of galactocerebroside
Only 2 Leukodystrophies in which nystagmus had been an invariable finding
- Pelizaeus-Merzbacher Disease (PLP1 Mutation)
2. Cockayne Syndrome
This leukodystrophy can be treated by transplant of HLA-matched umbilical cord hematopoietic cells in asymptomatic babies + substantial antirejection medication
Globoid Cell Leukodystrophy (Krabbe Disease, Galactocerebrosidase Deficiency, GALC Mutation)
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)
Spongy degeneration of Infancy (Canavan-van Bogaert-Bertrand or Canavan disease)
Autosomal recessive disease characterized by stippled, irregular calcifications of the patellae and greater trochanters
Cerebrohepatorenal Zellweger Disease
Classic triad of trismus, strabismus and opisthotonus
Gaucher disease
Macrocephaly (enlarging head without hydrocephalus) is seen the ff infantile inherited metabolic disorders
Canavan spongy degeneration of infancy
Tay-Sachs disease (some)
Alexander disease
Infantile inherited metabolic disorder characterized by colorless, friable hair, that appear twisted under the microscope (pili torti)
Menkes Disease (aka Trichopoliodystrophy or ATP7A Mutation)
Treatment for Menkes disease
Copper histidine SC BID
Must be started in the first weeks of life to permit normal neurodevelopment
Infantile inherited metabolic disease that presents with opthalmic signs of bilateral cataracts, glaucoma, large eyes, megalocornea, bupthalmos, and blindness.
Oculocerebrorenal (Lowe) syndrome
OCRL1 mutation
Autosomal disorder presenting in infancy with hoarse cry and characteristic periarticular and subcutaneous swellings and progressive arthropathy leading to ankylosis
Farber Disease (Lipogranulomatosis) ASAH1 Mutation Or Ceramidase deficiency
Rosenthal fibers
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
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
Infantile Generalized GM1 Gangliosidosis
Mucopolysaccharidosis
Infantile inherited metabolic disorders associated with cataracts
Galactosemia
Lowe disease
Zellweger disease
The inherited Hyperammonemias are of the autosomal recessive pattern EXCEPT
Ornithine transcarbamylase deficiency - X-linked dominant
This inherited Hyperammonemia presents with excessive dryness and brittleness of the hair (trichorrhexis nodosa)
Argininosuccinic aciduria
Enzyme lacking in Maple Syrup Urine Disease?
What accumulates as a result?
Deficiency in alpha-keto acid dehydrogenase resulting in the accumulation of branched chain amino acids: leucine, isoleucine, valine
Garrod’s cardinal principle of gene action
Genetic factors specify chemical reactions as well as biochemical individuality
Level of serum phenylalanine which with phenylpyruvic acid in the urine, blood and CSF, is diagnostic of PKU
Above 15mg/dL
Autosomal recessive amino acid disorder characterized by intermittent red scaly rash, episodic personality disorder and episodic cerebellar ataxia
Hartnup disease (SLC6A19 mutation)
What is the only treatment shown to stabilize and reverse some of the MRI changes of Adrenoleukodystrophy?
Bone marrow transplantation
Identified locus of the following mitochondrial disorders Leigh Disease NARP MERRF MELAS
Leigh Disease locus 8993
NARP locus 8993
MERRF locus 8344
MELAS locus 3243
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.
Gomori trichome stain
The pathologic findings of Leigh disease resemble but are more extensive than that of Wernicke disease and spares this structure
Mammillary bodies
The mutation resulting in the syndrome of Sensory NARP creates a defect in which mitochondrial/respiratory chain protein?
ATPase-6 of complex V