36 Inherited Metabolic Diseases Flashcards
pattern of inheritance which has a characteristic of variable degree of penetrance and expressivity
autosomal dominant pattern
agenesis of the cerebellum,
early cerebellar ataxia (with or without mental retardation) and episodic hyperventilation, selective agenesis of the vermis
Joubert Syndrome
familial cerebellar ataxia with RETINAL DEGENERATION
Behr disease
Match the deficient enzyme with the disease
- Krabbe’s Disease
- Homocystinuria
- Pompe’s Disease
- Metachromatic Leukodystrophy
a. cystathionine beta synthesise
b. arylsulfatase A
c. Alpha glucosidase
d. Galactocerebroside beta galactosidase
- Krabbe’s Disease - Galactocerebroside beta galactosidase
- Homocystinuria - Cystathionine beta synthesase
- Pompe’s Disease - alpha glucosidase
- Metachromatic Leukodystrophy - arylsulfatase A
Match the pathologic finding:
- alexander’s disease
- niemann-pick disease
- neuronal ceroid lipofuscinosis
- Zellweger syndrome
a. sea-blue histiocytes
b. fingerprint inclusions
c. peroxisome ghosts
d. rosenthal fibers
- alexander’s disease - rosenthal fibers
- niemann-pick disease -
- neuronal ceroid lipofuscinosis
- Zellweger syndrome
Early onset convulsions
Jittery baby
irritability
exaggerated auditory startle response and psychomotor retardation
- what is the gene mutation?
- treatment?
case of pyridoxine dependent seizures
- ALDH7A1 mutation
- vitamin B6 (pyridoxine) 50-100 mg
onset of symptoms start first days of life after ingestion of milk
presents with diarrhea, vomiting, failure to thrive, hypotonia
(+) Cataracts
- What is the disease?
- Gene mutation
- Treatment
- Galactosemia
- GALT mutation
- milk substitutes
presents with recurrent forms of episodic cerebellar ataxia
+ striking odor/ stale perspiration
“sweaty foot syndrome”
isovaleric acidemia
- enzyme deficient in maple syrup urine disease
2. what accumulates?
- a-ketoacid dehydrogenase
2. accumulation of branched chain amino acids: leucine, isoleucine and valine
onset before 6 months presenting as generalized rigidity, loss of head control
opisthotonic recurvation of the neck and trunk, optic atrophy
with loss of tendon reflexes but with babinski signs
on imaging: symmetrical non enhancing areas of increased signal in the Internal capsule and basal ganglia
Krabbe disease
aka
globoid cell leukodystrophy
mutation: GALC mutation
onset at first months of life presenting with abnormal eye movements (rapid, irregular and often asymmetrical pendular nystagmus)
+ spastic weakness of limbs, optic atrophy
+ titubation of head
cerebellar signs
Patho: TIGROID pattern of degeneration and intact myelin in cerebellum
- What is the disease?
- Type of Inheritance?
- Pelizaeus-Merzbacher Disease
2. X-linked
presents as failure to thrive, psychomotor retardation, spasticity of craniospinal musculature, seizures
Pathologically: with severe destructive changes of the white matter, most intense in the frontal lobe
+ eosinophilic bodies (ROSENTHAL FIBERS)
- What disease?
- Gene mutation?
- Alexander Disease
2. GFAP
This disease presents with progressive cerebral poliodystrophy or diffuse cerebral degeneration in infancy
progressive disease of the cerebral GRAY matter
“Walnut brain” - Marked atrophy of the cerebral convolutions and cerebral cortex with loss of nerve cells and fibrous gliosis.
Alpers
