Congenital Metobolic Diseases Flashcards
What is the most common aminoacidopathy?
phenyketonuria
What is the inheritance of phenylketonuria?
AR
What are hallmark exam findings in PKU? How is it treated?
fair skinned blue eyed kid with musty odor
limit phenylalanine consumption
The aminoacidopathies are generally inherited in _____ fashion.
AR
What is the inheritance of homocystinuria?
AR
What is the deficient enzyme in PKU?
phenylalanine hydroxylase
What is the deficient enzyme in homocystinuria?
cystathionine B-synthase
What is the symptomatology of homocystinuiria?
similar to Marfan’s syndrome, but with mental retardation and increased incidence of stroke, lens dislocations, and arachnodactyly
What is a key finding in maple syrup urine disease?
burned sugar smell in the urine
What’s the inheritance of maple syrup urine disease?
AR
What is the deficient enzyme in maple syrup urine disease?
branched chain a-keto acid dehydrogenase
What is Hartnup disease?
aminoacidopathy, cannot absorb neutral amino acids
develop Niacin deficiency with pellegra like symptoms
The sphingolipidoses are inherited in ______ fashion except for ____, which is _____.
AR
Fabry, XR
What enzyme is deficient and what accumulates:
Nieman Pick
Sphingomyelinase
Sphingomyelin
What enzyme is deficient and what accumulates:
Gaucher
Glucocerebrosidase
Glucocerebreside
What enzyme is deficient and what accumulates:
Fabry
a-galactosidase
ceramides
What enzyme is deficient and what accumulates:
Tay Sachs
Hexosaminadase A
GM2 gangliosides
What enzyme is deficient and what accumulates:
Sandhoff
Hexosaminidase A and B
GM2 gangliosides
What enzyme is deficient and what accumulates:
GM1 gangliosidosis
B-galactosidase
GM1 gangliosides
Which sphingolipidoses cause cherry red spots?
Niemann Pick
Tay Sachs
GM1 Gangliosidosis
Gaucher
Which sphingolipidoses affect Ashkenazi Jews?
Niemann Pick
Tay Sachs
What are key findings in Niemann Pick?
cherry red spot, vertical gaze palsy, MR, hepatosplenomegaly
What are Niemann Pick cells?
foamy cells; large vacuolated histiocytes and lymphocytes
What is the most frequent sphingolipidosis?
Gaucher
What are Gaucher cells?
wrinkled tissue paper appearing cells
What are key findings in Gaucher disease?
hypersplenism with anemia and thrombocytopenia
What are key findings in Fabry disease?
painful dysesthesias, vascular disease (Htn, renal, death by MI or stroke in adulthood)
What are key findings in Tay Sachs disease?
MACROcephaly, cherry red spot (NO organomegaly)
What are clinical findings in Sandhoff disease?
similar to tay sachs but has visceral storage
What are key findings in GM1 gangliosidase?
dysmorphic face, cherry red spot, hepatosplenomegaly, bone abnormalities
Mucopolysaccharidoses are all _______ inheritance except _____ which is _____.
AR
Hunter, XR
What is the enzyme deficiency and urine sulfate metabolite for the following:
Hurler
a-L-iduronidase
Heparan and dermatan
What is the enzyme deficiency and urine sulfate metabolite for the following:
Scheie
a-L-iduronidase
Heparan and dermatan
What is the enzyme deficiency and urine sulfate metabolite for the following:
Hunter
iduronidase sulfatase
Heparan and dermatan
What is the enzyme deficiency and urine sulfate metabolite for the following:
San filippo
Sulfamidase
Heparan
What is the enzyme deficiency and urine sulfate metabolite for the following:
Morquio
B galactosidase
Keratin
What is the enzyme deficiency and urine sulfate metabolite for the following:
Maroteaux Lamy
Sulfatase B
Dermatan
What is the enzyme deficiency and urine sulfate metabolite for the following:
Sly
B-glucoronidase
Heparan and Dermatan
What are key features of Hurler’s disease?
gargoyle face, MR, dwarfism, corneal clouding, skeletal abnormalities, thick meninges (can cause spinal cord compression)
What are Zebra bodies?
seen on electron microscopy with Hurler’s disease
What are key features of Scheie?
milder Hurler, no MR
What are key features of Hunter?
milder Hurlery, no MR and less corneal clouding; classic skin pebbling and peripheral nerve entrapment (Carpel tunnel)
Which MPS has the most severe skeletal deformities and ligamentous laxity?
Morquio
Which MPS can have carpel tunnel syndrome?
Hunter, Scheie, Maroteaux Lamy
Which MPS classically has hydrocephalus?
Sly
The leukodystrophies are all _____ inheritance except for _____ which are ____ and _____ which is ____.
AR
Adrenoleukodystrophy and Pelizaeus-Merzbacher, XR
Alexander, sporadic
Which leukodystrophy is associated with Ashkenazi Jews?
Canavan
What is the enzyme deficiency and what accumulates:
Krabbe
galactocerebroside β-galactosidase
galactocerebroside
What is the enzyme deficiency and what accumulates:
Metachromatic leukodystrophy
arylsulfatase A
sulfatides
What is the enzyme deficiency and what accumulates:
Adrenoleukodystrophy?
ABCD 1
long chain fatty acids
Leukodystrophies have cavitation or degeneration of ______ but spare _____ except for ______ which preferentially targets them.
white matter
subcortical U fibers
Canavan
Which leukodystrophy is associated with adrenal insufficiency and bronze skin?
adrenoleukodystrophy
What CT finding is unique to Krabbe disease?
hyperdense basal ganglia and thalamus
What is seen on histology for Krabbe disease?
Globoid cells; large macrophages around blood vessels
What is the treatment in adrenoleukodystrophy?
Lorenzo oil and diet low in long chain fatty acids
Which leukodystrophy has a Tigeroid pattern on MRI?
Pelizaeus Merzbacher
Alzheimer type II astrocytes are seen in what leukodystrophy?
Canavan
What are the key clinical features of MELAS?
encephalopathy, lacitc acidosis, stroke like episodes with cortical blindnesss
What are the key clinical features with MERRF?
myoclonic epilepsy with ragged red fibers on muscle biopsy
How is Kearns Sayre syndrome inherited?
mitochondrial
Which mitochondrial diseases have ragged red fibers on muscle biopsy?
MERRF and Kearns Sayre
What are key clinical findings in Kearns Sayre?
cardiomyopathy and ophthalmoplegia/retinal issues
What is the inheritance of Lebers hereditary optic neuropathy?
mitochondrial
What are the key clinical findings in levers hereditary optic neuropathy?
progressive painless loss of central visiosn
What is the inheritance of Menke Kinky hair disease?
XR
Menke kinky hair disease is due to a defect in ____ causing decrease in _____.
Copper transporting ATPase
GI absorption of copper
What are the key clinical features of Menke Kinky hair disease?
tortuous vessels, metaphysial spurring, brittle colorless hair growth, seizures, MR
What is the inheritance of Leigh disease?
AR
What is the deficient enzyme in leigh disease?
cytochrome C oxidase
Leigh disease results in ______ leading to diffuse neurologic deficits such as _____.
bilateral symmetric spongiform degeneration and necrosis of the thalamus, basal ganglia, brainstem, and spinal cord with peripheral nerve demyelination
decreased muscle tone and head control, seizures, myoclonus, ophthalmoplegia, and respiratory and swallowing problems
What’s another name for Lowe syndrome? How is it inherited?
XR
oculocerebrorenal syndrome (cataracts, MR, death by renal failure)
What is the inheritance of Lesch-nyhan syndrome? What is the deficient enzyme? What are its key clinical features?
XR
HGPRT
accumulation of uric acid leading to choreoathetosis and self mutilation
What is Zellweger syndrome? What’s another name for it?
XR
Cererbrohepatorenal syndrome (cortical dysgensis, hepatorenal failure)
