Genetic Disorders of Metabolic Pathways Flashcards
A patient presents with: severe intellectual disability, microcephaly, light hair, bluish eyes, convulsion movements, characteristic body order as musty or mousy. what is the diagnosis?
Phenylketonuria. (blue eyes light hair is cuz it interferes with production of melanin
In classical PKU, what enzyme is absent?
pheynlalanine hydoryxlase which converts Phe into tyrosine. THe conversion is halted
what is the cause of secondary PKU
Insufficient BH4 leading to BH2 deficiency.
What are some major clinical findings with secondary PKU?
abnormal response to diet , progressive detoerioation. May respond to BH4 treatment.
Due to lack of BH4 what enzyme is not able to function as seen in secondary pku?
dihydropterine reductase
what gives the mousy sell as seen in Pku?
build up of phenylacetate
build up of what side product leads to problem with shutting of glucose to the brain?
phenylpyruvate
what can be detected in urine in PKU?
phenylketones
what are some consequences of excess phenylalanine and its metabolites as seen in PKU?
- toxic to infant neurological tissues: inhibits: tyrosinase - decrease in pigmentation, seraotnin decarboxylase - decrease in serotonin synthesis; glutamate decarboxylase - decrease in GBA synthesis and posisble decrease in all catecholamines.
- loss of IQ
what is the normal blood level of Phe and what is in in PKU?
normal 1mg
PKU: 10-60 mx/dL (target is to get to 3-15 in tx)
what are two lab tests used to check Phe in diagnosing PKU?
Guthrie test - bacterial inhibition essay
Mass tendem spectorphtometry
In alkapturia, what aminoa acid is defective?
tyrosine
in alkapturia, what enzyme is defective and what is the build up product?
hoogentisate oxidase is defective so homogentisate builds up as it cannot go to maleylacetoacetate.
around what are does alkpatouria usually present and what are some physical finding?
around 20-30s with discoloration of sclera (ochronosis), dark-colored urine (or, darkens on standing)
As a result of build up of homogentisate as seen in alkaptouria, what clinical signs are seen?
severe degeneraiton of cartilage of the spine and other major joints (osteoarthris),
kidney disease
In albinism what enzyme is defective and what is the build up productive?
tyrosinase is defective and so tyrosine builds up. Tyrosine metabolism is needed cuz it produces melanin which is needed for skin color.
if an infant presnts with cabbage-like odor of urine and liver failure, what is the likely diagnosis?
Tyrosinemia
In type I tyrosinemia, what enzyme is defective and what is the build up product?
fumarylacetoacetate hydrolase. build up product is fumarylacetoacetate. Cannot make acetoacetate fumerate
In type I tyrosinemia, what is the toxic agent that causes the clinical signs?
Becuase fumerylacetoacetate builds up, it follows an alternate pathway and produces succinylacetone (succinylCoa as needed in TCA and heme synthessi)
In classical homocystinuria, what enzyme is defective?
cystahionine beta-synthease which requires pyridoxine (B6)
True or false: homocysteine is a normal metabolite?
True. It can build up in abnormal condition and spontaneous go to homocystine.
homocysteine is needed for what physioogical compound?
glutathione
Homocysteine can go back to methionine if what cofactors are present?
B6, B12 and folic acid
In classica homocystinuria, what compound is produced as a result of homocysteine build up?
homocysteine thiolactone which reacts readily with proteins of cysine residues
