Urea Cycle Disorders Flashcards
OTC Deficiency (genetics/severity) Ornithine Transcarbamylase
X-LINKED
Most common urea cycle disorder
Severe (males without enzyme often die as newborns)
15% of female carriers have clinical symptoms
OTC defic Labs/diagnx
Serum aa: low citrulline, high glutamine
Urine: elevated orotic acid (organic)
CPS1 defic (severity)
Carbomylphosphate Synthatase 1
SEVERE
Genetics of Urea Cycle defic
All are AR
except OTC that is X-linked
Plasma NH3 in Urea Cycle Defic
> 150 umol/L WITH A NORMAL ANION GAP AND NORMAL GLUCOSE
and mutations on molecular analysis
Citrullemia Type 1/ASS1 Defic
Argininosuccinate SYNTHETASE 1
SEVERE but still able to incorporate SOME nitrogen into urea cycle intermediates
HIGH CITRULLINE
Argininosuccinic Aciduria/ASL Defic
other sx
Argininosuccinate LYASE
Chronic hepatomegaly, trichorrhexis nodosa (node like appearance of fragile hair)
High citrulline
Enlarged hepatocytes (my progress to fibrosis)
Poss AST/ALT elevations
NAGS defic
N-acetyl glutamate synthetase
Resmbles CPS1 defic as defic is in enzyme that yeidls CPS1 cofactor
ARG defic, ORT-1 defic, Citrin defic PRES
Milder
Hyperammonemia sx triggered by stress/ilness
Can develop:
progressive spasticity, tremor, ataxia, choreoathetosis
Pres for all but the milders
Depends on enzyme, partial defic can present like milders
Normal at birth but can develop hyperammonemia within first few days of life
Cerebral edema, lethargy, early HYPERventilation
Hypothermia, seizurues, vomiting, psychoses, HYPOventilation as cerebral edema progresses
Acute Hyperammonemia Treatment
Dialysis and hemofiltration
Ammonia scavenging drugs (Na benzoate, Na phenylacetate)
Limit dietary protein
IV fluids and cardiac pressors (but avoid overhydration)
Arginine/citrulline as appropriate
Chronic Hyperammonemia Treatment
Limit dietary protein
Supplement certain aa
LIVER TRANSPLANT for server neonatal pres or recurrent episodes after max medical tx
Genetic counseling
