Urea Cycle Defects Flashcards
Primary cause of hyperammonemia
urea cycle disorders
Secondary causes of hyperammonemia
organic acidemias, fatty acid oxidation disorders, carnitine cycle disorders, transient hyperammonemia of the newborn (THAN), liver failure, asparaginase treatment, valproate therapy
Symptoms of acute hyperammonemia
altered consciousness (similar to drug intoxication), acute encephalopathy, seizures, psych sx
Symptoms of chronic hyperammonemia
neuropsych sx, migraines, tremor, ataxia, dysarthria, learning disabilities, failure to thrive, hepatomegaly (elevated liver enzymes)
Triggers of hyperammonemic crises in urea cycle disorder patients
infections, fever, vomiting, GI bleed, decreased PO intake, chemotherapy, high-dose glucocorticoids
Ornithine transcarbamylase (OTC) deficiency
most common urea cycle disorder. X-linked
male hemizygotes may not survive newborn period
female heterozygotes –> mild-severe sx
OTC presentation
4 day old male with lethargy, poor feeding, emesis; acute AMS. Hypertonic, hyperreflexic, possible seizures
VBG –> respiratory alkalosis
hyperammonemia
FH: mat uncle died at 6 days of life c progressive lethargy and coma
Plasma amino acids: low citrulline, elevated glutamine
Urine organic acids: elevated orotic acid
Diagnostic test for OTC deficiency
hemizygote for p.T178M mutation
Ammonia scavenging agents
Sodium Phenylacetate (uses glutamine) and Sodium Benzoate (uses glycine)
UCD treatment strategies
protein restriction, ammonia scavenging medications, L-arginine or L-citrulline supplementation, hemodialysis for acute severe hyperammonemia
liver transplant for recurrent hyperammonemia or brittle disease that is refractory to medical management
UCDs not routinely detected on NBS
N-acetylglutamate deficiency, CPS1 deficiency, OTC deficiency
all occur in the mitochondria
