Urea Cycle Disorder Flashcards
2 major functions of urea cycle
- Removal of nitrogenous waste
2. Synthesis of amino acids
Primary location of urea cycle
Hepatocytes
Consequences of acute elevation of ammonia
Seizures, coma, death
Consequences of mild chronic elevations of ammonia
Brain atrophy, cognitive impairment
Non genetics causes of hyperammonemia
Infections
Toxins
Trauma
Ischemia
OTC inheritance and gene
XLR, OTC
OTC enzyme deficiency
Ornithine transcarbamylase deficiency
Plasma AA in OTC
Elevated: orotic acid and ammonia
Low: citrullinr, ASS, ARG
ASS1 deficiency inheritance and gene
AR, ASS1
ASS1 enzyme deficiency
Argininosuccinic acid synthase I deficiency
Plasma AA profile for ASS1
Elevated: citrulline, glutamine, alanine, orotic acid
Low: ASA, Arg, ornithind
ASL deficiency inheritance and gene
AR, ASL
ASL enzyme deficiency
Argininosuccinate lyase deficiency
Plasma AA profile for ASL
Elevated: ASA, citrulline, glutamine, ala
Low: arg, ornithind
ARG deficiency inheritance and gene
AR, ARG1
ARG enzyme deficiency
Arginase deficiency
Plasma AA for ARG deficiency
Elevated: arginine
NAGS and CPS1 deficiency inheritance and gene
AR, NAGS/CPS1
NAGS and CPS1 enzyme deficiency
N-acetylglutsmate synthase
Carbomohl phosphate synthetase deficiency
Plasma AA profile in NAGS/CPS1 deficiency
Elevated: glutamine, alanine
Low: citrulline, AAS, Arg, orotic acid
Untreated OTC 2-3 days old
Progressive hyperammonemia encephalopathy
Untreated OTC 1 week old
Lethal hyperammonemic encephalopathy
Prenatal dx of OTC deficiency
Molecular testing of familial mutation
Untreated ASS1 4-7 days old
Progressive hyperammonemia encephalopathy
Untreated ASS1 1-2 weeks old
Lethal hyperammonemic encephalopathy
Prenatal dx of ASS1
Molecular testing of familial mutation
ASS1 enzyme activity measured on CVS/amnio
Untreated ASL deficiency 4-7 days old
Progressive hyperammonemic encephalopathy
Untreated ASL deficiency 1-2 weeks old
Lethal hyperamonemic encephalopathy
Progressive hyperammonemic encephalopathy
Poor feeding Vomiting Lethargy Hyperventilation Seizures
Lethal hyperammonemic encephalopathy
Cerebral adema Hypothermia Coma Respiratory failure Death
Prenatal dx of ASL deficiency
Molecular testing of familial mutation
ASL enzyme activity of CVS or amnio
Elevated arginosuccinic acid levels in amniotic fluid suggestive of ASL deficiency
ARG deficiency after 1-3 years
Growth slows
Motor and cognitive development slows + regression
Spasticity and seizures develop
Untreated ARG deficiency in adulthood
Severe MR, microcephaly
Short stature
Severe spasticity and joint contractures
Lack of ambulation, bowel and bladder control
Prenatal dx for ARG deficiency
Molecular testing of familial mutation
ARG enzyme activity on RBCs (PUBs)
Untreated NAGS and CPS1 deficiency
Neonatal hyperammonemia encephalopathy
Prenatal dx of NAGS and CPS1
Molecular testing if familial mutation known
