PEDBASE.org - The Pediatric Database -
Detailed information of ARGININEMIA
ARGININEMIA
DEFINITION:
A disorder of the urea cycle characterized by the accumulation of
ammonia resulting in an altered level of consciousness and other
neurological manifestations.
EPIDEMIOLOGY:
- incidence: rare (about 25 cases reported)
- age of onset:
- risk factors:
- familial - autosomal recessive
- chrom.#: 6q23
- gene: arginase
- M = F
PATHOGENESIS:
- arginase is the fifth and final enzyme in the urea cycle
- a cytosolic enzyme, arginase catalyzes the conversion of
arginine to ornithine + urea
2. Genetic Defect
- genetic defect -> deficiency of arginase -> accumulation of
ammonia and arginine
- ammonia is a neurotoxin affecting the CNS
- arginine accumulates in the blood, CSF, and urine
- recurrent episodes of severe hyperammonemia are usually not
present in this disorder
CLINICAL FEATURES:
- asymptomatic for the first few months to years of life
- insidious onset with presentation in childhood (2-3 years):
- increased clumsiness
- spastic quadriplegia (lower > upper limbs) with loss of
ambulation eventually
2. Speech and Language
3. Cognition
- progressive mental retardation
2. Others
- choreoathetotic movements
- seizures + EEG anomalies
- hepatomegaly
INVESTIGATIONS:
- venous hyperammonemia
- normal anion gap; respiratory alkalosis
- amino acids
- citrulline between 100-300 uM)
- elevated arginine (>1 uM)
- other amino acids are normal
2. Urine
- elevated arginine, lysine, cystine, ornithine, and orotic
acid
3. Diagnosis
- deficiency of arginase activity in liver samples and RBC
lysates (can be obtained from cord samples)
MANAGEMENT:
- a chronic progressive disorder and thus must:
- provide long-term follow-up
- moniter ammonia levels
- coordinate a multidisciplinary approach:
- Paediatrics, Neurology, Dietary, Genetics, Metabolics
2. Goals of Therapy
- asymptomatic control of and avoidance of acute episodes
- not curative
3. Diet
- Mead Johnson 80056 Formula
- non-protein containing formula
- supplement with arginine
2. Endogenous
- High Caloric Diet
- use to minimize tissue catabolism and thus the
breakdown of endogenous protein
4. Convert Nitrogen to an Excretable Compound
- conjugate with glycine and excreted as hippuric acid
2. Sodium Phenylacetate
- conjugate with glutamine and excreted as phenylacetyl-glutamine
3. Dialysis
- Peritoneal or Hemodialysis
5. Prognosis
- good prognosis if disorder is treated prospectively from
birth
- progressive neurological manifestations if untreated
|
Pediatric Database - ARGININEMIA
Pediatric Organization - Pedbase [at] Gmail.com