Arginase Deficiency Clinical Presentation

Updated: Jan 07, 2019
  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
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Presentation

History

A history of delayed development, protein intolerance, and spasticity is suggestive of arginase deficiency. [8]

Although a catastrophic neonatal presentation is uncommon in patients with arginase deficiency, surmising that onset is at birth and that progression is relatively slow compared with other urea cycle disorders is reasonable. Specifically, dietary protein intolerance is an early sign and should not be overlooked.

The typical presentation is that of an older infant whose development is delayed, who has occasional episodes of vomiting and somnolence without apparent cause, who is protein intolerant, and who shows evidence of long-tract neurological impairment.

A common clinical feature in this disorder is spasticity, and the disease is likely underdiagnosed because many affected children are diagnosed with cerebral palsy without effort to diagnose arginase deficiency.

The multiple primary causes of hyperammonemia, specifically those due to urea cycle enzyme deficiencies, vary in presentation, diagnostic features, and treatment. For these reasons, disorders in the urea cycle defect family are individually considered in this article; however, hyperammonemia is a common denominator and can present with some or all of the following symptoms:

  • Anorexia

  • Irritability

  • Heavy or rapid breathing

  • Lethargy

  • Vomiting

  • Disorientation

  • Somnolence

  • Asterixis (rare)

  • Combativeness

  • Obtundation

  • Coma

  • Cerebral edema

  • Death (if treatment is not forthcoming or effective)

As a consequence, the most striking clinical findings of each individual urea cycle disorder relate to the constellation of symptoms of hyperammonemia and rough temporal sequence of events.

Arginase deficiency may have a somewhat different manifestation for reasons cited above.

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Physical

General

Signs of severe hyperammonemia may be present.

Poor growth may be observed.

Head, ears, eyes, nose, and throat (HEENT)

Papilledema may be present if cerebral edema and increased intracranial pressure have ensued.

Pulmonary

See the list below:

  • Tachypnea or hyperpnea may be present.

  • Apnea and respiratory failure may occur in latter stages.

Abdominal

Hepatomegaly may be present and is usually mild.

Neurologic

See the list below:

  • Poor coordination and spasticity

  • Hyperreflexia

  • Dysdiadochokinesia

  • Hypotonia or hypertonia

  • Ataxia

  • Tremor

  • Seizures and hypothermia

  • Lethargy progressing to combativeness to obtundation to coma; decorticate or decerebrate posturing if profound hyperammonemia present

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Causes

The gene for liver arginase has been cloned and is located on chromosome 6. It has been mapped to locus 6q23, consists of 11.5 kilobases, and comprises 8 exons. A mouse "knockout" model for arginase I deficiency has been produced. These animals die within 10-12 days of birth of severe hyperammonemia, whereas animals deficient in arginase II have no identifiable phenotype, except for impaired fertility in the male.

Approximately 40 mutational variants have been identified. [9]

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