Argininosuccinate Lyase (ASL) Deficiency Clinical Presentation

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

History

The neonatal presentation of argininosuccinate (ASA) lyase deficiency is consistent with the clinical manifestations of hyperammonemia. The multiple primary causes of hyperammonemia, specifically the urea cycle enzyme deficiencies, vary in manifestation, diagnostic features, and management. For these reasons, the urea cycle defects are considered individually in this article; however, hyperammonemia is the common denominator and can manifest clinically as 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)

The most striking clinical findings of each individual urea cycle disorder consequently relate to the foregoing constellation of symptoms and their temporal sequence.

Delayed development and mental retardation are among the long-term consequences in survivors who do not receive proper treatment.

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Physical

See the list below:

  • General

    • Signs of severe hyperammonemia may be present.

    • Poor growth may be evident.

  • Head, ears, eyes, nose, and throat: Papilledema may be present if cerebral edema and increased intracranial pressure have occurred.

  • Pulmonary

    • Tachypnea or hyperpnea may be present.

    • Apnea and respiratory failure may occur in later stages.

  • Abdominal: Hepatomegaly is common.

  • Neurologic

    • Poor coordination

    • Dysdiadochokinesia

    • Hypotonia or hypertonia

    • Ataxia

    • Tremor

    • Seizures and hypothermia

    • Lethargy progressing to combativeness, obtundation, and coma

    • Decorticate or decerebrate posturing

  • Other: A distinguishing feature in the newborn period, unique to urea cycle defects, is the presence of trichorrhexis nodosa (friable hair). This may be observed clinically and is identifiable with microscopic examination. Trichorrhexis nodosa is likely to be much more apparent in older infants, who may also have a choreoathetotic movement disorder.

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Causes

ASA lyase deficiency is an autosomal recessive genetic disorder. The gene for ASA lyase deficiency is located on chromosome 7 and has been mapped to the locus 7q11.2. The normal gene has been cloned and comprises approximately 35 kilobases and 16 exons. Approximately 160 mutational variants have been reported, most of which are private and vary widely in nature, from missense to deletions.

Urea cycle defects with resulting hyperammonemia are due to deficiencies of the enzymes involved in waste nitrogen metabolism. These enzyme deficiencies lead to disorders with nearly identical clinical presentations. The exception is arginase, the last enzyme of the cycle; arginase deficiency causes a somewhat different set of signs and symptoms (see Arginase Deficiency).

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Complications

In a follow-up study of patients with ASA lyase deficiency, hepatic fibrosis was reported in some cases [9] ; however, other studies have not confirmed this as a regular long-term complication, [10] while EEG changes progress independently of hyperammonemic control.

Untreated patients may develop cerebral edema and die, and some patients die despite treatment.

Mental retardation is a common sequela.

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