Fatal hyperammonemia in the setting of late-onset argininosuccinic acid lyase enzyme deficiency (ASLD): a case report

Background: The urea cycle is composed of multiple catalytic steps that are required for the metabolism of waste products and the recycling of various amino acids. These catalytic steps are composed of a harmonious array of various essential enzymes and corresponding intermediate products. Enzymatic deficiency in any of these steps can lead to the accumulation of precursor metabolites and waste ammonia, resulting in biochemical derangements and a clinical picture of neurologic deterioration and critical multiorgan compromise. Argininosuccinic acid lyase deficiency (ASLD) is one of the subtypes of urea cycle disease. Case Description: A 51-year-old male with sepsis and acute renal failure secondary to obstructive uropathy was found with a sudden elevation of ammonia to 509 µmol/L and development of diffuse cerebral edema. Urea cycle disease was suspected and confirmed with a metabolic panel consistent with ASLD. A reduction of ammonia was achieved via dialysis therapy. However, the patient developed a second decompensating event with worsened hyperammonemia requiring pressor support. The patient was made palliative by family and expired shortly after withdrawal of pressor support. Conclusions: Late-onset ASLD presentation has been associated with manifestation of disease following the presence of a stressor or event. Hyperammonemia is a hallmark feature of the disease, resulting from impaired detoxification of ammonia due to ASLD. But other factors such as infection and nutrition can further biochemically exacerbate the disease. The development of neurological complications, such as cerebral edema, stands out as a prominent concern. And furthermore, a delay in confirmatory testing can limit therapeutic and prognostic measures.