Long‐Term Follow‐Up of Patients With Mitochondrial Carbonic Anhydrase VA Deficiency. A Case Report and Literature Review

ABSTRACT

Mitochondrial carbonic anhydrase VA (CA‐VA) deficiency is a rare inherited metabolic disorder caused by biallelic variants of the CA5A gene. It presents with hyperammonemia, lactic acidosis, and ketonuria, with or without hypoglycemia. We report the long‐term follow‐up of the first two reported cases of CA‐VA deficiency: a 16‐year‐old female (case 1) and her 14‐year‐old brother (case 2), both of whom presented with neonatal hyperammonemic encephalopathy, hypoglycemia, elevated lactate, ketonuria, and compensated metabolic acidosis. The diagnosis was made in both cases through the TIDEX study, which identified a homozygous pathogenic variant in the CA5A gene (c.697T>C, (p.Ser233Pro)). The clinical course of the index patient revealed three additional metabolic decompensation episodes (MDEs) triggered by intercurrent illnesses, with the last episode occurring at 8 years of age, highlighting the unusual timing of her MDEs compared to previously reported cases. Case 2 remained metabolically stable without any additional MDEs. These episodes were successfully treated with parenteral dextrose, a single dose of enteral carglumic acid, and occasionally parenteral lipids. Management of intercurrent illness included a sick‐day formula high in carbohydrates and fats. Currently, both cases show normal growth, development, and neurological outcomes, suggesting a favorable prognosis, and in keeping with previously reported cases. Early diagnosis of CA‐VA deficiency allows prompt treatment and prevents severe complications. With proper management, long‐term outcomes are favorable, although severe and fatal outcomes have been reported. The impact on longevity needs to be assessed over longer durations. The development of consensus management for CA‐VA deficiency is warranted.