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Case Reports
. 2020 Oct 1;57(1):9-14.
doi: 10.1002/jmd2.12171. eCollection 2021 Jan.

Two cases of carbonic anhydrase VA deficiency-An ultrarare metabolic decompensation syndrome presenting with hyperammonemia, lactic acidosis, ketonuria, and good clinical outcome

Ashish Marwaha  1 , Judy Ibrahim  2 , Taylor Rice  3 , Nadia Hamwi  2 , Charles Anthony Rupar  4   5   6 , David Cresswell  7 , Chitra Prasad  6 , Andreas Schulze  1   8   9
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Case Reports

Two cases of carbonic anhydrase VA deficiency-An ultrarare metabolic decompensation syndrome presenting with hyperammonemia, lactic acidosis, ketonuria, and good clinical outcome

Ashish Marwaha et al. JIMD Rep. .

Abstract

The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency. We present two cases of this rare inborn error of metabolism. Both newborns with South Asian ancestry presented with a metabolic decompensation characterized by hyperammonemia, lactic acidosis and ketonuria; one also had hypoglycemia. Standard metabolic investigations (plasma amino acids, acylcarnitine profile, and urine organic acids) were not indicative of a specific organic aciduria or fatty acid oxidation defect but had some overlapping features with a urea cycle disorder (elevated glutamine, orotic acid, and low arginine). Hyperammonemia was treated initially with nitrogen scavenger therapy and carglumic acid. One patient required hemodialysis. Both have had a favorable long-term prognosis after their initial metabolic decompensation. Genetic testing confirmed the diagnosis of carbonic anhydrase VA (CA-VA) deficiency due to biallelic pathogenic variants in CA5A. These cases are in line with 15 cases previously described in the literature, making the phenotypic presentation pathognomonic for this ultrarare (potentially underdiagnosed) inborn error of metabolism with a good prognosis.

Keywords: encephalopathy; ketonuria; lactic acidosis; metabolic acidosis; neonatal hyperammonemia.

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Conflict of interest statement

All authors have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
The intermediary metabolism of carbonic anhydrase (CA‐VA). Carbonic anhydrases catalyze the reversible hydration of carbon dioxide and produce bicarbonate. Human carbonic anhydrase VA (CA‐VA) is a mitochondrial enzyme present in the liver, kidney, and skeletal muscle. CA‐VA supplies bicarbonate as a substrate of four mitochondrial enzymes: carbamoyl phosphate synthetase 1 (CPS1), 3‐methylcrotonyl‐CoA carboxylase (3MCC), propionyl‐CoA carboxylase (PCC), and pyruvate carboxylase (PC)
See this image and copyright information in PMC

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