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CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1249480
Two siblings with very late onset of holocarboxylase synthase deficiency and a mini-review
Provisionally accepted- 1 Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- 2 INSERM U1211 Maladies rares, Génétique et métabolisme (MRGM), Bordeaux, Aquitaine, France
Holocarboxylase synthase (HCS) deficiency is an extremely rare metabolic disorder typically presenting as severe neonatal metabolic acidosis, lethargy, hypotonia, vomiting, and seizures. This report describes two siblings in a family with late-onset forms of HCS deficiency. The younger sister presented at the age of 11 years and manifested as acute metabolic acidosis, which promptly resolved following rehydration and biotin administration. The results of the organic urine profile confirmed multiple carboxylase deficiency, and genetic testing revealed a novel pathogenic variant in the HLCS gene (NM_000411.8) in the homozygous state: c.995A>G; p.(Gln332Arg). No further decompensation was observed for her during the 3-year follow-up period. His older brother was diagnosed at the age of 23 years-old through biochemical tests, without any history of acidotic decompensation. A mini-review of HCS deficiency with late onset (>1 year) or early onset (<1 month) revealed that splice variants are associated with late onset, while both variants p.(Leu216Arg) and p.(Leu237Pro) are associated with early onset. However, the majority of genotypes do not show a clear correlation with the timing of HCS deficiency onset. The most significant point here is the description of extremely late-onset cases of HCS deficiency. This can prompt metabolic investigations and raise suspicion of this rare disease in cases of unexplained metabolic acidosis, even beyond early childhood.
Keywords: Inherited metabolic disease, Holocarboxylase synthase deficiency, Late onset, acidose métabolique, Biotine
Received: 28 Jun 2023; Accepted: 28 Aug 2024.
Copyright: © 2024 Lebreton, Gaschignard, MESLI, REDONNET, DOMENACH, ROCHE, DELPHINE and RICHARD. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Louis Lebreton, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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