Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil

Abstract

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Resumo

Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.

Keywords

Muscular Diseases - Carnitine O-Palmitoyltransferase - Lipids - Genetics

Palavras-chave

Doenças Musculares - Carnitina O-Palmitoiltransferase - Lipídeos - Genética

Authors' Contributions

PJL: conceptualization, data curation, formal analysis, investigation, methodology, project administration, validation, writing-original draft, writing-review & editing; CSKK: investigation, writing-review & editing; RDD, OHF, PRVPR: writing-review & editing; RCA: methodology, writing-review & editing; RHS: formal analysis, funding acquisition, investigation, methodology, writing-review & editing; LCW: investigation, writing-review & editing.

Support

This study was supported by UFPR and genetic analysis was partially supported by PTC Therapeutics (Brazil).

Publication History

Received: 12 September 2023

Accepted: 15 December 2023

Article published online:
23 February 2024

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