Subscribe to RSS
DOI: 10.1055/s-0044-1779508
Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil
Miopatia por deficiência de carnitina palmitoiltransferase II: atualizando os aspectos genéticos da primeira publicação no Brasil
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.
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
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Paulo José Lorenzoni, Cláudia Suemi Kamoi Kay, Renata Dal-Pra Ducci, Otto Jesus Hernandez Fustes, Paula Raquel do Vale Pascoal Rodrigues, Raquel Cristina Arndt, Rosana Herminia Scola, Lineu Cesar Werneck. Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil. Arq Neuropsiquiatr 2024; 82: s00441779508.
DOI: 10.1055/s-0044-1779508
-
References
- 1 Joshi PR, Zierz S. Muscle carnitine palmitoyltransferase II (CPT II) deficiency: a conceptual approach. Molecules 2020; 25 (08) 1784
- 2 DiMauro S, DiMauro PM. Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science 1973; 182 (4115) 929-931
- 3 Deschauer M, Wieser T, Zierz S. Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects. Arch Neurol 2005; 62 (01) 37-41
- 4 Martín MA, Rubio JC, De Bustos F. et al. Molecular analysis in Spanish patients with muscle carnitine palmitoyltransferase deficiency. Muscle Nerve 1999; 22 (07) 941-943
- 5 Taggart RT, Smail D, Apolito C, Vladutiu GD. Novel mutations associated with carnitine palmitoyltransferase II deficiency. Hum Mutat 1999; 13 (03) 210-220
- 6 Thuillier L, Rostane H, Droin V. et al. Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency. Hum Mutat 2003; 21 (05) 493-501
- 7 Joshi PR, Deschauer M, Zierz S. Carnitine palmitoyltransferase II (CPT II) deficiency: genotype-phenotype analysis of 50 patients. J Neurol Sci 2014; 338 (1-2): 107-111
- 8 Fanin M, Anichini A, Cassandrini D. et al. Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT-II deficiency. Clin Genet 2012; 82 (03) 232-239
- 9 Werneck LC, Boer CAA, Papadimitriou A, Di Mauro S. [Myopathy due to carnitine palmitoyltransferase deficiency. Report of 2 cases with enzymatic analyses on muscle tissue]. Arq Neuropsiquiatr 1983; 41 (04) 377-384 . Doi. 10.1590/s0004-282. Doi: × 1983000400008