Muscle ultrastructure and histopathological findings in a Brazilian single-centre series of genetically classified telethoninopathy patients

Abstract Background Telethoninopathy or TCAP -gene related Limb Girdle Muscular Dystrophy is a rare genetic disease that was first described in Brazil. There are around 100 families reported worldwide. Due to its rarity, detailed information on muscle biopsy light and electron microscopic features are lacking. Cases presentation Retrospective study of consecutive muscle biopsies performed in patients from a Neuromuscular Outpatient Clinic between 2011 and 2023. Inclusion criteria: telethoninopathy diagnosed by both immunohistochemistry and molecular studies. Seven patients (0.7% or 7/953) were found: five male and two female, admitted from 6 to 54 years old. Detailed light and electron microscopy findings are illustrated. Muscle imaging is presented. A dystrophic pattern on muscle biopsy was found in 57% (4/7) of the patients. Other 43% (3/7) presented myopathic features such as variation in fibre calibre, nuclear internalization, rimmed vacuoles, and oxidative irregularities. Morphometry disclosed type 1 lobulated fibres that were 34%, 52%, and 57% smaller than type 2 fibres, respectively, in three patients, without type 1 fibre predominance. Electron microscopy demonstrated nuclear pseudoinclusions, pyknosis, multifocal loss of the sarcolemma, and 17 nm intrasarcoplasmic filamentous inclusions. All patients presented: (1) complete absence of the immunohistochemical expression of telethonin, and (2) the homozygous c.157C > T, p.(Gln53*) pathogenic variant in exon 2 of the TCAP gene. Conclusion Anti-telethonin immunohistochemistry may be helpful in unsolved cases with nonspecific myopathic abnormalities, specially with small type 1 lobulated fibres. Appropriate diagnosis is important for adequate genetic counselling.