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Título

Congenital fiber type disproportion due to homozygous HACD1 mutation: A case report

RESUMO

Congenital myopathies are a broad group of pathologies whose symptoms include hypotonia, proximal weakness, distinct phenotypic features, and wide variation in severity. Its histological findings are important and helped in its classification. Currently, however, with the advent and easier access to genetic testing by next generation sequencing (NGS), knowledge about the pathophysiological bases of these diseases has expanded greatly.

We report the case of a 66-year-old male patient whose symptoms started at birth with hypotonia and, subsequently, gait delay (walked independently at 7 years of age). After childhood there was stability of symptoms, with slight worsening after the fifth decade, when we started to follow him up.

In the initial assessment proximal weakness, mainly in the lower limbs, winged scapula and myopathic gait were noticed. There were frequent falls, and difficulty climbing stairs. There were no bulbar symptoms, sensibility or coordination impairment, myotonic phenomenon, joint hypermobility, cicatrization impairment or skin lesions.

The patient's parents were consanguineous (first degree cousins), and there was a history of premature death of a sister from an uninvestigated neuromuscular disease.

Aldolase and creatine phosphokinase levels were normal. Further investigation with nerve conduction study and electromyography showed a proximal myopathic pattern and muscle biopsy sampling the left biceps brachii showed congenital fiber type disproportion. No necrosis, interstitial fibrosis or inflammatory infiltrate were found. Echocardiogram and electrocardiogram showed no abnormalities.

The patient was subsequently tested with a broad genetic NGS panel for neuromuscular diseases, and a homozygous mutation in the HACD1 gene (c.373_375+2del) was found (classified as probably pathogenic according to ACMG criteria). Additionally, a heterozygous pathogenic mutation in the COL6A2 gene was identified. As mentioned above, however, the patient did not have phenotypic characteristics compatible with mutations in collagen 6 gene.

To date, few cases of myopathy caused by HACD1 mutations have been described worldwide and, as far as we are aware, this is the first case of HACD1 mutation related myopathy reported in Brazil. By reporting this case, we expect to contribute to expanding the knowledge of this congenital myopathy and bring it to attention as a possible cause of congenital myopathy in our country.