Dados do Trabalho

Título

NATURAL HISTORY OF DUCHENNE MUSCULAR DYSTROPHY WITH NONSENSE TYPE MUTATION

Introdução

A nonsense mutation results in a premature stop codon in the protein-coding region of the mRNA, interrupting ribosomal translation before a full-length functional dystrophin is generated.
This is a retrospective cohort analysis of a single Brazilian center of boys with mMDD over the last 15 years to establish natural history data for this group.

Objetivo

The objectives of this report were to clarify whether patients with DMMD diverge from the natural history of DMD: 1) in age of first clinical manifestations, diagnosis, neurodevelopmental abilities; 2) age at loss of ambulation and timed motor tests; 3) age of respiratory and heart failure; and 4) genotype-phenotype correlation.

Método

An analytical and descriptive, observational, retrospective study of the last 15 years was carried out on 25 patients with DMMD without disease-modifying treatments (Ataluren), aged between 1 and 22 years, referred to UFRJ. Nonsense DMD clinical data were obtained from retrospective medical records of 196 general DMD patient databases. The diagnosis of DMD was defined based on the DMD gene mutation and phenotype. Inclusion criteria were available clinical and genetic information and absence of a history of other systemic diseases.

Resultados

Family history was positive in 44% and 37% had immunohistochemical confirmation of lack of dystrophin on muscle biopsy plus genetic testing. Parents' perception of the first symptoms was noticed at 4.8 years of age: gait problems (32%), late walking (28%) and frequent falls (20%), but diagnostic confirmation was completed only at 6.8 years of age. . Late motor and language milestones were observed, as well as a high rate of intellectual disability (80%). 68% of boys lost their ability to walk and 24% died in the last 15 years, mainly due to cardiac events or complications from COVID infection

Conclusão

The Brazilian nmDMD cohort is very similar to all other DMD genotypes. Despite this, statistical evaluations revealed that the prognostic factors of nmDMD were worse than expected. The decline in respiratory, cardiac, and motor functions is inexorable even with standard care and without disease-modifying treatment.
In the absence of curative and disease-modifying treatment options available in the public health system, early diagnosis, genetic counseling for the patient and their families and adherence to standard care should be goals to be achieved in the near future, as a commitment between the government and the medical society.

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Palavras Chave

duchenne; ataluren; nonsense