1 - Unidade de Neuropediatria, Área de Pediatria, Centro Hospitalar Universitário de Lisboa Central
2 - Área de Pediatria, Centro Hospitalar Universitário de Lisboa Central
3 - Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central
4 - Área de Medicina, Centro Hospitalar Universitário de Lisboa Central
- Poster no Congresso da Sociedade Portuguesa de Doenças Metabólicas (Figueira da Foz, 19 a 31 de março de 2023)
- Resumo em Revista: Endocr Metab Immune Disord Drug Targets. 2023 Oct 18
Introduction: Metabolic myopathies (MM) are a heterogenous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever or fasting). Impairments in the pathways of glycolysis/glycogenolysis, fatty acid transport/oxidation or in mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in set of clinical manifestations, for which a high level of suspicion is important.
Methods: Retrospective descriptive study of the clinical, biochemical, and molecular data of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central, from 2009 to 2022.
Results: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages vary from 15 months through 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 are asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy.
Conclusion: MM are a heterogenous set of disorders but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.
Palavras Chave: metabolic myopathies; glycogenosis; fatty acid; mitochondrial diseases