Title:Metabolic Myopathies: Experience of a Reference Center of Inherited Metabolic Diseases
Volume: 24
Issue: 16
Author(s): Mafalda Rebelo*, Madalena Pires, Laura Azurara, Lara Câmara, Márcia Pereira, Augusto Ribeirinho, Gonçalo Padeira, Patrícia Gaspar Silva, Sandra Jacinto, José Pedro Vieira and Ana Cristina Ferreira
Affiliation:
- Centro Hospitalar de Lisboa Central Pediatric Neurology Unit, Pediatrics Department, Hospital Dona Estefânia Lisbon Portugal
Keywords:
metabolic myopathies, glycogenosis, fatty acid, mitochondrial diseases, fatty acid oxidation disorders, rhabdomyolysis
Abstract: Introduction: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders
affecting metabolic pathways involved in energy production during rest, exercise and
physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/
glycogenolysis, fatty acid transport/oxidation or in the 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 the set of clinical manifestations for which a high level of suspicion is important.
Methods: Retrospective descriptive study of the clinical, biochemical, and molecular features 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 varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed
by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were 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 heterogeneous 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.
