Miopatías por defectos en la beta oxidación de ácidos grasos. Deficiencia de 3-hidroxiacil CoA-deshidrogenasa de cadena larga/complejo proteico trifuncional mitocondrial LCHADD/TFP una entidad con tratamiento específico

Abstract

The b-oxidation of fatty acids is a critical physiological process that allows the use of fat as a source of energy in times of stress and fasting. Isolated long-chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHADD) (OMIM#609016) is an autosomal recessive disease that affects the metabolism of long-chain fatty acids and is secondary to mutations in the HADHA gene. Clinical symptoms are heterogeneous and develop progressively with exacerbation episodes mainly during episodes of intercurrent illness or fasting due to increased energy needs. A 36-year-old patient presented with progressive weakness in both lower limbs with distal onset and proximal progression associated with episodes of rhabdomyolysis that are triggered by a febrile syndrome. Clinical examination demonstrated the presence of surgical ankylosis of the ankle joint, weakness when flexion of the thigh over the pelvis 4/5 and flexion of the leg over the thigh 4/5, muscle hypotonia and posterior compartment muscle atrophy of the leg, areflexia of the lower limbs with preserved reflexes in the upper limbs. Given the suspicion of a possible metabolic myopathy, a dosage of acylcarnitines is requested where an increase in C16OH, C18OH, C18:20H and C18:10H is observed, and given these results, the HADHA gene is evaluated, demonstrating the presence of the variant c.2231delT, which promotes a change in the reading matrix from this point on, with the consequent creation of a premature stop codon for protein translation. The diagnosis of LCHADD deficiency is established by demonstrating an elevation of long-chain fatty acids, hydroxyacylcarnitine species in plasma, and/or increased excretion of 3-hydroxy-dicarboxylic acids in urine in combination with identification of biallelic pathogenic variants in HADHA or HADHB by molecular genetic testing.