Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature

Abstract

Background Mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome is one of the most well‐known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi‐systemic phenotype that predominantly features neurological manifestations––stroke‐like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses. Methods A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed. Results Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke‐like episodes. Heteroplasmy is higher in a tissue other than blood in most cases. Conclusion The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.

Mitochondrial Chronic Progressive External Ophthalmoplegia

“…Less commonly, it can present with gastrointestinal manifestations that include gastric perforation, ischemic colitis, segmental ileal paralysis, pseudo-obstruction, or megacolon. Endocrine manifestations, such as diabetes mellitus, have also been reported in MELAS [44].…”

Síndrome de Melas: reporte de caso pediátrico

“…Cefalea tipo migrañosa, debilidad muscular y alteraciones visuales (62%). Retraso del neurodesarrollo (50%) y déficits auditivos como la hipoacusia neurosensorial (26%) (13). Todos estos síntomas estuvieron presentes en nuestra paciente.…”

“…Las enfermedades mitocondriales se han asociado durante mucho tiempo con la diabetes, incluso se incluyó en la descripción inicial del síndrome de MELAS (13,18) Se ha reportado hasta en un tercio de todos los pacientes. La diabetes llamada MIDD (Maternally inherited diabetes and deafness) "diabetes y sordera hereditaria materna", es causada por mutación en el ADN mitocondrial (19).…”

“…Otra manifestación sistémica del síndrome es la falta de crecimiento; se ha informado talla baja entre el 33% y 82% de los pacientes. Ocasionalmente se han informado otros informes de disfunción endocrina en pacientes con síndrome MELAS, como: hipotiroidismo, hipoparatiroidismo e hipogonadismo hipogonadotrópico (9)(10)(11)(12)(13). Se han descrito manifestaciones más raras del síndrome MELAS que afectan a otros sistemas de órganos.…”

“…La neuropatía sensitivo motora periférica es una manifestación a menudo subclínica, afecta típicamente a los miembros inferiores distalmente y es progresiva. La disfunción del músculo liso gastrointestinal provoca: estreñimiento, diarrea, dismotilidad intestinal y pseudoobstrucción intestinal (13). Las manifestaciones renales notificadas incluyen glomeruloesclerosis focal y segmentaria, proteinuria nefrótica e insuficiencia renal (20).…”