m.3243A> T carriers require repeated prospective multisystem examinations not to overlook subclinical organ involvement

Abstract

We comment on the article by Gillespie et al. about a 19-year-old man with a non-syndromic multisystem mitochondrial disorder (MID) due to the m.3243 A > T variant in MT-TL1, which he had inherited from his mother. The patient manifested clinically in the brain (epilepsy, cerebellar ataxia, headaches, basal ganglia calcification, cerebral atrophy, cognitive decline), in the eyes (cataracts, pigmentary retinopathy), in the ears (hypoacusis), in the endocrine organs (growth retardation, hypogonadism), intestines (motility disorders, vomiting), kidneys (nephrotic syndrome), heart (atrial septal defect, arterial hypertension), and muscles (myopathy, lactic acidosis). At the age of 19, he was admitted to palliative care and died. In summary, carriers of the m.3243 A > T variant should be prospectively examined for multisystem involvement, organs already clinically affected should be examined repeatedly so as not to overlook subclinical progression, and that all first-degree relatives should be genetically tested to assess genetic and phenotypic heterogeneity during segregation.