Complex mitochondriopathy associated with 4 mtDNA transitions

In a 33-year-old man, mitochondriopathy was diagnosed upon short stature, auditory impairment, gynaecomastia, hypogonadism, vertical ophthalmoplegia, cerebral atrophy, leucencephalopathy, cataract, hypertrabeculated left ventricle, hypothyroidism, diabetes mellitus, glomerulonephritis necessitating kidney transplantation, general wasting, polyneuropathy, abnormally high lactate levels on exercise, partially reduced cytochrome-c oxidase staining and abnormally structured mitochondria on muscle biopsy. Mitochondrial DNA (mtDNA) analysis revealed 1 novel (A15662G) and 3 known mtDNA transition(s) (T3398C, T4216C, G15812A) affecting the cytb and ND1 gene, respectively. Three of the patient's transitions were also detected in blood leukocytes of the patient's maternal grandmother, mother and brother. Mutant mtDNA was heteroplasmic at >75% in the patient's skeletal muscle.