De novo mutation in the mitochondrial tRNA(Leu(UUR)) gene (A3243G) with rapid segregation resulting in MELAS in the offspring

A 14-year-old Chinese boy with a normal perinatal and early developmental h istory presented at 5 years of age with migraine, intractable epilepsy, ata xia, supraventricular tachycardia, paralytic ileus and progressive mental d eterioration. Computerized tomography revealed multiple cerebral infarcts i n the parieto-occipital region without basal ganglial calcification. Magnet ic resonance imaging showed increased signal intensity in T2 weighted image s in the same regions. A cerebral digital subtraction angiogram was normal. Venous lactate, pyruvate, lactate to pyruvate ratio and cerebrospinal flui d lactate were elevated. Muscle biopsy did not reveal any ragged red fibres ; dinucleotide-tetrazolium reductase activity was normal. Mitochondrial DNA analysis detected an adenine to guanine mutation at nucleotide position 32 43 of tRNA(Leu(UUR)). All four tissues analysed demonstrated heteroplasmy: leucocyte 56%, hair follicle 70%; buccal cell 64%; muscle 54%. The mother a nd brother of the proband, both asymptomatic, were also found to have a het eroplasmic A3243G mutation in the leucocytes, hair follicle and buccal cell s. Other members of the maternal lineage, including the maternal grandmothe r, did not have the mutation. This report describes a patient with mitochon drial encephalopathy, lactic acidosis, stroke-like episodes, who presented with multisystem involvement. The absence of ragged red fibres in muscle bi opsy did not preclude the diagnosis. Mutational analysis of mitochodrial DN A conveniently confirmed the diagnosis of the disorder. A de novo mutaton i s demonstrated in this family.