Sirs: Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa (NARP) and severe infantile subacute necrotising encephalomyopathy (Maternally Inherited Leigh Syndrome, MILS) are the main clinical syndromes of a maternally inherited mitochondrial disorder caused by a point mutation in the nucleotide position 8993 of the mitochondrial DNA (mtDNA), in the ATPase6 gene. The most common mutation is a heteroplasmic T8993G transversion, a few cases being associated with a T8993C transition [1,5]. Different phenotypes can coexist in the same family [8]. Proton magnetic resonance spectroscopy (1H-MRS) allows non-invasive measurement of brain metabolites in patients with mitochondrial disorders [4,7]. We report a new case of familial T8993C transition causing both the NARP and the MILS phenotype in the same generation.Case report -A 27 year old woman from central Italy came to our observation with a 20-year history of slowly progressive psychomotor retardation. Delivery was vaginal, but complicated by placental dysfunction (weight at birth = 1.8 kg). She did well until the age of seven years when she had measles and began to show gait unsteadiness, fatigability and frequent falls. She had two episodes of brief loss of consciousness. Neurological examination revealed generalised hypotonia, muscle weakness, ataxic gait, reduced tendon reflexes, and finger-to-nose dysmetria. A diagnosis of postmeasles encephalitis was made and antiepileptic treatment (sodium valproate) started. Ataxia and muscle weakness slowly progressed and, in addition, learning difficulties were noticed at school. At age 25 years she was diagnosed as having sensorineural hypoacusia and retinitis pigmentosa. In our hospital, neurological examination showed proximal muscle weakness, generalised hypotonia, reduced tendon reflexes, bilateral Babinski sign, standing unsteadiness, truncal and gait ataxia, finger-to-nose and heel-to-knee dysmetria. Neuropsychological tests disclosed an acquired selective mental retardation (memory, comprehension). EMG was myopathic, brain MRI showed ponto-cerebellar atrophy (Fig. 1B) and EEG bitemporal slow wave activity. Blood lactate was normal, ECG showed sinusal tachycardia with AV conduction in the low normal range. Her only sister had died of cardiac arrest, in 1989, at age 3 years, after a one month history of progressive deterioration of consciousness, respiratory insufficiency, epileptic seizures and hyperthermia. Brain MRI revealed bilateral T2 hyperintense areas in the basal ganglia, lamina quadrigemina, caudate nucleus, posterior bulb, and in periventricular grey and in hemispheric white matter. CSF lactate was increased (46 mg/dl = 5.1 mmol/L, normal values = 10.9-17.2 mg/dl, or 1.2-1.9 mmol/L; serum lactate was normal = 12.3) These findings had led to a diagnosis of subacute necrotising encephalopathy. The 49 year old mother was short, affected with hypothyroidism. Her clinical examination revealed clinical signs of peripheral neuropathy. The remaining family history was not significant (Fig. 1A).The proband's s...

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Six years before the present study we performed a retrospective study of 114 subjects presenting with asymptomatic / oligosymptomatic hyperckemia (raised creatine kinase blood levels), a diagnosis being made in 21 of them. We now present the results of a long-term follow-up in 55 of the still undiagnosed 93 individuals. Most of them have remained asymptomatic and did not develop specific neuromuscular disorders. One subject became frankly symptomatic manifesting limb-girdle weakness. A diagnosis of dystrophinopathy carrier and one of possible type I SMA carrier were indirectly made in another two subjects. Almost all subjects still have hyperckemia, though the mean creatine kinase (CK) value is lower than before. CK levels have become normal in 12 subjects. Two died of neoplasia, and six developed non-neuromuscular disorders. We noted no follow-up differences in terms of CK modifications between subjects with pathological EMG and/or muscle biopsy findings and those with normal findings at first examination.

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