A mitochondrial DNA micro deletion in a newborn girl with transient lactic acidosis.

A full term 2.9 kg baby girl born to healthy non-consanguineous Caucasian parents developed dehydration, hypothermia, hypotonia and convulsions on day 3. Hyperlactactemia -ranging from 3.9 to 7.1 mmo/L- and compensated metabolic acidosis (pH 7.29 - 7.31) were found along with normal pyruvatemia. A brain MRI demonstrated a sub-arachnoid haemorrhage at the level of the occipital region and posterior fossa. Initial treatment with intravenous fluids, Phenobarbital and L-carnitine was started, but lactic acidosis persisted during 3 weeks before normalisation. An episode of supra-ventricular tachyarrythmia demanded propranolol treatment. Histochemical studies on a muscle needle biopsy sample and biochemical studies in fibroblasts demonstrated deficiency of complex IV. Electron microscopy of the muscle biopsy sample disclosed structurally abnormal mitochondria. Routine analysis of mtDNA ruled out the presence of large-scale deletions and common point mutations for MELAS, MERRF and NARP. However, SSCP analysis of the ATPase6 gene revealed an alterated mobility pattern. Direct sequencing identified a 2 bp homoplasmic deletion located at nt 9205-9206. The deletion removes the TA translation stop codon of the mt ATPase6 gene, predicting a read through of the messenger in frame with the COXIII gene. The child, now 16 months old, develops a psychomotor retardation, a failure to thrive and chronic lactic acidosis.