COMBINED DEFICIENCY OF PYRUVATE DEHYDROGENASE AND MITOCHONDRIAL RESPIRATOR CHAIN COMPLEX I: CASE REPORT

Abstract

We described a male child of two years and three months affected by assial hypotonia, psicomotor retardation, muscular distal hypotrophy with hyporeflexia, dystonic movements and deafness. He was born from non‐consanguineous parents by spontaneous caesarian twin delivery at 38 weeks. His sister is healthy. He came to our observation at 16 months of age. Screenings for metabolic diseases and CSF neurotransmitters and lactate were normal, whereas the serum lactate was mildly increased. Brain MRI showed delayed myelination, with the normal lactate at the spectroscopic study. EEG showed interemispheric asymmetry with epileptic discharges. EMG showed a neurogenic pattern. Molecular DNA analysis for Spinal Muscular Atrophy was negative. Muscle biopsy showed neurogenic injury and an absence of ragged red fibers; enzymatic assay showed a severe deficiency of Complex I (2.8 nmol/min/mg protein, n.v. 17–33) and a mild deficiency of Pyruvate Dehydrogenase (PDHC=0.47 nmol/min/mg protein, n.v.0.8‐2).The clinical features of patients with a dysfunction in mitochondrial metabolic pathways are variable. A PDHC deficiency leads to a graduated spectrum of neurological involvement starting from severe forms with death in the neonatal period, Leigh disease and carbohydrate‐induced episodic ataxia. The most common features associated with a PDHC defect are delayed development and hypotonia. Patients with Complex I deficiency show a variable phenotype from fatal infantile encephalomyopathy to adult‐onset myopathy; neurodegenerative disorders are also described: Parkinson's disease, dystonia and Leber's optic neuropathy. A combined PHDC and Complex I deficiency is rarely reported. We can make the hypothesis that a defect of a single enzyme (Complex I) can play a role on the other enzyme deficiency. The presence of a primitive PHDC and Complex I deficiency is unlikely be hypothesized since the parents are not consanguineous and a double genetic defect is improbable.