Non lactate acidotic encephalomyopathy with ptosis, severe central apnea, isolated complex III deficiency and 15257 mutation in the cytochrome b gene – a previously undescribed mitochondrial disorder constellation

Objective: Mitochondrial disorders can present with a wide variety of clinical signs and symptoms and the number of genes known to be envolved is still increasing.

Methods: We report on three siblings who uniformly present with generalized muscular hypotonia and severe apnea conditions within the first weeks of life leading to long term mechanical ventilation. In the further course they developed massive statomotor retardation with muscular hypotonia and ptosis as well as massive cognitive retardation (imbecility).

Results: All three patients had no lactic acidosis, neither in blood nor in CSF, nor in the apnea situation, nor when challenged with glucose. MRI showed global brain atrophy. The measurement of respiratory chain enzyme activities in “fresh/warm“ muscle biopsies (within 2 hours after explantation) finally revealed clearly decreased complex III activities. Genetic work up of the three siblings with sequence analysis showed the same homoplasmic 15257G>A mutation in the coding region of the cytochrome b gene, sometimes found in Hereditary Optic Neuropathy.

Conclusion: This is a previously undescribed, non lactate acidotic mitochondrial disorder constellation, that should be considered especially in long term respirator dependent patients with encephalomyopathy of unknown origin.

Keywords: mitochondriopathy, complex III, 15257 mutation, cytochrome b gene, apnea