Following this study we propose guidelines for screening and for the management of confirmed cases.

Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-012-9492-z) contains supplementary material, which is available to authorized users.

Focal-onset seizures and encephalopathy are prominent Background: features of a stroke-like episode, which is a severe neurological manifestation associated with subtypes of mitochondrial disease. Despite more than 30 years of research, the acute treatment of stroke-like episodes remains controversial.We used the modified Delphi process to harness the clinical Methods: expertise of a group of mitochondrial disease specialists from five European countries to produce consensus guidance for the acute management of stroke-like episodes and commonly associated complications.Consensus on a new definition of mitochondrial stroke-like Results: episodes was achieved and enabled the group to develop diagnostic criteria based on clinical features, neuroimaging and/or