Cerebellar hypoplasia in respiratory chain dysfunction.

Disruption of early or late fetal brain development resulting in structural abnormalities may be associated with inborn errors of mitochondrial metabolism. It is common in patients with deficiency of pyruvate dehydrogenase activity and it has sporadically been described in patients with dysfunction of the tricarboxylic acid cycle. Mitochondrial respiratory chain disorders are not commonly known to interfere with early brain development. We describe here a girl with an encephalomyopathy likely to be due to a novel type of deficiency of cytochrome c oxidase (complex IV) activity that presented with severe hypotonia, myoclonic seizures, optic atrophy and elevated lactate concentration in cerebrospinal fluid shortly after birth. Cranial magnetic resonance imaging revealed hypoplasia of the cerebellum with rudimentary cerebellar hemispheres and relative sparing of the vermis. This case suggests that deficiency of cytochrome c oxidase and possibly respiratory chain disorders in general have to be considered in the differential diagnosis of cerebellar hypoplasia.