Nervous system presentations in 42 children with mitochondrial disorders were analyzed by reviewing charts at the Wolfson Medical Center, Holon, and other centers in Israel. Mean age was 8 years; 2.8 yrs at presentation and 4.8 at diagnosis. Six died with neurologic deterioration, 4 of Leigh disease. Nervous system involvement was the first clinical presentation in 28 (66%) children: mental retardation or developmental delay occurred in 24; hypotonia in 18; autonomic manifestations in 18; seizures (generalized tonic-clonic) in 12; microcephaly in 12; cerebellar ataxia in 8; and choreoathetosis in 6 children. Unusual manifestations were stroke-like episodes in only 4; and headache, external ophthalmoplegia, autism, and hyperexplexia. Twenty five had an acute regression or progressive encephalopathy. Myopathy occurred in only 6.
Autonomic symptoms included gastrointestinal dysmotility and dysphagia in 6, central apnea in 6, cardiac irregularities in 4, neurogenic bladder in 3, and alternating anisocoria in 2.
Optic atrophy (5), retinitis pigmentosa (3), and sensorineural deafness (7) were presenting sensory signs.
CT or MRI in 33 patients showed hypodensities in the basal ganglia, thalamus, or brain stem in 7 patients, leukodystrophy in 2, hemiatrophy in 2, cerebral atrophy in 15 and cerebellar atrophy in 2. 
COMMENT. The most common neurologic presentations of mitochondrial disorders in children are developmental delay, abnormal muscle tone, and seizures, whereas characteristic symptoms including stroke-like episodes and ophthalmoplegia are rare. Unusual features include autism and hyperexplexia. In children presenting with a variety of complex neurologic symptoms, normal intelligence and normal serum lactic acid levels should not preclude a workup for mitochondrial disease.