Objective: To define the clinical and biochemical abnormalities of an autosomal dominant form of acute encephalopathy.
Methods: The clinical details of 11 affected family members in comparison with 63 unaffected relatives were analyzed.
Results: Affected children become comatose after onset of a febrile illness. Outcomes include full recovery, permanent neurologic impairment, and death. Recurrences produce more severe impairments. Lesions of necrotizing encephalopathy of the thalamus and brainstem are present on autopsy and MRI. Oxidative phosphorylation of intact mitochondria from a muscle biopsy shows loose coupling. Unaffected family members, including obligate carriers, share no clinical characteristics, demonstrating incomplete penetrance.
Conclusions: Characteristic pathology and MRI findings define this disorder of autosomal dominant acute encephalopathy. Leigh syndrome and sporadic acute necrotizing encephalopathy share similarities but are distinct.