ClinVar

In a family in which the proband had a progressive neurologic disorder and his brother died in infancy of Leigh syndrome (256000), Santorelli et al. (1997) identified a 1-bp insertion (5537insT) in the MTTW gene. Muscle biopsy from the proband showed subsarcolemmal proliferation of mitochondria and decreased activities of oxidative metabolism enzymes, in particular complex IV. The mutation was abundant in tissues from the proband and his brother (greater than 92%), and less abundant (42 to 89%) in 4 maternal relatives, 3 of whom had neuropsychiatric disturbances.

Tulinius et al. (2003) reported a boy with Leigh syndrome who had the 5537insT mutation. From infancy, he was irritable and had hypotonia. Later, neurologic features included nystagmus, optic atrophy, seizures, delayed motor development, and mental retardation. Skeletal muscle analysis showed a profound COX deficiency and complex I deficiency. The mutation was found in a high proportion (greater than 95%) in blood, liver, and muscle tissue of the patient, and in blood of the patient's mother (81%).