A novel mutation in the ubiquinol-cytochrome c reductase synthesis-like gene associated with complex III deficiency and Björnstad syndrome: A case report.

Abstract

Rationale:The ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene is located on chromosome 2 (2q35) and encodes an ATPase that is associated with various cellular activities and is embedded in the mitochondrial inner membrane; this ATPase is presumed to facilitate the insertion of the Rieske Fe/S protein into precursors of Complex III (CIII) during the assembly of the respiratory chain. We report the first case of a compound heterozygous mutation in the BCS1L gene in China.Patient concerns:A 7-month-old girl presented with a 3-month history of psychomotor developmental retardation and a 1-month history of epilepsy combined with parallel psychomotor developmental deterioration. The clinical manifestations in the patient included psychomotor developmental retardation, infantile spasms, pili torti, tubulopathy, hepatic pathologies and lactic acidosis.Diagnosis:Combined with her clinical presentation, the patient was diagnosed with CIII deficiency and Björnstad syndrome caused by a novel mutation in the BCS1L gene after molecular biological examination. Whole exome sequencing revealed a compound heterozygous mutation with a missense mutation (c.548G > A/p. R183H) inherited from her mother and an insertion mutation (c.1061_1062insCTA/p. G354delinsGY) inherited from her father.Interventions:Before admission, the patient had received oral topiramate for 1 month. After admission, additional intravenous arginine hydrochloride was administered for five days in the acute metabolic disorder phase, and persistent cocktail therapy was introduced, including coenzyme Q10 (20 mg/d), carnitine (1 g/d) and vitamins (vitamin B1, vitamin B2, vitamin B6, and vitamin C).Outcomes:The spasm seizures were decreased by 50% after 2 weeks of treatment. The blood ammonia, myocardial enzyme and urine glucose levels declined to normal levels. At a 1-month follow-up, the patient improved clinically with a decrease in spasm seizures of 75%, stronger sucking and more voluntary activities. However, she still had mild lactic acidosis and mild hepatic damage.Lessons:We reported the first patient with CIII deficiency and Björnstad syndrome in China and identified 1 novel mutation (C.1061_1062insCTA and P. G354delinsGY) in the BCS1L gene. This finding expands the BCS1L gene mutation profile and will be beneficial for genetic diagnosis.