title: BCS1L gene mutation causing GRACILE syndrome: case report.
abstract: GRACILE syndrome is a rare autosomal recessive disease characterized by fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload, profound lactic acidosis, and early death. It is caused by homozygosity for a missense mutation in the BCS1L gene. The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III. Here we report that a homozygous mutation c.296C > T (p.P99L), in the first exon of BCS1L gene found in an affected 2-month-old boy of asymptomatic consanguineous parents results in GRACILE syndrome. This genotype is associated with a severe clinical presentation. So far no available treatments have changed the fatal course of the disease, and the metabolic disturbance responsible is still not clearly identified. Therefore, providing prenatal diagnosis in families with previous affected infants is of major importance. Mitochondrial disorders are an extremely heterogeneous group of diseases sharing, in common, the fact that they all ultimately impair the function of the mitochondrial respiratory chain. A clinical picture with fetal growth restriction, postnatal lactacidosis, aminoaciduria, hypoglycemia, coagulopathy, elevated liver enzymes, and cholestasis should direct investigations on mitochondrial disorder.
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Gazi University Hospital , Ankara , Turkey.
authors.forename: Çiğdem Seher
authors.initials: ÇS
authors.lastname: Kasapkara
authors.forename: Leyla
authors.initials: L
authors.lastname: Tümer
authors.forename: Fatih Suheyl
authors.initials: FS
authors.lastname: Ezgü
authors.forename: Aynur
authors.initials: A
authors.lastname: Küçükçongar
authors.forename: Alev
authors.initials: A
authors.lastname: Hasanoğlu
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000140:Acidosis, Lactic / Q000235:genetics*; D002779:Cholestasis / Q000235:genetics*; D014450:Electron Transport Complex III / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000235:genetics*; D006486:Hemosiderosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000151:congenital* / Q000235:genetics; D020125:Mutation, Missense; D000608:Renal Aminoacidurias / Q000235:genetics*
chemical_list: C435491:BCS1L protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III
keywords: Cholestasis; Fanconi type aminoaciduria; growth retardation; iron overload; profound lactic acidosis