GRACILE Syndrome and Other BCS1L-Related Disorders (BCS1L)

Pathogenic variants in the gene BCS1L have been reported to cause four different autosomal recessive disorders. GRACILE syndrome, which stands for growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death, is diagnosed most commonly in individuals of Finnish descent. Patients typically die in infancy. Mitochondrial complex III deficiency, nuclear type 1 manifests at birth. Features include lactic acidosis, failure to thrive, brain abnormalities, developmental delay and intellectual disability. Many patients die in childhood. Bjornstad syndrome is characterized by hearing loss that begins in childhood and sparse, brittle, light-colored hair. Some patients have been reported to have intellectual disability. Leigh syndrome is a progressive neurological disorder that usually manifests in infancy or childhood and is characterized by hypotonia, ataxia, seizures, vision abnormalities, and intellectual disability. Most patients die in childhood. Depending on the two pathogenic variants that an individual inherits, it may be possible to predict which of the above phenotypes is likely to develop. However, it may not be possible to predict the phenotype for all patients.

For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.