GRACILE syndrome

GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death) syndrome is a devastating inherited disorder characterized by fetal growth retardation, iron overload in the liver, buildup of a chemical called lactic acid, elevated molecules called amino acids in the urine caused by kidney problems, and cholestasis (reduced production and release of bile). Affected infants normally do not live past the first several months of life, with about half only living a few days after birth. GRACILE syndrome is caused by pathogenic variants in the BCS1L gene.

GRACILE syndrome is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for GRACILE syndrome. However, the risk to have a child affected with GRACILE syndrome is increased. Testing of reproductive partners is recommended for carriers of GRACILE syndrome.

The majority of the affected individuals with GRACILE syndrome are people of Finnish decent. The estimated occurence in Finland is 1 in 47,000 newborns.

Genetics Home Reference: GRACILE syndrome (http://ghr.nlm.nih.gov)
Genetic Alliance: GRACILE syndrome (http://www.diseaseinfosearch.org/)

OMIM [GRACILE syndrome: 603358] (http://www.omim.org/)

• Full gene sequencing