Homocystinuria (CBS-Related) (CBS)
Homocystinuria (CBS-related) is an autosomal recessive disorder caused by pathogenic variants in the gene CBS, and while it is considered to be a pan-ethnic disorder, it is most commonly seen among those of Qatari and Caucasian ancestry. Symptoms include intellectual disability, dislocated lenses of the eye, blood clots, brittle bones, and other skeletal abnormalities. The severity of the symptoms varies significantly. Some individuals with the more severe disease, known as the B6-non-responsive type, develop symptoms during infancy, while others with the milder B6-responsive disease may not clinically develop symptoms until childhood or early adulthood. The majority of affected individuals have a shortened lifespan due to the lack of effective treatment. Affected infants must be on a methionine-restricted diet in order to reduce the reduce symptoms and possibility of seizures. Several specific variants have been associated with milder or more severe disease phenotypes, and therefore the disease severity may be predicted in some individuals based on the variants inherited.
For information about carrier frequency and residual risk, please see the residual risk table.