Homocystinuria

Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. The most common form of the condition is caused by the lack of an enzyme called cystathionine beta-synthase. This form of homocystinuria is characterized by dislocation of the lens in the eye, an increased risk of abnormal blood clots, and skeletal abnormalities. Problems with development and learning are also evident in some cases.

Less common forms of homocystinuria are caused by a lack of other enzymes involved in processing amino acids. These disorders can cause intellectual disability, seizures, problems with movement, and a blood disorder called megaloblastic anemia.

Homocystinuria caused by cystathionine beta-synthase deficiency affects at least 1 in 200,000 to 335,000 people worldwide. The disorder appears to be more common in some countries, such as Ireland (1 in 65,000), Germany (1 in 17,800), Norway (1 in 6,400), and Qatar (1 in 3,000). Other forms of homocystinuria are much rarer, with a small number of cases reported in the scientific literature.

Mutations in the CBS, MTHFR, MTR, and MTRR genes cause homocystinuria.

The CBS gene provides instructions for producing cystathionine beta-synthase. This enzyme is responsible for one step in a chemical pathway that processes the amino acid methionine. Other amino acids, including homocysteine, are also products of this pathway. Mutations in the CBS gene disrupt the function of cystathionine beta-synthase, preventing homocysteine from being used properly. As a result, this amino acid and other potentially toxic substances build up in the blood, and some of the excess homocysteine is excreted in urine.

Rarely, homocystinuria can be caused by mutations in several other genes. The enzymes made by the MTHFR, MTR, and MTRR genes play roles in converting homocysteine back to methionine. Mutations in any of these genes prevent the enzymes from functioning properly, which leads to a buildup of homocysteine in the body.

Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.

Read more about the CBS, MTHFR, MTR, and MTRR genes.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Although people who carry one mutated copy and one normal copy of the CBS gene do not have homocystinuria, they are more likely than people without a CBS mutation to have vitamin B12 and folic acid deficiencies.