Homocystinuria

What is homocystinuria?

Homocystinuria is an inherited disorder in which the body is unable to process certain amino acids (the building blocks of proteins) 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 mental retardation, seizures, problems with movement, and a blood disorder called megaloblastic anemia.

How common is homocystinuria?

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 Ireland. Other forms of homocystinuria are much rarer, with a small number of cases reported in the scientific literature.

What genes are related to homocystinuria?

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

Cystathionine beta-synthase is made by the CBS gene. This enzyme is responsible for one step in a chemical pathway that processes the amino acid methionine. Other amino acids, including homocysteine, are also involved in 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.

How do people inherit homocystinuria?

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.

Homocystinuria on Wikipedia

'''Homocystinuria''', also known as ''Cystathionine beta synthase deficiency'', is inherited disorder of the metabolism of the amino acid methionine. It is inherited an autosomal recessive trait, which means the child is to inherit the defective gene from both parents. This defect leads to a multisystemic disorder of the connective tissue, muscles, CNS, and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normals and early symptoms, if any are present, are vague.

Symptoms

*A family history of homocystinuria *Nearsightedness *Flush across the cheeks *Tall, thin build *Long limbs *High-arched feet (pes cavus) *Knock-knees (genu valgum) *Pectus excavatum *Pectus carinatum *Mental retardation *Psychiatric disease

Mortality/morbidity

The life expectancy of patients with homocystinuria is reduced. It is known that before the age of 30, almost one fourth of patients die as a result of thrombotic complications(e.g. heart attack).

Treatment

No specific cure has been discovered for homocystinuria. However, many people are treated to high doses of vitamin B6(also known as pyridoxine). Slightly less than 50% respond to this treatment and are needed to intake supplemental vitamin B6 for the rest of their lives. Those that do not respond require a low methionine diet, and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally added cysteinein the diet is helpful.

Recommended diet

Low-protein food is recommended for these disorder requires food products which are low in particular types of amino-acid (i.e. methonine) [ Read More ]

External Resources

NORD: Homocystinuria - Offers alternative names, a general discussion and further resources.

Drkoop: Medical Encyclopedia: Homocystinuria - An in depth look at this disorder, including a definition, the causes and risk factors, symptoms, prevention, complications, prognosis, diagnosis and treatment.

Genetic Disorders: The Links to Diet - Explores the role of diet in birth defects and genetic disorders. Includes nutritional links to disorders such as Down syndrome, cerebral palsy, homocystinuria, and cystic fibrosis.