Homocystinuria caused by cobalamin cofactor metabolism (cbl) defect occurs when the body cannot properly process cobalamin (vitamin B12). This activity is essential for converting an important amino acid—homocysteine—back to methionine, another important amino acid. When the body cannot process vitamin B12 as it should, blood levels of homocysteine increase, and blood levels of methionine decrease. This causes harmful symptoms to develop.
The body goes through a series of steps to process vitamin B12. Errors can occur in each of these steps. This leads to many types of cbl defects that cause homocystinuria: cblC, cblD, cblD variant 1, cblE, cblF, cblG, cblJ, and cblX.
By far the most common and best understood type of cbl defect is cblC defect. CblC defect causes two disorders: homocystinuria and methylmalonic acidemia (MMA). MMA occurs when methylmalonic acid builds up in the blood. The body makes tiny amounts of methylmalonic acid when digesting protein. But a high level of methylmalonic acid in the blood can also cause harmful symptoms to develop. CblD, cblF, cblJ, and cblX defects also cause both homocystinuria and MMA. These are known as combined disorders.
Homocystinuria without methylmalonic acidemia occurs in people with cblD variant 1, cblE, or cblG defect. These are known as single disorders.
Symptoms of homocystinuria caused by cblC defect can develop for the first time at any age and can vary greatly from person to person.
Most people with cblC defect develop signs and symptoms before they are a year old. This is the “early-onset” form of cblC defect. Symptoms that may develop include:
People with a milder form of cblC defect may not develop symptoms until later in life—from childhood to adulthood. This is the “late-onset” form of cblC defect. Symptoms that may develop include:
Most states screen newborns for cbl defects with combined homocystinuria and methylmalonic acidemia, such as cblC and cblD, by looking for markers in the blood caused by high levels of methylmalonic acid (MMA). To learn if this test is offered in your state, visit babysfirsttest.org.
If someone has a positive newborn screen and/or symptoms that could be signs of homocystinuria caused by a cbl defect, your doctor will order lab tests. The following results may point to a positive diagnosis for most types of cbl defect, including cblC defect:
CYSTADANE (betaine anhydrous for oral solution) is indicated in children and adults for the treatment of homocystinuria to decrease high homocysteine blood levels. Homocystinuria is a rare genetic disorder in which there is an abnormal accumulation of the amino acid homocysteine in the blood and urine. The following are considered to be homocystinuria disorders: