Homocystinuria (HO‑mo‑SIS‑tun‑YUR‑ee‑uh) is the term used for several rare genetic disorders (diseases passed down through families) that cause levels of homocysteine to build up in blood and urine. This build-up occurs when the body cannot properly process methionine (meh‑THIGH‑uh‑neen) or homocysteine (HO‑mo‑SIS‑teen)—two very important amino acids. Amino acids are the building blocks that the body uses to make proteins.
The homocystinurias are inherited disorders that are caused by certain genes that are abnormal. In order to have homocystinuria, a person must have inherited an affected gene from both parents.
Homocystinuria caused by cystathionine beta-synthase (CBS) deficiency is also called classical homocystinuria. CBS is an enzyme. Enzymes are proteins that regulate the body’s tissues and organs. Specifically, CBS helps convert an important amino acid—homocysteine—to another amino acid that the body needs. When the body does not produce enough CBS, levels of homocysteine and methionine (also an important amino acid) in the blood increase. The high levels of homocysteine cause harmful symptoms to develop.
CBS deficiency is divided into 2 subgroups:
Homocystinuria caused by CBS deficiency can affect many parts of the body:
Learning problems and developmental delays, such as being slow to sit up, walk, or talk
Problems with the lenses in the eyes, such as lens dislocation or cataracts; nearsightedness (often severe); quivering of the iris (the colored part of the eye)
Tall, thin body with long arms, legs, fingers and toes; curved spine; osteoporosis (brittle or weak bones)
Development of blood clots
Infants with CBS deficiency appear to be normal at birth but, if not treated, will slowly develop symptoms.
All states screen newborns for homocystinuria caused by CBS deficiency:
If someone has a positive newborn screen and/or symptoms that could be signs of homocystinuria caused by CBS deficiency, the doctor will order lab tests. These results may point to a positive diagnosis:
Once the diagnosis has been made, more tests will be done to measure response to vitamin B6. This will help determine what type of CBS deficiency the person has and will lead to a treatment plan. Genetic testing can confirm the diagnosis.
The goal of overall treatment is to prevent or lessen symptoms by reducing the level of homocysteine in the blood. Treatment may include:
Always check with your doctor about what medications and diet are right for you.
Homocystinuria caused by 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is very rare. MTHFR is an enzyme. Enzymes are proteins that regulate the body’s tissues and organs. Specifically, MTHFR helps convert an important amino acid—homocysteine—back to methionine, another important amino acid. When the body does not produce enough MTHFR, blood levels of homocysteine increase and blood levels of methionine decrease. This causes harmful symptoms to develop.
Symptoms of homocystinuria caused by severe MTHFR deficiency can begin in infancy or early childhood. Symptoms are often severe and may include:
Small head size and
underdeveloped brain at birth
Developmental delays, such
as being slow to roll over
Poor muscle tone
Failure to grow and gain
weight as expected
Behaviors that are not
typical for the child’s age
The goal of overall treatment is to lessen symptoms by reducing the level of homocysteine and maintaining a normal level of methionine in the blood. Treatment may include:
Always check with your doctor about what therapies are right for you.
Homocystinuria caused by cobalamin cofactor metabolism (cbl) defects 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, cblE, cblF, cblG, cblJ, and cblX.
By far the most common and best understood type of cbl defects is cblC defect. CblC defect causes two disorders: homocystinuria and methylmalonic acidemia (MMA). MMA causes methylmalonic acid to build 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.
Symptoms of homocystinuria caused by cblC defect can develop for the first time at any age and can vary greatly from person to person. Symptoms may include:
Small size overall; small head and underdeveloped brain; poor muscle tone; failure to grow; failure to nurse; vomiting
Not wanting to nurse or take a bottle; failure to grow and gain weight as expected; poor muscle tone; wandering eye movements; seizures or other brain disorders; vomiting
Toddlers and Young Children
Failure to grow and gain weight as expected; poor head growth; anemia; developmental delay, such as slow to walk or talk; seizures or other brain disorders
Adolescents and Adults
Symptoms related to mental functioning and behavior, such as personality changes, hallucinations (seeing or hearing things that aren’t there), poor memory, and poor performance in school or at work; spinal cord degeneration
Although less is known about other cbl defects that cause homocystinuria, they have many of the same symptoms as cblC defect.
Newborn screening for homocystinuria caused by cblC or cblD defect is done in most, but not all, states. 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 cbl defects, your doctor will order lab tests. These results may point to a positive diagnosis for most types of cbl defects, including cblC defect:
The goal of overall treatment is to prevent or lessen symptoms by reducing the levels of homocysteine and maintaining normal levels of methionine in the blood. Treatment may include:
Always check with your doctor about what therapies are right for you.
If you or your child is diagnosed with homocystinuria, you’ll want to find out as much as you can about the disease. The following educational and advocacy groups provide information about rare genetic disorders, including the different types of homocystinuria. You can explore these groups online.
HCU Network America
The mission of the HCU Network America is to help patients with homocystinuria (HCU) and related disorders manage their disease and to find a cure.
Organic Acidemia Association
The Organic Acidemia Association is a patient advocacy organization that provides support and information for people with inherited metabolic disorders. Homocystinuria caused by several cobalamin defects—cblC, cblD, cblF, cblJ, and cblX—is included as a part of the group’s advocacy for methylmalonic acidemia (MMA).
NORD - National Organization for Rare Disorders
NORD is patient advocacy organization dedicated to helping people with rare diseases. NORD provides information on homocystinuria due to CBS deficiency.
CYSTADANE (betaine anhydrous for oral solution) is indicated 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: