Homocystinuria is an inherited disorder that keeps the body from processing the essential amino acid methionine. Amino acids are the building blocks of protein. Methionine occurs naturally in various proteins. It is necessary to ensure growth in infants and maintenance of the body’s nitrogen balance in adults.
The illness usually affects infants during the first few years of life, and the more rare forms of the disorder can lead to failure-to-thrive syndrome. Left untreated, homocystinuria can have serious and sometimes fatal complications.
Numerous variations of homocystinuria exist. They range from common to rare. No specific names exist for these variations of the illness. Instead, they are distinguished by their symptoms. Infants who are affected by the common form of this disorder generally experience mild symptoms. In fact, they may not even have symptoms that require treatment until they are older. However, the less common forms of this disorder have been known to cause more serious developmental problems, including impaired intellectual capability.
Certain genetic mutations present at birth cause this disease. According to the National Institutes of Health (NIH), more than 150 mutations that cause homocystinuria are found in the gene cystathionine-ß-synthase, also known as the CBS gene. The CBS gene holds instructions for making an enzyme that uses vitamin B6 to metabolize the amino acids homocysteine and serine. The mutations prevent the normal functioning of the CBS gene. This results in a buildup of homocysteine and other toxins that damage the nervous system, including the brain, and the vascular system.
In rare instances, the mutations in other genes like MTHFR, MTR, or MTRR cause the disorder. Homocystinuria is an autosomal recessive trait. This means that in order for a child to have the signs or symptoms of this condition, he/she would need to inherit the abnormal genetic information or mutated gene from both parents.
Since homocystinuria is passed down from parents to children, a family history of the disorder places children at a higher risk for developing this condition. The most common form of the disorder affects one in 200,000 to 335,000 people around the world (NIH). The disorder is more common in Ireland, Germany, Norway, and Qatar. Diagnosis rates are lower for the more rare variations.
The symptoms will depend on the type of homocystinuria. Symptoms generally develop during the first years of life. However, some people experience symptoms during adulthood. The most common forms of this disorder may involve the following symptoms:
- dislocation of the lenses in the eyes
- abnormal blood clots
- osteoporosis (weakening of the bones)
- learning disabilities
- developmental problems
- chest deformities (protrusion or caved-in appearance of the breast bone)
- long, spindly arms and legs
Less common variations involve these additional symptoms:
- megaloblastic anemia, an anemia involving larger-than-normal red blood cells
- failure to thrive
- intellectual disabilities
- movement and gait abnormalities
Your doctor may look for certain signs to determine whether you or your child has this condition. An extremely thin or tall child is more likely to have the condition. Additionally, your doctor may search for signs such as chest deformities, curvature of the spine, and dislocated lenses in the eyes. An eye examination can reveal a dislocated lens if your child experiences double or significantly impaired vision.
Your doctor may also order a series of tests to determine if your child is affected. These tests may include:
- an X-ray to look for signs of osteoporsis
- genetic testing to look for one of the genes involved in the disorder
- a liver biopsy and enzyme assay to check enzymatic activity
- an amino acid screen (blood and urine) to check for excess homocysteine
- a skin biopsy (fibroblast culture)
There is no cure for homocystinuria. For about half of the people with this disorder, high doses of vitamin B6 are a successful treatment. If you respond well to this supplementation, it is likely that you will have to use daily vitamin B6 supplements for the rest of your life.
Alternatively, if you don’t experience positive results from this therapy, your doctor may recommend eating a diet low in foods containing the amino acid methionine. People diagnosed at an early stage have shown positive responses after switching to this diet.
Your doctor may also recommend taking betaine (Cystadane). Betaine is a nutrient that works to remove homocysteine from the blood. Taking a folic acid supplement and adding cysteine (an amino acid) to the diet are helpful.
There is currently no cure available for this disorder. However, around half of diagnosed patients show improvement from vitamin B6 supplements. Infants or children who are diagnosed at an early age may experience positive results from a low-methionine diet. It is believed that this diet helps to prevent some types of mental disabilities and further complications.
Even with treatment, you may experience serious complications. You may be at risk for blood clots if you have consistently high homocysteine levels. Blood clots can cause serious and possibly fatal complications such as stroke or heart attack. Another complication is learning disabilities. These can be prevented if homocystinuria is diagnosed and treated at an early age. Dislocated lenses can seriously affect vision. People should opt for lens replacement surgery to treat or prevent vision problems.
This disorder occurs as a result of genetic mutations. This can make it challenging to prevent. You should consider genetic counseling if a history of this ailment runs in your family. Prospective parents can use this method to analyze the risks of having a child who inherits the disorder. Requesting an intrauterine diagnosis of the disorder is another possible prevention method. This requires testing a culture of amniotic cells or villi for the presence of the genetic mutation.