Homocystinuria Meanings

According to abbreviationfinder, homocystinuria is a rare, genetically determined metabolic disease that is due to an enzyme deficiency and is characterized by an increased concentration of homocysteine in the blood. As part of an early and consistent therapy, homocystinuria can usually be treated well.

What is homocystinuria?

Homocystinuria is a rare, genetically caused amino acid metabolism disease, which is due to defects in various enzymes involved in methionine metabolism (essential amino acid).

Homocysteine and homocystine are degradation or intermediate products of this metabolic process and are immediately further metabolized in healthy people. Due to the presence of defective enzymes, this is only possible to a limited extent in those affected by homocystinuria, so that the concentration of homocysteine in the blood and homocystine in the urine is increased.

The increased concentration of these amino acids, which are considered toxic, can damage various organ systems. Eye diseases (lens luxation, myopia, glaucoma ), skeletal changes ( osteoporosis, marfanoid long limbs), damage to the central nervous system (mental and physical retardation, spasms, cerebrovascular disorders) and the vascular system (thromboembolism, vascular occlusion) are characteristic secondary diseases of homocystinuria.


Homocystinuria is due to an autosomal recessive genetic defect that results in a deficiency of various enzymes involved in methionine metabolism. Three forms of homocystinuria are distinguished depending on the enzyme and sub-process of the methionine metabolism specifically affected.

In the more common type I homocystinuria, there is a deficiency in the enzyme cystathion beta synthase (CBS), which disrupts the synthesis of cysteine from methionine. As a result, homocysteine ​​builds up in the blood (hyperhomocysteinemia) and homocystine in the urine (homocystinuria).

Type II homocystinuria is characterized by a deficiency in 5,10-methylenetetrahydrofolate reductase (MTHFR), which regulates methionine synthesis from homocysteine. This partial metabolic process is correspondingly disturbed in those affected by type II and, in addition to the enrichment of the serum with homocysteine, can also lead to a methionine deficiency.

Type III homocystinuria is characterized by a lack of cobalamin (coenzyme vitamin B12 ). Cobalamin is also involved in methionine synthesis from homocysteine, so a deficiency can also cause elevated blood homocysteine levels and methionine deficiency.

Symptoms, Ailments & Signs

Homocystinuria can occur in different forms. The symptoms are varied and differ depending on the stage of life. Signs of the disease only appear in particularly rare cases before the age of two. Apart from characteristic laboratory findings, newborns with homocystinuria are unremarkable.

Typically, the homocysteine level in the blood is significantly elevated. This damages the blood vessels, which in the long term can lead to vascular calcification (arteriosclerosis) and the associated embolism and thrombosis. As a result, the life expectancy of those affected is significantly limited. The most noticeable symptom of the metabolic disorder in childhood is a prolapse of the eye lens.

This is often accompanied by short-sightedness. The earlier the first signs of the disease appear, the higher the risk of psychomotor retardation ( intellectual disability ), which is irreversible. Most of those affected have osteoporosis as early as childhood. As a result, the spine flattens and gradually deforms.

The high homocysteine value often leads to tall stature and symptoms that can be similar to Marfan syndrome on the outside. These include the presence of a chicken breast and funnel chest, a displaced eye lens ( lens luxation or lens ectopia), glaucoma ( glaucoma ), retinal detachment and spider fingers (arachnodactyly).

Diagnosis & History

Various laboratory analyzes are used to diagnose homocystinuria. If an elevated homocystine concentration and/or reduced methionine concentration (types II and III) is found in a urine analysis (e.g. cyanide-nitroprusside test), this can indicate homocystinuria.

A blood analysis can be used to determine the homocysteine ​​concentration in the serum and to diagnose hyperhomocysteinemia associated with homocystinuria. The diagnosis is confirmed by cultivating cells from a connective or liver tissue sample, which means that the underlying gene defect can be directly detected.

The course of homocystinuria can vary from person to person in terms of symptoms and complications. With an early diagnosis and an early start of therapy, however, homocystinuria usually has a favorable course and a good prognosis.


Homocystinuria primarily causes severe psychological symptoms that can have an extremely negative impact on the patient’s life and everyday life. In most cases, a strong personality disorder occurs, which is accompanied by behavioral disorders. These disorders can lead to serious complications, especially in children.

As a rule, the patient is affected by social exclusion and withdraws more and more from life. It is not uncommon for this to lead to depressive moods. Furthermore, there are problems with the eyes, so that, for example, a glaucoma or short-sightedness can develop. Various diseases of the vessels also appear much earlier and can thus lead to restricted movement.

The treatment itself, as a rule, does not lead to any special complications and is carried out with the help of medication. This leads to a positive course of the disease relatively quickly. Even after the treatment, in most cases there are no further complaints. Life expectancy is not reduced with early treatment. Mental health problems can be treated by a psychologist.

When should you go to the doctor?

If symptoms such as behavioral disorders, thrombosis or delays in development occur, a doctor must be consulted in any case. Likewise, signs of osteoporosis or arteriosclerosis should be clarified at an early stage. A doctor must determine the cause of the symptoms and, if necessary, initiate treatment. Therefore, the symptoms mentioned should be clarified quickly. People with a genetic defect are particularly susceptible to developing homocystinuria. Those affected should consult their family doctor closely and inform them of any unusual symptoms.

Basically, complaints that persist for more than a few days or increase in intensity over a longer period of time must be clarified. The characteristic signs of homocystinuria usually develop insidiously and are often only recognized when irreversible diseases have already set in. It is all the more important to recognize and treat the early symptoms. People who notice physical or mental changes in themselves or others that may be related to metabolic disorders should speak to their family doctor as soon as possible. Other contacts are specialists in internal medicine or a specialist clinic for hereditary diseases.

Treatment & Therapy

The therapy of homocystinuria depends on the underlying type of disease or enzyme defect and aims to reduce and eliminate the increased concentration of toxic homocysteine. Type I homocystinuria is treated with pyridoxine ( vitamin B6 ) if there is residual activity of the defective enzyme.

The substance increases enzyme activity and lowers the homocysteine ​​concentration in the blood. About 50 percent of those affected by this type respond very well to oral therapy with high doses of vitamin B6. In addition, a low-methionine and high-cystine diet is recommended to support therapy.

If there is residual enzyme activity in type II and III homocystinuria, in which methionine synthesis from homocysteine is disturbed, an attempt is made to limit the impairment with cobalamin preparations ( vitamin B12 ). A methionine-rich diet is indicated for both forms of homocystinuria.

In addition, folic acid, which also has a positive effect on the activity of the defective 5,10-methylenetetrahydrofolate reductase, as well as methionine and betaine are used therapeutically in type II . Anticoagulant drugs ( acetylsalicylic acid ) are used to help prevent vascular diseases such as thrombosis and embolism.

Outlook & Forecast

With early diagnosis and intensive therapy, the prognosis of homocystinuria is usually favorable. The disease cannot be cured because it is a genetic defect. However, as part of the therapy, it is possible to permanently reduce the concentration of homocysteine and methionine, which significantly reduces the likelihood of developmental disorders and complications.

The degree of expression of homocystinuria can be varied. There are forms of the disease that are initially inconspicuous and are otherwise mild. However, even here there is a greater risk of developing arteriosclerosis, thrombosis, embolism, heart attacks and strokes from the age of 20 or 30 years.

However, if the homocysteine concentration is already very high in infancy, there is a great risk of physical and mental development disorders in the child without intensive treatment. A mental handicap can already become evident in the first two years of life. The affected children often also suffer from osteoporosis. Up to 70 percent of untreated children develop eye problems, most notably a prolapse of the lens of the eye. Other consequences for the eyes can be greenerstar, extreme myopia, retinal detachment and blindness can occur. If severe forms of the disease are treated too late or not at all, 30 percent of all patients under the age of 20 develop thrombosis and embolism.


Since homocystinuria is a genetic disease, it cannot be prevented. However, if therapy is started early, the complications of homocystinuria can be prevented or limited. In addition, those affected have the option of having their unborn child tested for homocystinuria as part of prenatal diagnostics (amniotic fluid analysis). Siblings of those affected are also recommended to be tested for homocystinuria.


Depending on the type of enzyme defect that is the cause of the metabolic disorder, a whole range of measures are useful and necessary as part of the follow-up care for homocystinuria. In the case of homohystinuria type I, the patient must follow a vitamin-rich diet in addition to the medical administration of vitamin B6. Vitamin B6 increases the activity of the defective enzyme and consequently leads to a lower concentration of homocysteine in the blood.

The diet must be followed permanently for this effect to be maintained. The same applies to the consumption of foods rich in cystine and low in methionine. In the case of homocystinuria type II, the diet must also be continued in order to achieve long-term effects. In addition, regular follow-up checks apply during aftercare. The doctor must check the activity of the affected enzymes and adjust the therapy if necessary.

Since homocystinuria is not usually a serious illness, medical checks at intervals of three to six months are sufficient. In the case of severe disorders, a specialist should be consulted monthly after the actual therapy has been completed. In addition, attention must be paid to unusual symptoms, since the metabolic disorder can cause other diseases in the long term that need to be treated.

You can do that yourself

Depending on the type of enzyme defect that underlies homocystinuria and which therapy the doctor uses, the patient can do a number of things to alleviate the symptoms.

First of all, a cystine-rich diet is important. The affected person should primarily consume rice, nuts, soybeans and oat products. The active ingredient is also found in watermelons, sunflower seeds and green tea. The doctor will also prescribe vitamin B12 supplements to limit the impairment. The person concerned can support these measures by taking a methionine diet together with a nutritionistCreate a nutrition plan and implement it consistently. Foods high in protein such as eggs or meat should be avoided. Low-protein foods are allowed, including fruit, vegetables and low-protein pasta, bread or flour from specialist shops. This diet should also be supported with various B vitamins and folic acid.

After the disease has subsided, the patient should have further check-ups carried out. Homocystinuria is a lifelong disease that requires regular evaluation in a specialized treatment center. Close monitoring means that problems with the metabolism can be identified and treated at an early stage before complications arise.