What is homocystinuria and how does it affect the body. How is homocystinuria diagnosed in newborns. What are the potential complications of untreated homocystinuria. How is homocystinuria treated through diet and medication. What is the genetic inheritance pattern of homocystinuria.

Understanding Homocystinuria: A Rare Metabolic Disorder

Homocystinuria (HCU) is an uncommon inherited condition that affects the body’s ability to process certain amino acids. Specifically, individuals with HCU cannot fully break down methionine, an essential amino acid found in many protein-rich foods. This metabolic deficiency leads to a harmful accumulation of methionine and homocysteine in the blood and urine.

The normal process of protein metabolism involves breaking down foods like meat and fish into amino acids, which are then used by the body or further broken down for removal. However, in HCU, this process is disrupted, resulting in potentially serious health consequences if left untreated.

Key Facts About Homocystinuria:

• It is a rare genetic disorder
• Affects the breakdown of the amino acid methionine
• Causes elevated levels of homocysteine in blood and urine
• Can lead to various health complications if not treated early
• Requires lifelong management

Diagnosing Homocystinuria: Early Detection is Crucial

Early diagnosis of homocystinuria is vital for preventing serious complications. How is HCU typically diagnosed? The primary method for detecting HCU is through newborn screening. At around 5 days old, babies undergo a newborn blood spot test, which involves collecting a small blood sample from the heel to check for various conditions, including HCU.

If HCU is suspected based on the screening results, further diagnostic tests are conducted to confirm the diagnosis. Early detection allows for prompt initiation of treatment, significantly reducing the risk of severe complications associated with the condition.

Importance of Newborn Screening:

• Allows for early diagnosis before symptoms appear
• Enables timely treatment initiation
• Helps prevent serious health complications
• Improves long-term outcomes for affected individuals

Recognizing the Symptoms of Homocystinuria

While babies born with HCU typically don’t exhibit symptoms in their first year of life, untreated HCU can lead to severe health issues as the child grows older. What are the potential symptoms and complications of untreated homocystinuria?

• Vision problems, particularly severe myopia (short-sightedness)
• Osteoporosis (weak bones)
• Joint and bone problems
• Increased risk of blood clots and strokes
• Potential brain damage and developmental delays

It’s important to note that with early diagnosis and proper treatment, many of these complications can be prevented or minimized. This underscores the critical importance of newborn screening and early intervention for children with HCU.

Treatment Approaches for Homocystinuria

Managing homocystinuria requires a multifaceted approach tailored to each individual’s specific needs. The primary goals of treatment are to reduce homocysteine levels in the body and prevent the development of serious complications. What are the main treatment strategies for HCU?

1. Vitamin B6 (Pyridoxine) Supplementation

Some individuals with HCU respond well to vitamin B6 supplementation. In these cases, taking vitamin B6 can help control homocysteine levels. If effective, this treatment needs to be continued lifelong.

2. Specialized Diet

For those who don’t respond to vitamin B6 alone, a low-protein diet is essential. This diet aims to reduce methionine intake while ensuring adequate nutrition for growth and development. What does a low-protein diet for HCU involve?

• Limiting high-protein foods such as meat, fish, cheese, eggs, pulses, and nuts
• Carefully monitored intake of breast milk or formula for infants
• Use of special low-protein foods and formula milk
• Regular consultation with a metabolic dietitian

The diet must be carefully balanced to provide all necessary nutrients while controlling methionine intake. As children grow, they need to learn how to manage their diet independently, always under the guidance of healthcare professionals.

3. Medication

In addition to dietary management, some individuals may be prescribed betaine, a medication that helps clear excess homocysteine from the body. This treatment is typically introduced in later childhood and needs to be taken regularly as directed by a doctor.

4. Regular Monitoring

Ongoing monitoring through blood tests is crucial to ensure that homocysteine levels remain within an acceptable range. This allows for timely adjustments to the treatment plan if needed.

The Genetic Basis of Homocystinuria

Homocystinuria is an inherited condition, but how exactly is it passed on from parents to children? HCU follows an autosomal recessive inheritance pattern. This means that for a child to develop HCU, they must inherit two copies of the mutated gene – one from each parent.

Parents who carry one copy of the mutated gene typically don’t show any symptoms of the condition. They are known as carriers. When both parents are carriers, what are the chances of their child being affected?

• 25% chance (1 in 4) of the child having HCU
• 50% chance (2 in 4) of the child being a carrier
• 25% chance (1 in 4) of the child not being affected or a carrier

Understanding the genetic basis of HCU is important for family planning and genetic counseling. If there’s a family history of HCU, it’s crucial to inform healthcare providers to ensure appropriate testing and care for any future children.

Living with Homocystinuria: Long-term Management and Outlook

While homocystinuria is a lifelong condition, early diagnosis and proper management can significantly improve outcomes. How can individuals with HCU lead healthy lives?

• Adhering to the prescribed diet and medication regimen
• Regular check-ups with healthcare providers
• Monitoring for potential complications
• Maintaining a healthy lifestyle
• Seeking support from healthcare teams and support groups

With appropriate care, many individuals with HCU can lead fulfilling lives. However, it’s important to recognize that management of the condition is an ongoing process that requires dedication and support from both the affected individual and their caregivers.

Advances in Homocystinuria Research and Treatment

The field of rare genetic disorders, including homocystinuria, is an area of active research. What are some of the recent advances and future directions in HCU research and treatment?

• Improved genetic testing methods for more accurate diagnosis
• Development of new therapeutic approaches, including enzyme replacement therapies
• Research into gene therapy as a potential future treatment
• Studies on long-term outcomes to improve management strategies
• Exploration of personalized medicine approaches for HCU

These ongoing research efforts offer hope for improved treatments and potentially even curative therapies for HCU in the future. However, it’s important to note that much of this research is still in early stages and may take years to translate into clinical practice.

Support and Resources for Individuals with Homocystinuria

Living with a rare condition like homocystinuria can be challenging, but various support systems and resources are available. What kind of support can individuals with HCU and their families access?

• Specialized metabolic clinics and healthcare teams
• Patient advocacy organizations and support groups
• Educational resources on diet management and lifestyle adjustments
• Genetic counseling services
• Access to clinical trials and research studies

These resources can provide valuable information, emotional support, and practical assistance in managing HCU. They also play a crucial role in raising awareness about the condition and advocating for improved care and research funding.

In conclusion, homocystinuria is a complex but manageable condition. With early diagnosis, appropriate treatment, and ongoing support, individuals with HCU can lead healthy and fulfilling lives. Continued research and awareness efforts offer hope for even better outcomes in the future.

Homocystinuria – NHS

Homocystinuria (HCU) is a rare but potentially serious inherited condition.

It means the body can’t process the amino acid methionine. This causes a harmful build-up of substances in the blood and urine.

Normally, our bodies break down protein foods like meat and fish into amino acids, which are the “building blocks” of protein. Any amino acids that aren’t needed are usually broken down and removed from the body.

Babies with HCU are unable to fully break down methionine, causing a build-up of methionine and a chemical called homocysteine. This build-up can be harmful.

Diagnosing homocystinuria

At around 5 days old, babies are offered a newborn blood spot test to check if they have HCU. This involves pricking your baby’s heel to collect drops of blood to test.

If HCU is diagnosed, treatment can be given to reduce the risk of serious complications. Treatment may include trial doses of vitamin B6 (pyridoxine), a special diet and advice.

With early diagnosis and the correct treatment, the majority of children with HCU are able to live healthy lives. However, treatment for HCU must be continued for life.

Babies born with HCU don’t usually have any symptoms in the first year of their life. But severe symptoms can develop later in life without early treatment. These may include:

• vision problems, such as severe short-sightedness (myopia)
• weak bones (osteoporosis)
• bone and joint problems
• a risk of developing blood clots and strokes

Some children with untreated HCU are also at risk of brain damage, and their development might be affected.

Treating homocystinuria

Vitamin B6 (pyridoxine)

In some babies, it’s possible to control the levels of homocysteine with vitamin B6 (pyridoxine). If this works, your child will need to take vitamin B6 supplements for the rest of their life.

Diet

Children diagnosed with HCU that doesn’t respond to vitamin B6 are referred to a specialist metabolic dietitian and given a low-protein diet. This is tailored to reduce the amount of methionine your baby receives.

High-protein foods need to be limited, including:

• meat
• fish
• cheese
• eggs
• pulses
• nuts

Your dietitian will provide detailed advice and guidance, as your baby still needs some of these foods for healthy growth and development.

Breastfeeding and baby milk also need to be monitored and measured, as advised by your dietitian. Special formula milk may be used. The diet will be designed to contain all the vitamins, minerals and other amino acids your baby needs.

As your baby moves on to solid foods, your dietitian can explain which low-protein foods are suitable. Some of these may be available on prescription, including low-protein rusks, milk substitutes and low-protein pasta.

People with HCU may need to follow a modified diet for the rest of their life. As your child gets older, they’ll eventually need to learn how to control their diet and stay in contact with a dietitian for advice and monitoring.

Regular blood tests will also be needed to monitor the amount of homocysteine in their blood.

Medicine

Alongside a low-protein diet, your child may be prescribed a medicine called betaine in later childhood to help clear some of the excess homocysteine.

Medicine for HCU needs to be taken regularly, as directed by your doctor.

How homocystinuria is inherited

The genetic cause (mutation) responsible for HCU is passed on by parents, who usually don’t have any symptoms of the condition.

The way this mutation is passed on is known as autosomal recessive inheritance. This means a baby needs to receive two copies of the mutated gene to develop the condition – one from their mother and one from their father. If the baby only receives one affected gene, they’ll just be a carrier of HCU.

If you’re a carrier of the altered gene and you have a baby with a partner who’s also a carrier, your baby has:

• a 1 in 4 chance of developing the condition
• a 2 in 4 chance of being a carrier of HCU
• a 1 in 4 chance of receiving a pair of normal genes

Although it’s not possible to prevent HCU, it’s important to let your midwife and doctor know if you have a family history of the condition.

Any further children you have can be tested for the condition as soon as possible and given appropriate treatment.

You may also wish to consider genetic counselling for information and advice about genetic conditions.

Information about your child

If your child has HCU, your clinical team will pass information about them on to the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about NCARDRS on GOV.UK.

Page last reviewed: 19 May 2022
Next review due: 19 May 2025

Homocysteine Urine Test

Approved by

Maulik P. Purohit MD, MPH Assistant Medical Director July 25, 2019

The Homocysteine Urine Test measures homocysteine levels in urine. It is used to detect vitamin B deficiency or genetic disorders affecting homocysteine metabolism.

What are the other Names for this Test? (Equivalent Terms)

• Urine Homocysteine Test 

What is Homocysteine Urine Test? (Background Information)

• Homocysteine is an amino acid found in most cells of the body, in trace amounts. It is an intermediate in the conversion of the amino acid methionine into other products, such as cysteine
• The metabolism of methionine through homocysteine involves enzymes that use vitamins B₆ (pyridoxine), B₉ (folate), and B₁₂ (cobalamin). Ample supplies of these B vitamins keep the enzymes functioning and prevent homocysteine buildup
• Normally, homocysteine levels are low, because it is constantly turned into other products. In the case of vitamin B deficiencies or genetic enzyme defects, the metabolism of methionine through homocysteine may slow or stop. This results in elevated homocysteine levels and it accumulates in the body cells
• This may increase the risk of cardiovascular disease, because large amounts of homocysteine can damage the inner endothelial lining of blood vessels, change clotting factor levels, and make platelets more prone to aggregation
• The Homocysteine Urine Test measures homocysteine levels in urine. It is used to detect vitamin B deficiency or genetic disorders affecting homocysteine metabolism. This also provides an indirect assessment of the risk for cardiovascular diseases 

What are the Clinical Indications for performing the Homocysteine Urine Test?

Following are the clinical indications for performing a Homocysteine Urine Test:

• Fatigue
• Pale appearance
• Rapid heart rate
• Trouble breathing
• Chest pain radiating to the jaw
• Tingling in the extremities
• Glaucoma
• Nearsightedness
• Dizziness
• Seizures 

How is the Specimen Collected for Homocysteine Urine Test?

Following is the specimen collection process for Homocysteine Urine Test:

Sample required: Urine

Process: Urination into a sterile container.

Preparation required: Fasting for 2-12 hours may be necessary 

What is the Significance of the Homocysteine Urine Test Result?

The significance of the Homocysteine Urine Test is explained:

• Increased homocysteine urine levels may indicate:
  • Vitamin Bdeficiency
  • Chronic kidney failure
  • Homocystinuria (a genetic disorder)
  • Coronary artery disease (CAD) 

The laboratory test results are NOT to be interpreted as results of a “stand-alone” test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario. 

Additional and Relevant Useful Information:

• In pregnant women, elevated urine homocysteine levels may affect fetal development, especially of the nervous system
• Homocysteine levels lag behind vitamin B12 levels; so treatment for possible vitamin B12 deficiency may be started, even before the results of this test becomes available
• With rare exceptions, vitamin B12 is available only from animal sources. Individuals with vegan diets are at an increased risk for vitamin B12 deficiency, and must supplement their diets with foods containing vitamin B12 

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

Lab Tests Online (2014, April 30). Retrieved August 31, 2014 from http://labtestsonline.org/understanding/analytes/homocysteine/

Martini, F., Nath, J. L., & Bartholomew, E. F. (2012). Fundamentals of anatomy & physiology (9th ed.). San Francisco: Benjamin Cummings.

Schnell, Z. B., Van, L. A., & Kranpitz, T. R. (2003). Davis’s Comprehensive handbook of laboratory and diagnostic tests: With nursing implications. Philadelphia: F.A. Davis.

Get tested for homocysteine ​​- prices in Moscow at INVITRO

Method of determination

ELISA.

Test material
Heparinized plasma

Online check-in

Homocysteine ​​is an amino acid, an intermediate product formed during the metabolism of the amino acid methionine, a risk factor for atherosclerosis.

Synonyms: Total plasma homocysteine; hcy; Plasma Total Homocysteine.

Brief characteristics of the analyte Homocysteine ​​

Homocysteine ​​is a sulfur-containing amino acid, a homologue of the amino acid cysteine, differing by one methylene group. In the body, homocysteine ​​is formed as a result of the metabolism of the essential amino acid methionine, which comes from animal proteins: meat, dairy products (especially cottage cheese), eggs, etc. In blood plasma, homocysteine ​​is predominantly in protein-bound form. Total plasma homocysteine ​​is the total content of free and bound forms. Most of it undergoes reverse methylation with the formation of methionine. Alternatively, it may undergo irreversible conversion to cysteine ​​and glutathione. Vitamins B12, B6, folic acid are involved in the metabolism of homocysteine.

The level of homocysteine ​​in the blood increases with age.

Gender differences are also observed: up to approximately 50 years of age, the content of homocysteine ​​in plasma in men is slightly higher than in women. In case of violations of homocysteine ​​metabolism due to genetic or functional defects of the enzymes involved in the reactions, with a deficiency of essential vitamins, it accumulates inside the cells in an increased amount, enters the extracellular space, and then into the blood plasma. An increased concentration of homocysteine ​​is cytotoxic.

Homocysteine ​​is oxidized in the blood plasma, with the formation of a large number of oxygen-containing radicals that damage the vascular endothelium. As a result of damage to the endothelium, thromboresistance of the vascular wall decreases, platelet aggregation increases, stimulation of proliferative processes in the vascular wall occurs, and thrombovascular pathology develops. People with elevated levels of homocysteine ​​(above 15 µmol/l) have an increased risk of Alzheimer’s disease and senile dementia. With a combination of hyperhomocysteinemia and diabetes mellitus, vascular complications occur more often: peripheral vascular disease, nephropathy, retinopathy, etc. During pregnancy, elevated homocysteine ​​levels can cause complications such as spontaneous abortion (as a result of impaired fetoplacental circulation and intrauterine fetal hypoxia), preeclampsia and eclampsia, venous thromboembolism. A significant increase in the content of total homocysteine ​​is observed in patients with homocystinuria. Homocystinuria is a rare (orphan) genetic disease of the aminoacidopathy group, caused by a metabolic disorder of sulfur-containing amino acids, primarily methionine.

Homocystinuria is characterized by an increase in the concentration of methionine and homocysteine ​​in the blood serum, the appearance of homocystin (not contained in the norm) in tissues and biological fluids, and a decrease in the content of cystine in the blood. There is also an increased renal excretion of methionine, homocysteine, homocystine and a reduced – cystine.

Non-specific symptoms that appear first of all may be expressed by psychomotor retardation, mental retardation, skeletal deformities (valgus setting of the knee joints, kyphoscoliosis, pectus excavatum or keeled deformity of the chest), cardiovascular pathology, frequent fractures (especially in older children) . Pathological changes in the visual analyzer are characteristic: subluxation (luxation) of the lenses, often complicated by secondary glaucoma (often with a malignant course), myopia, atrophy of the optic nerves, cataracts and retinal detachment.

Adolescents and young people may develop thrombosis, which is the main cause of myocardial infarction or stroke with the formation of focal neurological symptoms.

Why determine the level of Homocysteine ​​

The determination of homocysteine ​​in blood plasma is currently used to assess the risk of developing cardiovascular diseases, along with the determination of cholesterol, high and low density lipoproteins, fibrinogen, C-reactive protein by a highly sensitive method. Studies in recent years show that homocysteine ​​is an independent risk factor for cardiovascular disease.

An increase in blood homocysteine ​​by 5 µmol/l leads to an increase in the risk of atherosclerotic vascular disease by 80% in women and by 60% in men.

Reducing plasma homocysteine ​​may reduce the risk of cardiovascular complications. With an elevated level of homocysteine, it is recommended to simultaneously investigate the concentration of creatinine, TSH, folic acid, vitamin B12 to establish a possible cause of hyperhomocysteinemia and conduct adequate treatment.

What is the purpose of determining the level of Homocysteine ​​in the blood

Determination of homocysteine ​​in blood plasma is used in the diagnosis of B12 and folate deficiency anemia, some congenital metabolic disorders (including homocystinuria), as well as for the purpose of additional assessment of cardiovascular risks.

What can affect your homocysteine ​​levels? homocysteine ​​levels. The mechanism of action of these factors is due to direct or indirect antagonism with enzymes or cofactors involved in the metabolism of homocysteine. The most common cause of elevated homocysteine ​​levels is folic acid deficiency. A lack of vitamin B12, even with an adequate intake of folic acid, can also lead to accumulation of homocysteine.

Homocysteine ​​

This non-proteinogenic amino acid is an intermediate in the metabolism of the essential amino acid methionine, which occurs in the presence of folic acid, vitamins B12, B6, B2 and magnesium. Large amounts of methionine are found in meat, milk, cheese, fish, white bread, processed and canned foods.

With a deficiency of the above vitamins, the content of homocysteine ​​in the body increases and hyperhomocysteinemia develops. It causes damage to the inner wall of blood vessels. Violation of the integrity of the endothelium causes the formation of blood clots, atherosclerotic plaques.

People with high levels of homocysteine ​​are at greater risk of developing Alzheimer’s disease and dementia. Against the background of diabetes mellitus, a high level of this amino acid threatens with vascular complications.

During pregnancy, an increased amount of homocysteine ​​can provoke fetoplacental circulation disorders. This can lead to miscarriage, implantation defects of the embryo, intrauterine fetal hypoxia, generalized microangiopathy.

Causes of elevated homocysteine ​​levels

An excess of this amino acid in the blood may be associated with a mutation (most often C677T) in the MTHFR gene. It encodes a protein of the same name, which plays the role of an enzyme in the biosynthesis of homocysteine ​​from methionine.

The cause of hyperhomocysteinemia is also believed to be a lack of folic acid in the body. However, in people with a mutation in the MTHFR gene, its supplementation does not normalize homocysteine ​​levels.

In order to find out the exact cause of the increased concentration of this amino acid, it is necessary to conduct an examination. To determine the genetic prerequisites, you can pass the tests “Folate cycle”, “Impaired hemostasis system”, sequencing of the genes CBS, MTHFR, MTR, MTRR, MMADHC and others at the medical genetic center “Genomed”.

We have prepared for you a list of tests that will help you deal with this problem:

Who needs to get tested for homocysteine?

Indications for examination for the level of this amino acid and the presence of mutations in the MTHFR gene are:

• family history of strokes, heart attacks, thrombosis, ischemic heart disease;
• disorders of the blood coagulation system;
• neurological disorders in children;
• preparation for IVF;
• chromosomal abnormalities in the fetus, congenital pathologies of development, complicated pregnancy;
• smoking.

How is homocysteine ​​tested?

Blood or urine may be used for testing. The material for analysis (blood from a vein) is taken on an empty stomach, 10-12 hours before the test, you can not eat or drink.