Explore
Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins ( amino acids) properly. There are multiple forms of homocystinuria, which are distinguished by their signs and symptoms and genetic cause.
What is Homocystinuria and what causes it?
Infants appear to be normal and early symptoms, if any are present, are vague. Signs and symptoms of homocystinuria that may be seen include the following: A family history of homocystinuria. Flush across the cheeks. Musculoskeletal. Tall, thin build resembling Marfanoid habitus.
What are the signs and symptoms of infant homocystinuria?
Some affected individuals also have developmental delay and learning problems. Less common forms of homocystinuria can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called megaloblastic anemia.
What are the long term effects of homocystinuria?
Specific symptoms of homocystinuria due to CBS deficiency are treated as appropriate. For example, dislocation of the lenses of the eyes (ectopia lentis) or certain skeletal malformations may be treated surgically.
How are the symptoms of homocystinuria treated in CBS deficiency?
What are the symptoms associated with homocystinuria?
What Are the Signs and Symptoms of Homocystinuria?dislocation of the lenses in the eyes.nearsightedness.abnormal blood clots.osteoporosis, or weakening of the bones.learning disabilities.developmental problems.chest deformities, such as a protrusion or a caved-in appearance of the breastbone.long, spindly arms and legs.More items...
Where do the homocystinuria symptoms mostly affect the body?
High levels of both amino acids build up throughout the body, which can be toxic and damage the nervous system. Damage might occur in the brain, as well as in the vessels carrying blood and lymph around the body. The signs and symptoms of homocystinuria become clear in the first year of life.
What happens if homocystinuria is left untreated?
Babies look healthy and normal at birth. If untreated, homocystinuria can cause growth and learning delays. It can also affect the eyes, bones, heart, and blood vessels. develop severe nearsightedness after age one.
How serious is homocystinuria?
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.
What age does homocystinuria present?
Babies with homocystinuria (HCY) are usually healthy at birth. Early screening and treatment can often prevent the signs and symptoms of HCY. If children are not treated, signs of HCY usually begin between ages one and three. The signs and symptoms are highly variable among individuals with HCY.
What foods cause high homocysteine levels?
Elevated homocysteine levels in the bloodstream have been linked with a wide range of health problems. A high-protein diet, especially one that includes red meat and dairy products, can increase blood levels of homocysteine.
What kind of doctor treats homocystinuria?
Patients with inborn errors of metabolism such as homocystinuria are treated first by family physicians and paediatricians. Without a high index of suspicion, physicians can easily overlook a diagnosis of homocystinuria.
What is the screening test for homocystinuria?
The analysis of methionine levels by tandem mass spectrometry (MS/MS) allows the newborn screening for homocystinuria, but false-positive results can be frequently obtained and lead to the unwanted identification of methionine adenosyl transferase (MAT I/III) deficiency.
Is there a cure for homocystinuria?
There is no cure for homocystinuria. About half of people with the disease respond to vitamin B6 (also known as pyridoxine). Those who do respond will need to take vitamin B6, B9 (folate), and B12 supplements for the rest of their lives. Those who do not respond to supplements will need to eat a low-methionine diet.
What are some causes of homocystinuria in humans?
Mutations in the CBS gene cause the most common form of homocystinuria. The CBS gene provides instructions for producing an enzyme called cystathionine beta-synthase. This enzyme acts in a chemical pathway and is responsible for converting the amino acid homocysteine to a molecule called cystathionine.
What deficiency causes homocystinuria?
Classic homocystinuria is caused by deficiency of cystathionine β-synthase (CBS), a pyridoxine (vitamin B6)-dependent enzyme.
Does high homocysteine levels cause anxiety?
Researchers have also reported that increased homocysteine levels elevate the anxiety effects by direct neurotoxic effects (Bisschops et al., 2004; Kruman et al., 2000; Sachdev, 2004), reducing the synthesis of neurotransmitters due to decreased and nonrecycling of s-adenosyl methionine (Bottiglieri et al., 1992, 2000) ...
Which vitamin deficiency causes homocystinuria?
Classic homocystinuria is caused by deficiency of cystathionine β-synthase (CBS), a pyridoxine (vitamin B6)-dependent enzyme.
What kind of disorder is homocystinuria?
Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. Amino acids are the building blocks of life. Pectus excavatum is a condition in which the breast bone (sternum) appears sunken and the chest concave. It is sometimes called funnel chest.
How many types of homocystinuria are there?
Classical Homocystinuria is divided into two types; Vitamin B6 responsive and Vitamin B6 non-responsive. This will be discussed more later. The second route of Homocysteine metabolism is the Remethylation Pathway that depends on Folate, a B vitamin. This pathway converts Homocysteine back to Methionine.
Does high homocysteine levels cause anxiety?
Researchers have also reported that increased homocysteine levels elevate the anxiety effects by direct neurotoxic effects (Bisschops et al., 2004; Kruman et al., 2000; Sachdev, 2004), reducing the synthesis of neurotransmitters due to decreased and nonrecycling of s-adenosyl methionine (Bottiglieri et al., 1992, 2000) ...
How to tell if a child has homocystinuria?
Clear signs that may lead a doctor to test for homocystinuria include a child being extremely thin and too tall for their age or not growing as expected. Additionally, the doctor will look for signs of chest deformity, spinal curvature, and dislocated eye lenses.
What are the complications of homocystinuria?
Complications. The most serious complication of homocystinuria is blood clots, which can be life threatening and increase the risk of stroke. Cognitive disability is also possible, but early diagnosis and successful treatment can reduce the risk. Dislocated lenses of the eyes can damage vision.
What is the genetic disorder in which the body cannot break down a particular amino acid?
Homocystinuria is a genetic disorder in which the body cannot break down a particular amino acid.
What are the symptoms of a symtom?
Symptoms that are less common include: 1 megaloblastic anemia, which is a disorder in which the number of red blood cells is lower than normal, and the blood cells are unusually large 2 infants not growing or gaining weight at the expected rate 3 movement and gait problems 4 seizures
How many babies develop homocystinuria?
Homocystinuria develops in about 1 out of every 200,000 to 300,000 babies in the U.S.
How long does it take to get a diagnosis for homocystinuria?
However, screening does not detect all forms of homocystinuria. A person with the condition may, therefore, not receive a diagnosis for up to 5 years following birth.
What tests can be done to confirm homocystinuria?
Eye exams may reveal vision problems, while X-rays may show signs of weak bones. Genetic testing, amino acid screening, liver biopsies, and liver enzyme tests can also help a doctor confirm a diagnosis of homocystinuria.
How do you know if you have homocystinuria?
[1] [2] [3] Other people with homocystinuria may not have any symptoms until adulthood. The most common symptom seen in adults with homocystinuria is an abnormal blood clot. [3]#N#Other symptoms of untreated homocystinuria can include:#N#Eye:#N#• Dislocation of the lens of the eye#N#• Nearsightedness#N#Skeletal:#N#• Caved-in chest (pectus excavatum)#N#• Curvature of the spine ( scoliosis)#N#• Long, thin bones#N#• Osteoporosis (weak, brittle bones)#N#Central nervous system :#N#• Learning and intellectual disabilities#N#• Psychiatric problems#N#Blood and heart:#N#• Cardiovascular disease#N#• Abnormal blood clots
How many mutations do you have in homocystinuria?
People with homocystinuria inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected).
What genes cause homocystinuria?
Homocystinuria can affect the eyes, skeleton, central nervous system and the blood clotting system. Mutations in the MTHFR, MTR, MTRR and MMADHC genes can cause homocystinuria . All these forms of homocystinuria are inherited in an autosomal recessive manner. [1] . Treatment and long-term outlook varies depending upon the cause of the disorder.
What is the name of the disorder where the body cannot process amino acids?
Homocystinuria refers to a group of inherited disorders in which the body is unable to process certain building blocks of proteins ( amino acids) properly. This leads to increased amounts of homocysteine and other amnio acids in the blood and urine. The most common type of genetic homocystinuria, called CBS deficiency, ...
How to treat homocysteine?
Lowering the level of homocysteine in the blood, either with diet or supplements or both, can prevent symptoms. With treatment, people with the most severe form of homocystinuria can have normal growth and development. Some may still have eye problems or blood clots and should be monitored. [2] Blood clots can be serious and cause organ damage.
What is the most common type of genetic homocystinuria?
The most common type of genetic homocystinuria, called CBS deficiency, is caused by the lack of an enzyme known as cystathionine beta-synthase (CBS). Most states in the United States test for homocystinuria due to CBS de ficiency at birth by newborn screening . Other types are less common, and are caused by different missing or non-working enzymes. ...
Can you test for homocystinuria at birth?
Most states in the US test for homocystinuria due to CBS deficiency at birth by newborn screening. A baby that has a positive newborn screening test needs to have additional blood testing to look for high levels of homocysteine and methionine in the blood. Genetic testing can also be helpful for diagnosis. [1] [2]
When does homocystinuria develop?
The signs and symptoms of homocystinuria typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.
What is the most common form of homocystinuria?
The most common form of homocystinuria is characterized by nearsightedness ( myopia ), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture ( osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.
What genes cause homocystinuria?
Mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria. Mutations in the CBS gene cause the most common form of homocystinuria. The CBS gene provides instructions for producing an enzyme called cystathionine beta-synthase. This enzyme acts in a chemical pathway and is responsible for converting the amino acid homocysteine ...
How many people have homocystinuria?
The most common form of homocystinuria affects at least 1 in 200,000 to 335,000 people worldwide. The disorder appears to be more common in some countries, such as Ireland (1 in 65,000), Germany (1 in 17,800), Norway (1 in 6,400), and Qatar (1 in 1,800). The rarer forms of homocystinuria each have a small number of cases reported in ...
Do people with a mutated copy of the CBS gene have homocystinuria?
Although people who carry one mutat ed copy and one normal copy of the C BS gene do not have homocystinuria, they are more likely than people without a CBS mutation to have shortages (deficiencies) of vitamin B12 and folic acid.
Can homocystinuria be caused by mutations?
Rarely, homocystinuria can be caused by mutations in several other genes. The enzymes made by the MTHFR, MTR, MTRR, and MMADHC genes play roles in converting homocysteine to methionine. Mutations in any of these genes prevent the enzymes from functioning properly, which leads to a buildup of homocysteine in the body. Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.
When are babies tested for homocystinuria?
Babies in the United States and many other countries are screened for homocystinuria (and other conditions) shortly after birth. It’s part of a blood test known as the newborn screen.
What Are the Symptoms?
Babies born with homocystinuria look perfectly fine. Signs and symptoms start to show up within the first few years of life.
What supplements lower homocysteine levels?
Betaine and folic acid. These supplements can lower dangerously high homocysteine levels. Children who don’t get better with vitamin B6 often respond well to betaine.
What happens if you don't break down HCY?
If left untreated, this acid and another called homocysteine build up in your bloodstream and can cause serious problems.
What is HCY in food?
Homocystinuria (HCY) is a rare condition that interferes with your body’s ability to break down a protein from the food you eat.
What are the symptoms of homocystinuria?
If untreated, these children eventually develop mental retardation, ectopia lentis, a marfanoid appearance including arachnodactyly, osteoporosis, other skeletal deformities and thromboembolism. Symptoms of the most severe form of homocystinuria will start in infancy or early childhood.
When does homocystinuria develop?
The signs and symptoms of homocystinuria typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood. Homocystinuria symptoms may occur as mildly delayed development or failure to thrive.
What is the most common gene associated with homocystinuria?
The most common gene associated with homocystinuria is the CBS (cystathionine beta-synthase) gene that causes a lack of the enzyme, cystathionine beta-synthase. Rarer causes of homocystinuria include mutations in the MTHFR, MTR, MTRR and MMADHC genes 18).
What is the name of the disorder in which the body is unable to process the amino acid methionine properly?
Homocystinuria is an inherited disorder in which the body is unable to process the amino acid methionine properly. Methionine from ingested protein is normally converted to homocysteine. In classical homocystinuria due to cystathionine beta-synthase (CBS) deficiency, homocysteine cannot be converted to cystathionine.
Why do we test for homocystinuria?
Most states in the US test for homocystinuria due to CBS deficiency at birth by newborn screening. A baby that has a positive newborn screening test needs to have additional blood testing to look for high levels of homocysteine and methionine in the blood. Genetic testing can also be helpful for diagnosis 22).
How is homocystinuria inherited?
Homocystinuria is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
Why is cysteine low in homocystinuria?
Cysteine is an amino acid that is often low in individuals with homocystinuria due to CBS deficiency. When methionine is broken down (metabolized) it produces cystine. Since individuals with homocystinuria cannot properly breakdown methionine, this may cause low levels of cysteine in some individuals.
Why does MTHFR cause homocystinuria?
Listen. Homocystinuria due to MTHFR deficiency is caused by mutations in the MTHFR gene. This gene tells the body how to make an enzyme, also called MTHFR. MTHFR is important for a chemical reaction in the body involving forms of the vitamin folate. Mutations in the MTHFR gene result in an enzyme that doesn't work like it should, ...
How to make a diagnosis for a genetic disorder?
Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.
Is homocystinuria inherited?
Homocystinuria due to MTHFR deficiency is inherited in an autosomal recessive fashion, which means that both copies of the gene in each cell have mutations in the MTHFR gene. [1]
Can homocystinuria be mild?
However, homocystinuria due to MTHFR variants can be milder, presenting in later childhood or in adulthood. Symptoms may include abnormal clotting, developmental delay, seizures, intellectual disability , and microcephaly. [1] Severe homocystinuria can also be caused by gene variants in other genes besides MTHFR. For more information about other causes of homocystinuria, see the GARD page:
Can a newborn have homocystinuria?
Homocystinuria usually does not show symptoms in a newborn baby. If untreated, children show signs and symptoms of severe homocystinuria in infancy. Newborn screening in most states includes a screening test for homocystinuria so that newborn infants can be treated early in their lives.
Can homocystinuria cause a decrease in enzymes?
Very common gene variants (C677T and A1298C) can cause some decrease in enzyme function. People with homocystinuria due to MTHFR deficiency tend to have two rare variants or sometimes a rare variant and a common variant. Very rarely people inherit a combination of three or four common variants from their parents (for example two C677T variants and two A1298C variants) and may also develop very high levels of homocystine in their body.
How to tell if you have homocystinuria?
Signs and symptoms of homocystinuria that may be seen include the following: 1 A family history of homocystinuria 2 Flush across the cheeks 3 Musculoskeletal#N#Tall, thin build resembling Marfanoid habitus#N#Long limbs ( dolichostenomelia)#N#High-arched feet ( pes cavus)#N#Knock knees ( genu valgum)#N#Pectus excavatum and Pectus carinatum 4 Intellectual disability 5 Seizures 6 Psychiatric disease 7 Eye anomalies:#N#Ectopia lentis – in contrast to Marfan syndrome which features upward ectopia lentis, downward dislocation is the typical finding of homocystinuria or subluxation of lens#N#Myopia ( nearsightedness)#N#Glaucoma#N#Optic atrophy#N#Retinal detachment#N#Cataracts 8 Vascular disease#N#Homocysteine binds to the endothelium of the blood vessels and activate signaling pathways leading to the release of pro-inflammatory molecules. This may cause the following :#N#Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries#N#Intravascular thrombosis
What is the best treatment for homocystinuria?
No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B 6 (also known as pyridoxine ). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B 6 for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine ), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress ). Riboflavin, a cofactor for the MTHFR enzyme pathway and multiple glutathione-related pathways, may also be used.
How to reduce homocysteine levels?
Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys). The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.
What is the name of the condition where the thiol amino acid homocysteine is excreted?
Diagnosis. The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma ). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency.
What is the name of the metabolic disorder in which the amino acid homocysteine is found in the blood?
Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.
How to diagnose CBS deficiency?
CBS deficiency may be diagnosed by routine metabolic biochemistry. Genetic testing may be used to screen for known SNPs ( mutations ). In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration. Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.
What is the effect of homocysteine on the endothelium?
Homocysteine binds to the endothelium of the blood vessels and activate signaling pathways leading to the release of pro-inflammatory molecules. This may cause the following : Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries. Intravascular thrombosis.
How to treat homocystinuria?
Although there is no definite cure for Homocystinuria, its symptoms can be relieved to a great extent by Vitamin B6 therapy in about half of all sufferers. Around half of all individuals with this condition can be effectively treated with administration of high doses of vitamin B6 on a regular basis. Patients who respond favorably to this treatment may not require any further treatment. However, they may need to stick to a special diet that is low in protein, methionine and some other amino acids. A low-methionine diet helps reduce the rate of Homocysteine accumulation in the body.
How many people have homocystinuria?
Homocystinuria is a rare disorder that has an incidence of approximately 1 in 344,000 people in the world population. Read and know all about the causes, symptoms, diagnosis and cure of this syndrome.
What is the best medicine for a patient with a high homocysteine level?
A medication known as Trimethylglycine (also referred to as Betaine) is the preferred choice of medicine for most patients. Betaine transforms Homocysteine into Methionine. This reduces the accumulation rate of Homocysteine to a greater extent and allows Methionine to be integrated into the protein reserves of the body.
What happens if you have high homocysteine levels?
Patients suffering from constant elevation in Homocysteine levels in the bloodstream are at high risk of developing blood clots. Development of clots can result in dangerous medical problems and reduce lifespan.
Why do we need to follow a low methionine diet?
If the diagnosis is conducted while a patient is still young, making him or her quickly follow a low-methionine diet can prevent some of the major complications of the disease such as mental retardation . It is for this reason that some states screen all newborns for Homocystinuria.
What to do if you have a family history of homocystinuria?
If you or any family member is displaying symptoms of this condition, immediately get in touch with your health care provider . This is more important for people having a family history of this disease. Medial consultation is also necessary if you are planning to have children and have a family history of Homocystinuria.
Who should supervise homocystinuria?
Both diet and medications need to be supervised properly by a physician experienced in treating Homocystinuria.
