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Homocystinuria

What is Homocystinuria?

Homocystinuria (HCU) is a rare disease characterized by an individual’s inability to process the amino acid methionine, which can cause harmful build-ups in the blood and urine. The food we eat contains proteins, which are made up of building blocks known as amino acids. When we digest our food, the body breaks down the protein using enzymes into these essential amino acid components to be converted into other proteins or removed. If the body is unable to break down one of these amino acids, it would remain in the bloodstream and cause harmful build-ups. In the case of homocystinuria (HCU), the body cannot properly process the amino acid known as methionine, leading to a build-up of methionine and homocysteine in the body. Homocysteine is a product of the conversion of methionine to another amino acid known as cysteine, and when this metabolic process is interrupted it can lead to build-ups of methionine and all of its byproducts. 

Homocystinuria is an inherited disorder caused by a genetic mutation that limits the body’s ability to break down methionine. It is present from birth and is often tested for in newborns. If diagnosed and treated early, individuals with homocystinuria can live healthy lives and are less likely to develop potentially life-threatening complications such as blood clots.

 

 

Synonyms

  • Cystathionine beta-synthase deficiency

Homocystinuria (HCU) is a rare disease characterized by an individual’s inability to process the amino acid methionine, which can cause harmful build-ups in the blood and urine. The food we eat contains proteins, which are made up of building blocks known as amino acids. When we digest our food, the body breaks down the protein using enzymes into these essential amino acid components to be converted into other proteins or removed. If the body is unable to break down one of these amino acids, it would remain in the bloodstream and cause harmful build-ups. In the case of homocystinuria (HCU), the body cannot properly process the amino acid known as methionine, leading to a build-up of methionine and homocysteine in the body. Homocysteine is a product of the conversion of methionine to another amino acid known as cysteine, and when this metabolic process is interrupted it can lead to build-ups of methionine and all of its byproducts. 

Homocystinuria is an inherited disorder caused by a genetic mutation that limits the body’s ability to break down methionine. It is present from birth and is often tested for in newborns. If diagnosed and treated early, individuals with homocystinuria can live healthy lives and are less likely to develop potentially life-threatening complications such as blood clots.

 

Acknowledgement of Homocystinuria has not been added yet.

Homocystinuria is a rare disease with two known forms. The more common form affects an individual’s eyesight and is diagnosed in 1 in 200,000-335,000 people worldwide. The rarer form of HCU affects intellectual development and has only been reported a small number of times in the literature.

There is a geographical impact on homocystinuria prevalence, with instances occurring in 1 in 65,000 children in Ireland, 1 in 17,8000 children in Germany, 1 in 6,400 children in Norway, and 1 in 1,800 children in Qatar. The current estimated prevalence of homocystinuria in the US is 1 in 100,000 people, but research is beginning to show that this rare disease is being underdiagnosed in newborns and may have higher occurrences in later childhood.

 

Name Abbreviation
Cystathionine beta-synthase deficiency CBSD

Homocystinuria (HCU) is a genetic mutation inherited from the parents through the autosomal recessive inheritance pattern. Some common gene inheritance patterns come from the method of inheriting one chromosome from each parent. If a gene is abnormally short, long, or has other mutations that change the DNA code, it will change proteins in the cell that the cell needs to function and will affect the genetic code of the offspring. In autosomal recessive inherited disorders, a mutated gene must be present on both paired chromosomes in order to exhibit a trait in the offspring. This means that both parents need to possess a chromosome with a mutated gene to pass this trait to their children. 

The more common form of homocystinuria is caused by a mutation in the CBS gene, a gene responsible for the production of an enzyme known as cystathionine beta-synthase which breaks down the amino acid homocysteine and converts it to the active molecule cystathionine. This molecule is then used to produce the amino acid methionine for use in the body. Mutations in the CBS gene can prevent homocysteine from being broken down and used properly within the body. This can result in the build-up of potentially toxic by-products in the blood and released into the urine.

Less common causes of homocystinuria are mutations in the genes MTHFR, MTR, MTRR, and MMADHC. These genes also ​​encode enzymes that play a role in converting homocysteine to methionine. Mutations in these genes can lead to more rare forms of homocystinuria as homocysteine builds up in the body. 

 

Since homocystinuria is present from birth, symptoms may develop immediately or often become present within the first year of life. These can include vision problems, severe short-sightedness (myopia), weakened bones (osteoporosis), bone and joint problems, and an elevated risk of blood clots and stroke. Other physical abnormalities that may lead to a diagnosis of homocystinuria include chest deformities, flushed cheeks, high foot arch, knock knees, long limbs, spidery fingers, tall and lean frame. 

There are less common forms of homocystinuria that may cause intellectual disabilities, deficient weight and height gain, seizures, movement difficulties, and a blood disorder known as megaloblastic anemia that occurs when the individual has a low number of red blood cells combined with larger than normal red blood cells. Additionally, a lack of proper treatment for children with homocystinuria can lead to brain damage and developmental problems. 

 

A diagnosis of homocystinuria usually occurs within the first 5 days of life by conducting a newborn blood spot test to check amino acid levels. Symptoms will often develop within the first year of life, often consisting of eyesight difficulty, but certain features may occur later in childhood. Doctors may further examine an individual for homocystinuria if they present a combination of the following symptoms: dislocated lens in the eye, curved spine or scoliosis, deformity of the chest.

To confirm a diagnosis of homocystinuria, genetic testing for known gene mutations causing the rare disease must be confirmed. There are other tests that can indicate that a diagnosis of HCU:

  1. Newborn blood spot test: Conducted within 5 days of birth, a newborn baby’s heel is pricked to collect drops of blood to conduct a panel of tests. 

  2. Amino acid screen of the blood or urine: This tests for elevated levels of methionine and/or homocysteine.

  3. Blood tests: Regular blood tests to monitor amino acid levels and diet influence may be necessary for individuals with HCU.

  4. Liver biopsy: This involves removing a piece of the liver to examine under a microscope or to conduct other tests. This tests whether the enzymes in the liver are functioning and present in sufficient amounts. 

  5. Skeletal x-ray

  6. Skin biopsy with a fibroblast culture

  7. Ophthalmic exam: This determines if HCU has caused the eye lens to become dislocated and if the individual qualifies for a replacement lens. 

Treatments for homocystinuria can begin as early as diagnosed, with some newborns being treated to prevent complications. Most individuals with HCU are prescribed vitamin B6 (pyridoxine) combined with a special diet to control their high levels of homocysteine. This is effective in about half of cases, with the other half also prescribed a combination of vitamins B6, B9, and B12. Limiting protein intake can also be used in combination with vitamins, avoiding high protein foods such as meat, fish, cheese, eggs, beans, and nuts. For newborn babies, a specialty formula is prescribed with only the vitamins, minerals, and amino acids that their body needs and digests. For children and young adults with homocystinuria, betaine (trimethylglycine) may be administered the clear excess homocysteine from the body. Some individuals also require lens replacement surgery to repair or replace the dislocated eye lens and improve vision problems. In advanced or extreme cases of homocystinuria, individuals with blood clots may be treated with blood thinners or other methods to reduce this health risk.

Early detection and treatment of HCU enables the individual to lead a healthy life, but the treatment must continue lifelong. Individuals who do not monitor or treat their high homocysteine levels in the blood are at an increased risk of developing blood clots. These can potentially be life-threatening as they can lead to stroke and other serious medical problems.

 

Tips or Suggestions of Homocystinuria has not been added yet.
A rare HCU patient Created by Zebradots13
Last updated 3 Feb 2013, 09:17 AM

Posted by Zebradots13
3 Feb 2013, 09:17 AM

I'm one of the oldest documented cases of Homocystinuria (HCU) --I'm 45 years old. I have have CBS enzyme deficiency but have no manifestation of the disorder (only detected by blood tests). My older brother (3 yrs older) has the classical symptoms but fortunate for both of us we were also the first documented cases in the 1970s to respond positively to B6. Recently I also have been diagnosed with Familial Mediterranean Fever

Community News Articles
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Seeking volunteers with homocystinuria to join a paid clinical research study. Find out if you’re eligible today.

Publication date: 1 Feb 2023

Community: Homocystinuria

Do you have classical homocystinuria? You could qualify for a new paid clinical study, from home.


Community External News Link
Title Date Link
Retrophin buys up Orphan Technologies, spending $90M on rare disease drug 10/24/2020
Aeglea BioTherapeutics Receives FDA Rare Pediatric Disease Designation For ACN00177 For The Treatment Of Homocystinuria 12/06/2020
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Clinical Trials


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CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.

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After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.

Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.

Visit sanfordresearch.org/CoRDS to enroll.

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I am the mother of a 9 year old boy with homocystinuria. He is not b 6 responsive so we are on the very strict diet of 20 grams of protein a day and lots of medications. Landon is doing very well...
I have Homocystinuria and Familial Mediterranean Fever
Looking for information regarding MTHFR, genetic blood mutation.
Moro no Brasil,tenho um filho com Homocistinuria ,gostaria muito de trocar informaçoes ,com outras familias .
I'm doing medicine in madras medical college.

 

my younger sister is suffering from homocystinuria type 3 for past 8 years.

 

she has hemiparesis of left hand.

 

my aim is to cure and...

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A rare HCU patient

Created by Zebradots13 | Last updated 3 Feb 2013, 09:17 AM


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