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Disease Profile
Homocystinuria due to MTHFR deficiency
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Unknown
Age of onset
Infancy
ICD-10
E72.1
Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.
X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Not applicable
Other names (AKA)
Homocysteinemia due to methylenetetrahydro-folate reductase deficiency; Methylenetetrahydro-folate reductase deficiency; Homocysteinuria due to methylenetetrahydro-folate reductase deficiency;
Categories
Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases
Summary
Homocystinuria due to MTHFR deficiency is a genetic condition that results from poor metabolism of folate (also called vitamin B9), due to a lack of working
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.
Homocystinuria usually does not show symptoms in a newborn baby. If untreated, children show signs and symptoms of severe homocystinuria in infancy.
However, homocystinuria due to MTHFR variants can be milder, presenting in later childhood or in adulthood. Symptoms may include abnormal clotting,
https://rarediseases.info.nih.gov/diseases/10770/homocystinuria
For more information on having two common MTHFR gene variants (specifically, C677T and A1298C) visit our page: MTHFR gene variant
Symptoms
Global developmental delays (46% of cases)
Low muscle tone (35%)
Failure to thrive (17%)
Blood vessel disease (16%) (blood clots)
Small head size (15%)
Other possible symptoms include bone disease (
For information on signs and symptoms reported in association with having two common MTHFR
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
Medical Terms | Other Names |
Learn More:
HPO ID
|
---|---|---|
80%-99% of people have these symptoms | ||
Abnormal |
0012379 | |
Cystathioninemia |
High blood cystathionine levels
|
0003286 |
Gait disturbance |
Abnormal gait
Abnormal walk
Impaired gait
[ more ] |
0001288 |
Homocystinuria |
High urine homocystine levels
|
0002156 |
Hyperhomocystinemia |
Elevated blood homocystine
|
0002160 |
Lower limb muscle weakness |
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs
[ more ] |
0007340 |
30%-79% of people have these symptoms | ||
Abnormality of the periventricular white matter | 0002518 | |
Ataxia | 0001251 | |
Brain |
0410263 | |
Hypomethioninemia |
Decreased plasma methionine
Decreased serum methionine
[ more ] |
0003658 |
Mental deterioration |
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline
[ more ] |
0001268 |
Peripheral neuropathy | 0009830 | |
Psychotic episodes | 0000725 | |
Spastic paraparesis | 0002313 | |
5%-29% of people have these symptoms | ||
Apnea | 0002104 | |
Atrophy of the spinal cord |
Degeneration of the spinal cord
|
0006827 |
Bilateral tonic-clonic seizure |
Grand mal seizures
|
0002069 |
Brain atrophy |
Brain degeneration
Brain wasting
[ more ] |
0012444 |
Deep venous thrombosis |
Blood clot in a deep vein
|
0002625 |
Failure to thrive |
Faltering weight
Weight faltering
[ more ] |
0001508 |
Feeding difficulties in infancy | 0008872 | |
Focal-onset seizure |
Seizure affecting one half of brain
|
0007359 |
Generalized neonatal |
Generalized low muscle tone in neonate
|
0008935 |
Global |
0001263 | |
Headache |
Headaches
|
0002315 |
Hemiparesis |
Weakness of one side of body
|
0001269 |
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] |
0001249 | |
Lethargy | 0001254 | |
Psychotic mentation | 0001345 | |
Specific learning disability | 0001328 | |
Thromboembolic stroke | 0001727 | |
1%-4% of people have these symptoms | ||
0001298 | ||
Generalized myoclonic seizure | 0002123 | |
Generalized non-motor (absence) seizure |
Brief seizures with staring spells
|
0002121 |
Too much cerebrospinal fluid in the brain
|
0000238 | |
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] |
0000252 | |
Involuntary, rapid, rhythmic eye movements
|
0000639 | |
Optic atrophy | 0000648 | |
Stroke | 0001297 | |
Ventriculomegaly | 0002119 | |
Percent of people who have these symptoms is not available through HPO | ||
0000007 | ||
Behavioral abnormality |
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] |
0000708 |
Incoordination |
Difficulties in coordination
Incoordination of limb movements
Limb incoordination
[ more ] |
0002311 |
Muscle weakness |
Muscular weakness
|
0001324 |
Paresthesia |
Pins and needles feeling
Tingling
[ more ] |
0003401 |
Seizure | 0001250 |
Cause
Diagnosis
Making a diagnosis for a genetic or rare disease can often be challenging. 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.
Testing Resources
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment
FDA-Approved Treatments
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
- Betaine(Brand name: Cystadane) Manufactured by Orphan Europe SARL
FDA-approved indication: Treatment of homocystinuria to decrease elevated homocysteine blood levels.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Related diseases
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
|
---|
The differential diagnosis should include other homocysteine remethylation disorders.
Visit the Orphanet disease page for more information.
|
Organizations
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Organizations Supporting this Disease
-
Genetic Metabolic Dietitians International
P.O. Box 1462
Hillsborough, NC 27278
E-mail: [email protected]
Website: https://www.gmdi.org/ -
HCU Network America
623 Creek Lane
Flourtown, PA 19031
Telephone: 630-360-2087
E-mail: [email protected]
Website: https://hcunetworkamerica.org/ -
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org -
National Blood Clot Alliance
8321 Old Courthouse Road
Suite 255
Vienna, VA 22182
Toll-free: 1-877-466-2568 (877-4NO-CLOT)
Telephone: +1-703-935-8845
E-mail: [email protected]
Website: https://www.stoptheclot.org/
Organizations Providing General Support
-
Vascular Cures
274 Redwood Shores Parkway, #717
Redwood City, CA 94065
Telephone: +1-650-368-6022
E-mail: [email protected]
Website: https://vascularcures.org/
Learn more
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
Where to Start
- LabTests Online provides information on testing homocysteine levels in general. Click on LabTests Online to view the information page.
- Genetics Home Reference (GHR) contains information on Homocystinuria due to MTHFR deficiency. This website is maintained by the National Library of Medicine.
In-Depth Information
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Homocystinuria due to MTHFR deficiency. Click on the link to view a sample search on this topic.
References
- Homocystinuria. Genetics Home Reference (GHR). March, 2016; https://ghr.nlm.nih.gov/condition=homocystinuria.
- Munoz T, Patel J, Badilla-Porras R, Kronick J, Mercimek-Mahmutoglu S. Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency. Brain Dev. 2015 Jan; 37(1):168-70. Accessed 9/10/2015.
- MTHFR. Genetics Home Reference (GHR). November, 2014; https://ghr.nlm.nih.gov/gene/MTHFR.
- Physician's Guide to The Homocystinurias. The National Organization of Rare Disorders. https://nordphysicianguides.org/wp-content/uploads/2012/02/Homocystinuria_11_29b.pdf. Accessed 9/10/2015.
- Homocystinuria due to deficiency of N(5,10)-Metylenetetrahydrofolate Reductase Activity. Online Medelian Inheritance of Man (OMIM). 2014; https://www.omim.org/entry/236250.
- Varga EA, Sturm AC, Misita CP & Moll S. Homocysteine and MTHFR Mutations: Relation to Thrombosis and Coronary Artery Disease. Circulation. 2005; 111:e289-e293. https://circ.ahajournals.org/content/111/19/e289.full.
- Rosenson RS & Kang DS. Overview of homocysteine. UpToDate. July 21 2017; https://www.uptodate.com/contents/overview-of-homocysteine.
- Homocysteine. American Academy of Family Physicians. 2006; https://familydoctor.org/online/famdocen/home/articles/249.html. Accessed 5/13/2009.
- Homocystinuria due to deficiency of N(5,10)-Methylenetetrahydrofoloate reductase activity. Online Mendelian Inheritance in Man. 2007; https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=236250.
- Liew SC & Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. January 2015; 58(1):1-10. https://www.ncbi.nlm.nih.gov/pubmed/25449138.
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