Many rare diseases have limited information. Currently GARD aims to provide the following information for this disease:

• Population Estimate:Fewer than 1,000 people in the U.S. have thisdisease.
• Symptoms:May start to appear at a variety of ages.
• Cause:This disease is caused by a change in the genetic material (DNA).

Can This Disease Be Passed Down From Parent to Child?

Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. This is known as inheritance. Knowing whether other family members have previously had this disease, also known as family health history, can be very important information for your medical team.

There are multiple ways, or patterns, a disease can be inherited depending on the gene(s) involved. Based on GARD's current data, this disease can be inherited in the following pattern(s):

Autosomal Recessive

Autosomal means the gene involved is located on one of the numbered chromosomes. Recessive means that a child must inherit two copies of the mutated gene, one from each biological parent, to be affected by the disease. A carrier is a person who only has one copy of the genetic mutation. A carrier usually doesn't show any symptoms of the disease.

If both biological parents are carriers, there is a 25% their child inherits both copies of the mutated gene and is affected by the disease. Additionally, there is a 50% chance their child inherits only one copy of the mutated gene and is a carrier.

• Muscle disease (myopathy) with a blood exam showing an increase of the CK activity (in 100% of the reported cases)
• Hypotonia
• Developmental delay
• Behavioral disorders
• Very small head (microcephaly)
• Myelination delay
• Strabismus
• Problems with blood coagulation
• Liver disease

Genetic Mutations

S-adenosylhomocysteine hydrolase deficiency is caused by genetic mutations, also known as pathogenic variants. Genetic mutations can be hereditary, when parents pass them down to their children, or they may occur randomly when cells are dividing. Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these.

If you suspect you may have this disease, you may want to start collecting your family health history. Information such as other family members who have had similar symptoms, when their/your symptoms first appeared, or exposures to any potential disease-causing environmental factors should be discussed with your medical team.

Known Genetic Mutations

S-adenosylhomocysteine hydrolase deficiency is caused by genetic mutations in the following known gene(s): AHCY

Given these known genetic mutation(s), you may want to ask your health care team if genetic testing is right for you. Genetic tests are laboratory tests that use samples of blood, saliva, or other tissues to help identify changes in genes, chromosomes, or proteins. Genetic testing can help confirm or rule out a suspected genetic disease, or can provide other useful information to your health care team.

Disruption in Metabolism

S-adenosylhomocysteine hydrolase deficiency is caused by a disruption in a person's metabolism. Metabolism is the series of chemical reactions in our body that turns the food we eat into energy and removes toxins. Hormones and specific proteins, called enzymes, help make the right chemical reactions happen in the right order. However, genetic changes can prevent hormones or enzymes from working properly, which can lead to a disruption in metabolism such as energy not being created for the body or toxins not being removed from the body.

Normal Function

The AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme is involved in a multistep process that breaks down the protein building block (amino acid) methionine. Specifically, S-adenosylhomocysteine hydrolase controls the step that converts the compound S-adenosylhomocysteine to the compounds adenosine and homocysteine. This reaction also plays an important role in regulating the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to other compounds (methylation). Methylation is important in many cellular processes. These include determining whether the instructions in a particular segment of DNA are carried out, regulating reactions involving proteins and lipids, and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters).

Health Conditions Related to Genetic Changes

Hypermethioninemia

More than 10 variants (also known as mutations) in the AHCY gene have been described in people with hypermethioninemia. Most of these variants substitute one amino acid for another amino acid in the S-adenosylhomocysteine hydrolase enzyme, causing it to process methionine less efficiently. Other variants introduce a premature stop signal in the instructions for making the S-adenosylhomocysteine hydrolase enzyme. As a result, a shortened, nonfunctional enzyme is produced. These changes reduce the activity of the S-adenosylhomocysteine hydrolase enzyme, impairing the breakdown of methionine. As a result, methionine builds up in the body, which is known as hypermethioninemia. In some cases, excess methionine can cause intellectual disability or other neurological problems in affected individuals.

Other Names for This Gene

• SAHH
• SAHH_HUMAN

Genomic Location

• A low methionine diet: This can decrease and sometimes even normalize the abnormalities in the blood exams. Patients have to be on a protein restricted diet and supplemented with a methionine-free amino acid mixture.
• Supplementation with phosphatidylcholine and creatine: At this time there is no evidence that this treatment is effective.
• Liver transplantation: Recently, liver transplantation was successfully done in one girl at the age of 40 months, but longer follow-up is needed to know the outcome of the liver transplantation.