Methionine Synthase Deficiency – cblG

Contact our caring team on 0800 652 3181 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Calls are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

Prefer to email? Our email address is contact@metabolicsupport.org.

Methionine Synthase Deficiency- cblG is caused by a problem in the MTR gene. This gene provides instructions for making an enzyme called methionine synthase. Methionine synthase is essential for the synthesis of methionine, which is important for protein synthesis and other critical functions in the body. 

The problem in the MRT gene leads to its limited activity or complete absence of its activity in the body. As a result, the body is unable to process certain amino acids (building blocks of protein) properly.  

Methionine Synthase Deficiency – cblG is an extremely rare condition, and its exact prevalence is unknown. Up to now, 38 cases of this disorder have been reported in the scientific literature.  

Most often, this condition presents within the first 2 years of life. However, the onset of symptoms can vary from feeding difficulties being apparent in the neonatal period to more rarely, psychiatric symptoms or acute changes in brain function occurring in adolescence or adulthood. 

Signs and symptoms of this condition can vary significantly and can include:  

• seizures 
• a disturbance of brain function (encephalopathy) 
• a blood disorder caused by your bone marrow producing red blood cells which are larger than average (macrocytic anaemia) 
• weak muscle tone (hypotonia) 
• pain, weakness, or a partial inability to move the legs or hips 
• delays in reaching developmental milestones 
• small head size (microcephaly) 
• instability when walking 
• tremors 
• failure to grow or gain weight (failure to thrive) 
• learning difficulties 
• repetitive involuntary eye movements (nystagmus) 
• yellowing of the skin and whites of the eyes (jaundice) 
• diarrhoea  

Because of the variation in symptoms this disorder is often misdiagnosed as other conditions including multiple sclerosis. It can therefore take a while to reach a confirmed diagnosis. The discovery of a build-up of homocysteine levels in the blood and urine and a decreased amount of methionine may raise suspicion and warrant more tests to rule out related inherited metabolic disorders. This disorder can be confirmed by genetic testing. 

There is no cure for this disorder at the moment. The treatment is based on intramuscular injections of hydroxycobalamin. In some cases, doctors may recommend additional treatment with folates and betaine. 

With the treatment, the prognosis is generally good as clinical symptoms disappear or improve quicky after the initiation of the treatment.  

Methionine Synthase Deficiency – cblG can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier. 

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have. 

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.  

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have Methionine Synthase Deficiency – cblG. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own or plan future children. 

References are available on request. Please contact us on 0800 652 3181 or by emailing contact@metabolicsupport.org.

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.