Methionine Synthase Reductase Deficiency (Homocystinuria, cbIE type)

What else is it called?

  • Functional methionine synthase deficiency  
  • Methylcobalamin deficiency  
  • Homocystinuria without methylmalonic aciduria  

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What causes it?

Methionine Synthase Reductase deficiency (Homocystinuria, cbIE type) is caused by mutations (change) in the MTRR gene. This causes a deficiency of the enzyme methionine synthase (MS) which is responsible for forming methionine.  

How common is it?

The prevalence of this disorder in unknown. About 30 cases to date have been reported of the cbIE type. 

What are the signs and symptoms?

The disorder comes on mainly in early childhood. Symptoms include:  

  • Megaloblastic anaemia (a condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells) 
  • Developmental delay  
  • Impaired responsiveness  
  • Hypotonia (state of low muscle tone, also known as floppy baby syndrome) 
  • Seizures (also known as epilepsy)  
  • Cerebral atrophy (shrinking of part of the brain) 

In the first few months of life, patients may suffer from: 

  • Vomiting  
  • Poor feeding  
  • Lethargy  

Patients can develop:  

  • homocystinuria (an inherited disorder of metabolism of the amino acid methionine) 
  • hyperhomocysteinemia (a medical condition in which the patient has abnormally high levels of homocysteine in the blood) 
  • (and sometimes) hypermethioninemia (the excess of a particular amino acid in the blood called methionine)

How is it diagnosed?

Diagnosis is done through specialized blood and urine tests. Increased levels of homocysteine in urine and in plasma can lead to a diagnosis. Identifying mutations (changes) in the MTR genes can confirm the diagnosis.  

Prenatal diagnosis is also possible through identifying the elevated levels of homocysteine in the amniotic fluid.  

Can it be treated?

Treatment is done through an intramuscular injection of 1mg hydroxocobalamin daily. The frequency of the injection is then reduced over time to one dose, one to three times a week.   

Treatment of the mother of an affected foetus by using cobalamin during pregnancy has been found to be affective in preventing development of the disease.  

With treatment, symptoms of hypotonia, lethargy and impaired responsiveness improve within 24-48 hours. However, the improvement in psychomotor condition is slow and usually lacking in improvement.  

Do my family need to be tested?

Methionine Synthase Reductase Deficiency (Homocystinuria, cbIE type) is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.  

Carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with Methionine Synthase Reductase Deficiency (Homocystinuria, cbIE type) are carriers.   

The pattern of inheritance in this condition is autosomal recessive. This means:   

When both parents are carriers, the risk to the baby in each pregnancy is  

  • 25% chance (1 in 4) of developing the condition  
  • 50% chance (1 in 2) for the baby to be a carrier of the condition  
  • 25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier  

Relevant Organisations


References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing [Resource Library No: AAP002]. 


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