Methionine adenosyltransferase deficiency

The disease is considered benign in many cases and most patients only have isolated hypermethioninemia. However, about 50% of patients with mutations in the MAT1A gene have developed neurological symptoms later in life, so it cannot be considered to be a benign genetic disorder for all patients. Symptoms that have been described include:

• Problems with psychomotor development or intelligence
• Tremor
• Abnormal muscle contractions,
• Lack of control involving range of movement,
• Severe headaches,
• Abnormal eye movements (nystagmus),
• Impaired ability to make rapid, alternating movements (dysdiadochokinesis),
• Increased tendon reflexes,
• Language difficulties and learning disabilities.

Neurological abnormalities are more common when methionine levels in the blood are above 800 μmol/L and rare in people with lower levels. Brain images may show some changes, such as inflammation and demyelination, especially in patients with neurological problems.

Hypermethioninemia can also be associated with an unusual breath odor likely due to formation of a substance known as dimethylsulfide that results from the problem with the enzyme deficiency.

Liver function tests in patients have been normal so far.

Methionine adenosyltransferase deficiency is the most common cause of persistent isolated hypermethioninemia and should be suspected in people with unexplained hypermethioninemia. Also, when a patient has unexplained neurological signs and symptoms, disorders of methylation should be investigated at least by analysis of plasma amino acids.