Glycine N-methyltransferase deficiency (GNMT deficiency) is a very rare condition characterized by persistent and isolated excess levels of methionine in the blood (hypermethioninemia). The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver disease. Methionine may also be increased in urine. However, because elevated levels of methionine in the blood itself is a risk factor for development of neurological signs and symptoms, people with GNMT deficiency can have neurological problems when methionine levels are greater than 800 μmol/L. GNMT deficiency is caused by mutations in the GNMT gene. Inheritance is autosomal recessive. Treatment is not needed in most cases.

Based on the findings in the five diagnosed individuals, characteristics of GNMT deficiency are mild to moderate fluctuating elevations of aminotransferases and lack of clinical symptoms—the only clinical sign present in two individuals (siblings) being mild increase in the size of the liver (hepatomegaly). Presenting symptoms in three individuals were upper respiratory tract infection, failure to thrive and febrile convulsions, respectively. It is unclear whether these symptoms were related to GNMT deficiency.

One of the patients had a normal liver ultrasound and a normal liver biopsy.

Physicians following patients should be aware that besides the liver, GNMT protein is expressed in a number of tissues (prostate, pancreas, kidney, submaxillary glands, intestinal mucosa, and brain). Regular measurements of aminotransferases, liver function (albumin, prothrombin time) and methionine levels may be useful. Yearly assessments of plasma alpha-fetoprotein levels as well as liver ultrasound and neurological examination may also be recommended.