Genotype and Clinical Characteristics of Methioninemia Patients: A Comprehensive Study in a Single Institution

Backgrounds: Hypermethioninemia is usually discovered incidentally in newborn metabolic disease screening tests (NST) to detect homocystinuria. While most cases are asymptomatic, some may exhibit neurological symptoms. This study aims to describe the clinical characteristics and genotype of Korean patients diagnosed with hypermethioninemia due to MATA1A gene mutation.

Methods: This retrospective study analyzed 13 patients who visited the clinic between Jan. 2012 and Dec. 2022. The study assessed patient data, including clinical outcomes, genetic tests, and laboratory findings related to hypermethioninemia.

Results: All 13 patients, consisting of 12 females and 1 male, exhibited abnormal findings by NST between 2 to 7 days postpartum. The average age of genetic diagnosis was 3.3 months, with the initial average plasma levels of methionine and homocysteine being 186.25 nmol/mL and 10.9 umol/L, respectively. Two patients showed increased plasma homocysteine. Among the 10 mutations observed in the MAT1A gene, the c.746G>A mutation was the most frequent (4/13 patients, 30.8%) followed by the c.1005C>G (2/13 patients, 15.4%). At the last follow-up, plasma methionine was elevated in 50% of the patients (5 out of 10) with an average value of 225.3 nmol/mL. Developmental tests for 9 patients indicated speech delay in 2 patients (c.791G>A, c.1005C>G) and motor delay in 1 patient (c.746G>A). Parental inheritance was confirmed in four children.

Conclusions: In the study, the genetic variant appears to be dominated by the c.746G>A, and the other variants show each individual mutation. Most patients with methioninemia have normal development, but 33.3% have developmental delays. Continued research on the relationship between genotype and clinical symptoms is needed for establishing personalized treatment plans.