Research status on hypermethioninemia / 国际儿科学杂志

Hypermetioninemia is a group of rare diseases defined by plasma methionine elevation. The causes of hypermethioninemia include genetic and non-genetic factors. Affecting the transmethylation process in the metabolic pathway between methionine and homocysteine is the common inherited methylation disorders. Most patients had completely asymptomatic and only biochemical abnormalities,others with clinical symptoms were also non-specific, such as mental retardation, cognitive impairment, moderate hepatomegaly, dystonia, Marfans syndrome type,osteoporosis,and cardiovascular disease,and etc. A low methionine diet treatment is rec-ommended,the importance of neonatal screening is emphasized and the birth defects can be reduced through pre-natal diagnosis,but the necessity remains controversial. The long-term prognosis of this disorders is unknown,the plasma of methionine should be measured at regular intervals,and the individualized follow-up is very important.

Hypermethioninemia caused by deficient activity of methionine adenosyltransferase / 临床儿科杂志

Objective To investigate the clinical and molecular genetic characteristics of hypermethioninemia caused by methionine adenosyltransferase deficiency. Methods The clinical data and related gene analysis of hypermethioninemia caused by methionine adenosyltransferase deficiency in 3 children were retrospectively analyzed. The core pedigree analysis was carried out. Results Three children (2 boys and 1 girl) aged from 5 months to 3 years, were from 3 unrelated families. All of them had no family history. One case was found in neonatal screening. One case was onset with pathological jaundice at 1 month old. Another case was found due to tremor and growth retardation at 2 years old. Blood amino acid ester acyl carnitine spectrum analysis showed that all of them had significantly elevated levels of methionine at 134.50-790.67 μmol/L. All children had MAT1A mutation in methionine adenosyltransferase gene. One case was heterozygous mutations with third exon c.274T>C and seventh exon c.895C>T mutation; one case had sixth exon c.757G>A homozygous mutation; and another case had seventh exon c.791G>A homozygous mutation. The core pedigree analysis showed that the mutations were from theirs parents respectively. Conclusions For children with neurologic impairment, methionine metabolic disorders should be considered. Blood amino acids and gene analysis are important methods for confirmation of the diagnosis. Neonatal screening is an effective way to detect this disease.

Spectrum of patients with hypermethioninemia based on neonatal screening tests over 14 years / 소아과

PURPOSE: The neonatal screening test for homocystinuria primarily measures methionine by using a dried blood specimen. We investigated the incidence and clinical manifestations of homocystinuria, isolated hypermethioninemia, and transient hypermethioninemia among patients with hypermethioninemia on a neonatal screening test. METHODS: We performed a retrospective study of 58 patients transferred to Shoonchunhyang Hospital because of hypermethioninemia on a neonatal screening test between January 1996 and August 2009. We analyzed the level of amino acid from plasma and urine, as well as blood homocysteine. RESULTS: Almost half of the 58 patients were identified as normal. Whereas only 3 (5.1%) patients were identified as having homocystinuria, about 20.7% (12 cases) of the patients had isolated hypermethioninemia. The ages of these two groups at initial detection of hypermethioninemia on plasma amino acid analysis were 50.0+/-22.5 days and 34.9+/-13.5 days, respectively. Both groups were put on diets, and they showed a normal developmental course as a result of early diagnosis and treatment. CONCLUSION: Hypermethioninemia without homocystinuria, referred to as isolated hypermethioninemia, was also detected. Thus, the impact of hypermethioninemia on a neonatal screening test should be carefully evaluated through analysis of amino acid levels from blood and urine, and we need to detect and treat an early stage of isolated hypermethioninemia as well as homocystinuria.

Two Cases of Isolated Hypermethioninemia Found by Neonatal Mass Metabolic Screening Tests / 대한임상병리학회지

The neonatal screening test for homocystinuria has mostly measured methionine by use of dried blood specimen. Isolated hypermethioninemia, clinically benign metabolic disorder associated with the deficiency of methionine adenosyl transferase in liver, is discovered in neonatal mass screening tests for homocystinuria. We diagnosed two cases of isolated hypermethioninemia using the amino acid analysis and the liver function tests for newborns with increased methionine level in the Guthrie screening test for homocystinuria. For the first time in Korea, we report two cases of patients with isolated hypermethioninemia with a brief review of literatures.