Analysis Of Clinical Phenotype And Genotype Of A Child With Hypermethioninemia And Literature Review

Objective In this study,we retrospectively analyzed a case of with only elevated plasma methionine but not with obvious clinical symptoms,which was found in neonatal screening.We summarized the clinical characteristics,diagnosis and treatment of this disease,and explored how to interpretabnormal neonatal screening and genereport with de novo mutation.This would be helpful to be make correct treatment and genetic guidance.Methods 1.subjects: A childwas admitted to the Affiliated Hospital of Qingdao University because of hypermethioninemia.2.methods:(1)The clinical data,laboratory examinations and blood and urine metabolic screening results of the proband were analyzed retrospectively.(2)Summarizing the characteristics of the disease,searching the literature with the key words of typical abnormal amino acid metabolism index,and comparing the detected diseases with the clinical manifestations of the child.3)With the consent of the Medical Ethics Committee of the hospital,communicate and sign the informed consent form with the family members,collect the peripheral blood of the proband and his family members,and directly sequence the coding regions of the related gene exons by sequencing technology,search for suspicious pathogenic genes,and verify the pathogenic genes of other members;Results A 2-month-old girl was found to have elevated plasma methionine during neonatal screening.No clinical symptoms were found,and her growth and development were normal until the time of consultation.Physical examination showed normal mental response,no special disease facial features,no enlargement of liver and spleen.The liver function was mild elevated,and methionine was also slight increased using tandem mass spectrometry.Due to the lack of clinical specificity of the children,we selected the most suitable gene sequencing + MLPA technology to detect the related amino acid metabolism disorder genes,and finally confirmed the existence of a new missense mutation c.315C>A in the MAT1 A gene.Parental verification results that her father carries the same MAT1 A gene missense mutation c.315C>A,meanwhile his methionine was normal which detected by blood tandem mass spectrometry.By reviewing the literature,we learned about a group of diseases named after “hypermethionemia”,which are divided into genetic and non-genetic factors.In the genetic factors,the abnormal methionine metabolic pathway leads to the highest in crease in methionine,which includes four key enzymes: methionine adenosyltrans ferase MAT?and?deficiency,glycine N-methyltrasferase deficiency,s-adenosyl homocysteine hydrolase deficiency,and cystathionine ?-synthase deficiency.Non-genetic factors are more common in patients with liver disease,premature infants/low birth weight infants,methionine-rich diets and other temporary methionine elev ations.In consideration ofthe clinical and biochemical characteristics of different ty pes of this disease,the characteristics of this case and his family history,we hold the opinion thatthis mutation might be a disease-causing mutation with weak path ogenicity.So that explains why this case had transitionalhypermethionemia,and the hypermethionemia could be corrected quickly.Tracking the case's next generation will be helpful to verify the pathogenicity of de novo mutations.After a clear diag nosis,appropriate genetic guidance was given to the child and his or her family.Conclusions 1.Through the diagnosis and treatment of this patient,we systematically learned andrecognized the rare disease group of “hypermethionemia and related diseases”.2.Although there was no recommendation about hypermethionemia in neonatalscreening,but the detection of "methionine" is important for the detection of CBS deficiency.Therefore,qualified families are encouraged to actively carry out newborn screening to reduce birth defects.3.In this case,the child were characterized by elevated plasma methionine.We finally found new mutations by gene sequencing + MLPA technology and made the mostappropriate diagnosis and treatment for the children.It fully demonstrates the importance of tracing the cause of clinical abnormality and interpreting geneticreportsreasonably.