Amino Acid Metabolism, Inborn Errors ; genetics ; Female ; Glycine N-Methyltransferase ; deficiency ; genetics ; Humans ; Infant, Newborn ; Mutation

OBJECTIVETo detect potential mutations of MAT1A gene in a child suspected with simple hypermethioninemia by MS/MS neonatal screening.

METHODSClinical data of the child was collected. Genomic DNA was extracted by a standard method and subjected to targeted sequencing using an Ion AmpliseqInherited Disease Panel. Detected mutations were verified by Sanger sequencing.

RESULTSThe child showed no clinical features except evaluated methionine. A novel compound mutation of the MAT1A gene, i.e., c.345delA and c.529C>T, was identified in the child. His father and mother were found to be heterozygous for the c.345delA mutation and c.529C>T mutation, respectively.

CONCLUSIONThe compound mutation c.345delA and c.529C>T of the MAT1A gene probably underlie the disease in the child. The semi-conductor sequencing has provided an important means for the diagnosis of hereditary diseases.

Amino Acid Metabolism, Inborn Errors ; genetics ; pathology ; Base Sequence ; DNA Mutational Analysis ; methods ; Family Health ; Fathers ; Female ; Genetic Predisposition to Disease ; genetics ; Glycine N-Methyltransferase ; deficiency ; genetics ; Heterozygote ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; genetics ; pathology ; Male ; Methionine Adenosyltransferase ; genetics ; Mothers ; Mutation

OBJECTIVETo analyze the clinical features and SLC25A13 gene mutations of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia.

METHODSThe patient was subjected to physical examination and routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic acids and galactose were analyzed respectively with tandem mass spectrometry and gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was conducted by high resolution melt (HRM) analysis.

RESULTSThe petechiae on the patient's face and platelet count (27×10(9)/L, reference range 100×10(9)/L-300×10(9)/L) supported the diagnosis of immunologic thrombocytopenic purpura (ITP). Laboratory tests found that the patient have abnormal coagulation, cardiac enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry also found methionine to be increased (286 μmol/L, reference ranges 8-35 μmol/L). The patient did not manifest any galactosemia, citrullinemia and tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct sequencing of exon 6 revealed a novel mutation c.495delA. The same mutation was not detected in 100 unrelated healthy controls. Further analysis of her family has confirmed that the c.495delA mutation has derived from her farther, and that the IVS16ins3kb was derived from her mother.

CONCLUSIONThe clinical features and metabolic spectrum of citrin deficiency can be variable. The poor prognosis and severity of clinical symptoms of the patient may be attributed to the novel c.495delA mutation.

Amino Acid Metabolism, Inborn Errors ; genetics ; pathology ; Calcium-Binding Proteins ; deficiency ; genetics ; DNA Mutational Analysis ; methods ; Female ; Glycine N-Methyltransferase ; deficiency ; genetics ; Humans ; Infant ; Mitochondrial Membrane Transport Proteins ; genetics ; Organic Anion Transporters ; deficiency ; genetics ; Pedigree ; Purpura ; genetics ; pathology ; Seizures ; genetics ; pathology