OBJECTIVE: To explore the clinical features and genetic basis of a child with Galactosemia. METHODS: A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing. RESULTS: Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR). CONCLUSION Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.
Child ; Female ; Humans ; Galactosemias/genetics* ; Genetic Testing ; Health Status ; Methionine ; Muscle Hypotonia ; Mutation

OBJECTIVETo explore the genetic basis of two neonates suspected for galactosemia.

METHODSNext generation sequencing(NGS) was used to screen the whole exome of the neonates. Suspected mutation was validated by PCR and Sanger sequencing. Potential impact of novel mutation was predicted by using PolyPhen-2, MutationTaste and SIFT software.

RESULTSBoth neonates harbored compound heterozygous mutations of the GALT gene inherited from their parents. One has inherited two novel mutations c.564G>C(p.Q188H) and c.116A>T(p.D39V) respectively from his father and mother. The other has inherited mutations c.754C>T(p.Q252X) and c.904+1G>T from her father and mother, respectively.

CONCLUSIONThe galactosemia in the two neonates may be attributed to compound heterozygous mutations of the GALT gene. This is the first domestic report of using the NGS for the diagnosis of galactosemia.

Female ; Galactosemias ; diagnosis ; Heterozygote ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Infant, Newborn ; Male ; Mutation ; UTP-Hexose-1-Phosphate Uridylyltransferase ; genetics