Splicing abnormalities caused by a novel mutation in the PHKA2 gene in children with glycogen storage disease type IX / 中华肝脏病杂志

Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.

A single-center retrospective analysis of 46 children with aerophagia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of aerophagia in children.@*MEYJODS@#A retrospective analysis was performed on the medical data of 46 children with aerophagia who were diagnosed and treated in Children's Hospital Affiliated to Nanjing Medical University from October 2011 to September 2019.@*RESULTS@#Among these 46 children, 15 (33%) had Tourette syndrome. Abdominal distension was the most common symptom and was observed in 45 children (98%). The 24-hour esophageal multichannel intraluminal impedance monitoring showed a mean number of 341 times of air swallowing and a mean number of 212 times of gas reflux, and 95% of gas refluxes occurred in the upright body position. Compared with those without Tourette syndrome, the children with Tourette syndrome had a significantly higher incidence rate of air swallowing symptoms (67% vs 6%, P<0.001), but there were no significant differences in other symptoms and the results of 24-hour esophageal impedance. Dietary adjustment, psycho-behavioral therapy, and drug intervention significantly improved the scores of clinical symptoms and quality of life, among which psycho-behavioral therapy was an important intervention measure.@*CONCLUSIONS@#Some children with aerophagia may have Tourette syndrome, and such children are more likely to have air swallowing symptoms. Psycho-behavioral therapy is one of the most important treatment methods, and children with aerophagia tend to have a good prognosis after treatment.