ESPE Abstracts (2018) 89 P-P2-194

Molecular Defects Identified by Whole Exome Sequencing in a Chinese Boy with Fructose-1,6-Bisphosphatase Deficiency

Zhuo Huanga,b, Jin Wua,b & Chengfa Xianga,b

aDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; bMinistry of Education Key Laboratory of Women and Children’s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, China

Backgroud: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal recessive inherited disorder of gluconeogenesis, which caused by the mutations in the FBP1 gene. FBPase deficiency is characterized by recurrent episodes of hypoglycemia with metabolic and lactic acidosis. If diagnosed early, the prognosis of this disorder is excellent by the prevention of hypoglycemia and avoidance of intake of fructose and sucrose. However, the misdiagnosis of FBPase deficiency is not rare in clinical practice because of the limited experiences in Chinese patients. This misdiagnosis could be avoided by using next generation sequencing, which have been shown an excellent performance for detecting mutations in suspected cases of inborn errors of metabolism in previous studies. Here, we report a Chinese boy with FBPase deficiency detected by whole exome sequencing (WES).

Methods: The clinical and laboratory data of this Chinese boy were collected retrospectively. WES was performed to identify his potential genetic etiology and the putative pathogenic variants were validated by Sanger sequencing.

Results: A 16-month-old boy was repeatedly admitted to hospitals with recurrent onset of lethargy every time after febrile infectious disease and recurrent vomiting during 6 months. His physical examination showed mild hepatomegaly, and he had normal physical and mental development. The laboratory findings revealed severe hypoglycemia, metabolic acidosis, hyperlactacidemia and abnormal liver function. After intravenous infusion of glucose, bicarbonate and antibiotics, there was a dramatic clinical improvement in a short time. WES identified compound heterozygous mutations in the FBP1 gene of c.841G>A (inherited from his father) and c.778 G>A (inherited from his mother). Both the mutations were known pathogenically. After the diagnosis was established, the boy was prescribed dietary restrictions. In the last 6 months follow-up, he had no attack.

Conclusions: FBPase deficiency needs to be considered in individuals with recurrent hypoglycemia and metabolic acidosis. Our results illustrate that WES could become a powerful tool for molecular diagnosis of Mendelian disease with unknown etiology, which may contribute to better treatment, genetic counseling and prenatal diagnosis.

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