Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in FBP1
Author:
Emecen Sanli Merve1ORCID, Cengiz Basak1, Kilic Ayse1, Ozsaydi Ekin1, Inci Asli1ORCID, Okur Ilyas1, Tumer Leyla1, Lebigot Elise2, Ezgu Fatih1
Affiliation:
1. Department of Inborn Errors of Metabolism , Gazi University School of Medicine , Ankara , Turkey 2. Bicêtre Hospital , AP-HP, Biochemistry Department , 94275 Le Kremlin-Bicêtre , France
Abstract
Abstract
Objectives
Fructose 1,6 bisphosphatase (FBPase) deficiency is a rare autosomal recessively inherited metabolic disease. It is encoded by FBP1, and the enzyme catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose 6-phosphate. Patients with recurrent episodes of metabolic acidosis, hypoglycemia, hypertriglyceridemia, and hyperketonemia are present.
Methods
In this study, we describe the clinical, biochemical, and molecular genetic features of six unrelated Turkish patients from six different families who were genetically diagnosed with FBPase deficiency in our clinic between 2008 and 2020. Their clinical and laboratory data were collected retrospectively. Next-generation sequencing (NGS) was performed for the molecular genetic analysis.
Results
All patients were hospitalized with recurrent hypoglycemia and metabolic acidosis episodes. Three out of six patients were presented in the neonatal period. The mean age at diagnosis was 26 months. NGS revealed a known homozygous gross deletion including exon 2 in three patients (50%), a known homozygous c.910_911dupTT pathogenic variant in one patient (16%), a novel homozygous c.651_653delCAGinsTAA likely pathogenic variant, and another novel homozygous c.705+5G>A splice site variant. Leukocyte FBPase analysis detected no enzyme activity in the patient with homozygous c.705+5G>A splice site variant.
Conclusions
We identified two novel mutations in this study. One of them is a splice site mutation which is five bases downstream of the exon, and the other one is an indel mutation. Both of the splice site and indel mutations are exceedingly rare in FBP1, and to the best of our knowledge, there are second splice site and indel variants reported in the literature. Exon 2 deletion is the most common mutation consistent with the previous reports in Turkish patients. FBPase is a frequent cause of hypoglycemia and metabolic acidosis, and the widespread use of molecular genetic analysis would contribute to the enlightenment of advanced genetic factors and possible genotype/phenotype correlation.
Publisher
Walter de Gruyter GmbH
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Pediatrics, Perinatology and Child Health
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