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
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Merve Emecen Sanli
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Basak Cengiz
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.
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Research funding: We did not receive funding.
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Author contributions: All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Conflict of interest statement: There are no conflicts of interest.
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Informed consent: Written informed consent was obtained from the parents and the patients who participated in this study.
References
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© 2022 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review Article
- Nephrogenic diabetes insipidus: a comprehensive overview
- Original Articles
- Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
- Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
- Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
- Evaluation of patients with phenylalanine metabolism disorder: a single center experience
- The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
- Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
- Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
- Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
- 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
- Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
- Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
- Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
- Letter to the Editor
- Correspondence on “Obesity after the Covid-19 pandemic”
- Case Reports
- An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
- Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
- Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
- Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
Artikel in diesem Heft
- Frontmatter
- Review Article
- Nephrogenic diabetes insipidus: a comprehensive overview
- Original Articles
- Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
- Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
- Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
- Evaluation of patients with phenylalanine metabolism disorder: a single center experience
- The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
- Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
- Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
- Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
- 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
- Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
- Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
- Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
- Letter to the Editor
- Correspondence on “Obesity after the Covid-19 pandemic”
- Case Reports
- An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
- Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
- Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
- Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
