Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant
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Hajira Batool
Abstract
Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2) protein. The clinical manifestations include hepatomegaly, conditional hypo/hyperglycemia, rickets, short stature and proximal renal tubular dysfunction. GLUT2 regulates monosaccharide homeostasis through sugar sensing and transmembrane transportation during high/low glucose levels. In the current study, we present two siblings suffering from FBS. The patients presented with doll-like facies, failure to gain weight and height, abdominal distension and firm hepatomegaly. The family had a history of deaths of twin male siblings in the neonatal period and twin female siblings at ages 10 months and 2.5 years, respectively. Clinical presentation and biochemical investigations including a complete blood count, electrolytes, liver and renal function tests suggested FBS. Mutation screening of SLC2A2 confirmed the diagnosis with identification of a novel homozygous splice site variant predicting an in-frame deletion [p.(Gly166-S169del)] in the GLUT2 protein. The in-silico analysis predicted the variant to affect the three-dimensional conformation of the fourth transmembrane helix of the encoded protein, rendering the non-functionality of GLUT2 in both patients of the family under study.
Acknowledgments
We are thankful to all the members of the affected family who participated in the study.
Author contributions: Hajira Batool: Data curation, methodology, writing – original draft, review and edit. Bibi Zubaida: Patient recruitment, methodology, conceptualization. Muhammad Almas Hashmi: Patient recruitment, conceptualization, clinical and diagnostic study. Muhammad Naeem: Conceptualization, funding acquisition, methodology, supervision, writing – review and edit. All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Hypo- and hyperthyroidism in early life – new developments
- Letters to the Editor
- Optic nerve sheath diameter appraisal in children affected by diabetic ketoacidosis
- Optic nerve sheath diameter ultrasound measurement to evaluate cerebral edema in children with diabetic ketoacidosis
- Original Articles
- Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy
- Phenylketonuric patients represent their disease
- Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1
- Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant
- Sex differences in infant body composition emerge in the first 5 months of life
- Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI)
- Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche
- The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling
- The role of vitamin D replacement therapy in serum FGF23 concentration in children with myelomeningocele compared with healthy children – a preliminary study
- Genetic analyses in a cohort of Portuguese pediatric patients with congenital hypothyroidism
- Congenital hypothyroidism in preterm infants: a 3- to 8-year longitudinal study in southern Thailand
- Case Reports
- A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions
- A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature
- Acquired von Willebrand’s syndrome caused by primary hypothyroidism in a 5-year-old girl
- Double variants in TSHR and DUOX2 in a patient with hypothyroidism: case report
Articles in the same Issue
- Frontmatter
- Editorial
- Hypo- and hyperthyroidism in early life – new developments
- Letters to the Editor
- Optic nerve sheath diameter appraisal in children affected by diabetic ketoacidosis
- Optic nerve sheath diameter ultrasound measurement to evaluate cerebral edema in children with diabetic ketoacidosis
- Original Articles
- Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy
- Phenylketonuric patients represent their disease
- Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1
- Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant
- Sex differences in infant body composition emerge in the first 5 months of life
- Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI)
- Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche
- The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling
- The role of vitamin D replacement therapy in serum FGF23 concentration in children with myelomeningocele compared with healthy children – a preliminary study
- Genetic analyses in a cohort of Portuguese pediatric patients with congenital hypothyroidism
- Congenital hypothyroidism in preterm infants: a 3- to 8-year longitudinal study in southern Thailand
- Case Reports
- A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions
- A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature
- Acquired von Willebrand’s syndrome caused by primary hypothyroidism in a 5-year-old girl
- Double variants in TSHR and DUOX2 in a patient with hypothyroidism: case report
