Fanconi-Bickel syndrome in two Palestinian children: marked phenotypic variability with identical mutation

Abstract

BackgroundFanconi-Bickel syndrome (FBS, OMIM 227810) is a rare autosomal recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a member of the facilitative glucose transporter family (Santer et al. J Inherit Metab Dis 21:191–194, 1998). The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal renal tubular dysfunction, rickets and severe short stature.Case presentationWe report 2 Palestinian patients from 2 families who were homozygous for the mutation p.R301X (C>T) in exon 7of GLUT2 gene. Patient 1 showed clinical and laboratory improvement with age characterized by normal growth and resolution of rickets. Patient 2 had severe phenotype characterized by progressive weight loss, persistent metabolic acidosis, marked polyuria and clinical and laboratory findings of rickets progressing to death at age 10 months.ConclusionThis report further expands the clinical spectrum of FBS even with identical mutations. Other yet unknown genetic, environmental or stochastic factors may be responsible for phenotypic variability

Fanconi syndrome and neonatal diabetes: phenotypic heterogeneity in patients with GLUT2 defects

“…Parents were heterozygous carriers while affected elder siblings were not tested confirmed when the youngest sibling presented with neonatal diabetes, an entity with relatively fewer monogenic etiologies compared to Fanconi syndrome [7,8]. While phenotypic heterogeneity is described for mutations in SLC2A2 encoding GLUT2, variations in phenotype within families, development of diabetes and neonatal presentation are uncommon [2,5,[9][10][11].…”

“…While multiple mutations are described, there are few mutational hotspots and no genotype-phenotype correlation [2][3][4]. Variation in disease severity with identical mutations has also been reported [2,5]. Patients typically present in infancy with vomiting, growth failure and refractory rickets [3].…”

First case of Fanconi-Bickel syndrome genetically diagnosed in Sri Lanka

“…Fanconi-Bickel syndrome (FBS) was first described in 1949 in a Swiss boy who was followed up over five decades 1 . Less than 200 FBS patients have been reported in the literature [2][3][4][5] . Extensive literature survey did not show any cases of FBS in Sri Lanka.…”

Renal tubular acidosis in pediatrics: A review article

“…14 18 Fanconi-Bickel syndrome missense mutation in SLC2A2, 19 is a rare autosomal recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a member of the facilitative glucose transporter family. 20 The most common type is cystinosis caused by CTNS mutation and is a lysosomal storage disorder. 21 It usually responds to cysteamine.…”

“…22 In 2 Palestinian patients from 2 families, homozygosity of genes were noted in p.R301X (C>T) in exon 7 of GLUT2 gene. 20 It presents with fasting hypoglycaemia, post-prandial hyperglycaemia, delay in motor function, distended abdomen, unable to gain weight and renal tubular acidosis. 23 B-Inborn error of metabolism including glucose-galactose malabsorption and congenital NBCe1A deficiency, cystinosis and tyrosinemia as example.…”