Late Diagnosis of Fanconi-Bickel Syndrome

Gupta, Nakul; Nambam, Bimota; Weinstein, David A.; Shoemaker, Lawrence

doi:10.1177/2326409816679430

Cited by 10 publications

(6 citation statements)

References 28 publications

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“…With early and appropriate treatment, the overall prognosis is very good, and survival to adulthood is favorable [10]. We are certain the prognosis of our patient is good and that we shall have catch up in growth for weight and height and development, as evidenced with the weight gain after initiation of therapy.…”

Section: Discussionmentioning

confidence: 78%

“…We believe that the abdominal distension was due to hepatic glycogen accumulation in his liver, as shown by the grossly enlarged liver on abdominal ultrasound scanning. Our patient also presented with fasting ketotic hypoglycemia which is commonly noted [8][9][10]. Genetic testing for confirmation was not done due to the unavailability of the appropriate test in our setting.…”

Section: Discussionmentioning

confidence: 99%

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Fanconi–Bickel syndrome in a Ugandan child – diagnostic challenges in resource-limited settings: a case report

et al. 2020

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Background Fanconi–Bickel syndrome is an autosomal recessive disorder of glucose metabolism. It is an extremely rare disorder. Most cases have been reported in consanguineous communities. None of the cases have been reported in Black Africans in sub-Saharan Africa. This case was diagnosed 3 years after initial presentation due to diagnostic challenges and limited awareness of similar metabolic syndromes in our setting. Case presentation We report the case of a 4-year-old boy, born to non-consanguineous Black African parents, who presented with failure to thrive and rachitic features in infancy. Clinical, laboratory, and radiological features were indicative of Fanconi–Bickel syndrome. No genetic testing was done. The diagnosis was made 3 years after the initial presentation due to diagnostic challenges. He showed clinical improvement with the institution of a galactose-free diet. Conclusion Fanconi–Bickel syndrome occurs even in non-consanguineous Black African populations. Therefore, clinicians in resource-poor settings should raise their index of suspicion for such metabolic disorders in settings with a high prevalence of failure to thrive among children.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Fanconi–Bickel syndrome in a Ugandan child – diagnostic challenges in resource-limited settings: a case report

et al. 2020

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“…The demographic information in Table S1 shows that FBS has been reported in every major human ethnic group. The first case of FBS was reported in Switzerland in 1949 (Fanconi & Bickel, ); the first Chinese patients diagnosed with FBS was in 2011 (Su et al, ); and the first African American patient diagnosed with FBS was in 2016 (Gupta, Nambam, Weinstein, & Shoemaker, ). Our updated FBS case list includes more than ten novel amino acid variants that were published after the last published FBS review in 2002 (Santer et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we performed a comprehensive functional characterization of 17 SLC2A2 missense and in‐frame indel mutant transporters associated with a range of FBS phenotypes and five SLC2A2 missense variants associated with various metabolic perturbations (e.g., T2D, elevated HbA1c concentration, increased fasting glucose levels). Previously, only five FBS mutant transporters had been characterized out of over 40 known variants and to our knowledge, only three SLC2A2 missense variants associated with metabolic traits have been characterized (c.329C>T, p.Thr110Ile; c.203C>T, p.Pro68Leu and c.589G>A, p.Val197Ile (Table S3 and Figure S5; Abbasi et al, ; Amita et al, ; Gupta et al, ; Michau et al, ; Pogoriler et al, ; Wang et al, ). Generally, in order for FBS to manifest in an individual, the person must be homozygous or compound heterozygous with two deleterious SLC2A2 variants.…”

Section: Discussionmentioning

confidence: 99%

Functional and structural analysis of rareSLC2A2variants associated with Fanconi‐Bickel syndrome and metabolic traits

et al. 2019

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Deleterious variants in SLC2A2 cause Fanconi‐Bickel Syndrome (FBS), a glycogen storage disorder, whereas less common variants in SLC2A2 associate with numerous metabolic diseases. Phenotypic heterogeneity in FBS has been observed, but its causes remain unknown. Our goal was to functionally characterize rare SLC2A2 variants found in FBS and metabolic disease‐associated variants to understand the impact of these variants on GLUT2 activity and expression and establish genotype‐phenotype correlations. Complementary RNA‐injected Xenopus laevis oocytes were used to study mutant transporter activity and membrane expression. GLUT2 homology models were constructed for mutation analysis using GLUT1, GLUT3, and XylE as templates. Seventeen FBS variants were characterized. Only c.457_462delCTTATA (p.Leu153_Ile154del) exhibited residual glucose uptake. Functional characterization revealed that only half of the variants were expressed on the plasma membrane. Most less common variants (except c.593 C>A (p.Thr198Lys) and c.1087 G>T (p.Ala363Ser)) exhibited similar GLUT2 transport activity as the wild type. Structural analysis of GLUT2 revealed that variants affect substrate‐binding, steric hindrance, or overall transporter structure. The mutant transporter that is associated with a milder FBS phenotype, p.Leu153_Ile154del, retained transport activity. These results improve our overall understanding of the underlying causes of FBS and impact of GLUT2 function on various clinical phenotypes ranging from rare to common disease.

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“…Global Glut2 knockout mice [ 7 ] exhibit hypoinsulinemia, hyperglycemia, and die within three weeks after birth. In contrast, humans with GLUT2 deficiency show good prognosis [ 8 ], although they may experience transient neonatal diabetes [ 9 , 10 ]. Humans and rodents have differential expression of β-cell GLUT2 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice

et al. 2023

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Objective: Glucose transporter 2 (GLUT2) is expressed in the pancreatic β-cell, intestine, liver, and kidney in mice. Although GLUT2 is considered as a major regulator of insulin secretion, in vivo contribution of β-cell Glut2 to glucose-stimulated insulin secretion and systemic glucose homeostasis is undefined. Therefore, the main objective of this study is to determine the role of β-cell Glut2 in regulating insulin secretion and blood glucose levels in mice. Methods: We produced mice in which we can knock down Glut2 at a desired time specifically in β-cells (β-Glut2 KD) by crossing Glut2LoxP/LoxP mice with Ins1CreERT2 mouse strain and using the Cre-Lox recombination technique. We measured fasting blood glucose levels, glucose tolerance, and glucose-stimulated insulin secretion in the β-Glut2 KD mice. We used qRT-PCR and immunofluorescence to validate the deficiency of β-cell Glut2 in β-Glut2 KD mice. Results: We report that both male and female β-Glut2 KD mice have normal glucose-stimulated insulin secretion. Moreover, the β-Glut2 KD mice exhibit normal fasting blood glucose levels and glucose tolerance. The β-Glut2 KD mice have upregulated GLUT1 in islets. Conclusions: Our findings demonstrate that normal β-cell Glut2 expression is not essential for regulating glucose-stimulated insulin secretion and systemic glucose homeostasis in mice. Therefore, the currently assumed role of β-cell GLUT2 in regulating insulin secretion and blood glucose levels needs to be recalibrated. This will allow an opportunity to determine the contribution of other β-cell glucose transporters or factors whose normal expression may be necessary for mediating glucose stimulated insulin secretion.

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Late Diagnosis of Fanconi-Bickel Syndrome

Cited by 10 publications

References 28 publications

Fanconi–Bickel syndrome in a Ugandan child – diagnostic challenges in resource-limited settings: a case report

Fanconi–Bickel syndrome in a Ugandan child – diagnostic challenges in resource-limited settings: a case report

Functional and structural analysis of rareSLC2A2variants associated with Fanconi‐Bickel syndrome and metabolic traits

Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice

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