Acquired growth hormone deficiency in Fanconi-Bickel syndrome

Scully, Kevin; Wolfsdorf, Joseph I.; Dedekian, Michael

doi:10.1136/bcr-2021-246212

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Mutations in glucose transporter 2 (GLUT2) were first reported in three FBS patients, including the first patient in 1997 [ 2 ]. More than 100 FBS cases with different SLC2A2 mutations (missense, nonsense, Fs/InDel, intronic, and compound heterozygous) have been reported to date [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The SLC2A2 gene encodes for low-affinity-facilitated glucose transporter 2 (GLUT2, SLC2A2-201 ENST00000314251.8) [ 3 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome

et al. 2022

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Fanconi–Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the SLC2A2 gene. SLC2A2 encodes for the glucose transporter GLUT2 and is expressed in tissues that are involved in glucose homeostasis. The molecular mechanisms of dysglycemia in FBS are still not clearly understood. In this study, we report two cases of FBS with classical phenotypes of FBS associated with dysglycemia. Genomic DNA was extracted and analyzed by whole-genome and Sanger sequencing, and patient PBMCs were used for molecular analysis. One patient had an exonic SLC2A2 mutation (c.1093C>T in exon 9, R365X), while the other patient had a novel intronic SLC2A2 mutation (c.613-7T>G). Surprisingly, the exonic mutation resulted in the overexpression of dysfunctional GLUT2, resulting in the dysregulated expression of other glucose transporters. The intronic mutation did not affect the coding sequence of GLUT2, its expression, or glucose transport activity. However, it was associated with the expression of miRNAs correlated with type 1 diabetes mellitus, with a particular significant overexpression of hsa-miR-29a-3p implicated in insulin production and secretion. Our findings suggest that SLC2A2 mutations cause dysglycemia in FBS either by a direct effect on GLUT2 expression and/or activity or, indirectly, by the dysregulated expression of miRNAs implicated in glucose homeostasis.

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Section: Introductionmentioning

confidence: 99%

Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome

et al. 2022

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“…Mutations in GLUT2 were rst reported in three FBS patients, including the rst patient in 1997 [2]. More than 100 FBS cases with different SLC2A2 mutations (missense, nonsense, Fs/InDel, intronic, and compound heterozygous) have been reported until now [3][4][5][6][7][8][9]. The SLC2A2 gene encodes for low-a nity facilitated glucose transporter 2 (GLUT2) (SLC2A2-201 ENST00000314251.8) [3,10].…”

Section: Introductionmentioning

confidence: 99%

Understanding the role of GLUT2 in dysglycemia associated with Fanconi-Bickel syndrome

Sharari

Kabeer

Mohammed

et al. 2022

Preprint

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Fanconi–Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the SLC2A2 gene. SLC2A2 encodes for the glucose transporter GLUT2 and is expressed in tissues that are involved in glucose homeostasis. The molecular mechanisms of dysglycemia in FBS are still not clearly understood. In this study, we report two cases of FBS with classical phenotypes of FBS associated with dysglycemia. Genomic DNA was extracted and analyzed by whole-genome and Sanger sequencing, and patient PBMCs were used for molecular analysis. One patient had an exonic SLC2A2 mutation (c.1093C > T in exon 9, R365X), while the other patient had a novel intronic SLC2A2 mutation (c.613-7T>G). Surprisingly, the exonic mutation resulted in the overexpression of dysfunctional GLUT2, resulting in the dysregulated expression of other glucose transporters. The intronic mutation did not affect the coding sequence of GLUT2, its expression, or glucose transport activity. However, it was associated with the expression of miRNAs correlated with type 1 diabetes mellitus, with a particular significant overexpression of hsa-miR-29a-3p implicated in insulin production and secretion. Our findings suggest that SLC2A2 mutations cause dysglycemia in FBS either by a direct effect on GLUT2 expression and/or activity or, indirectly, by the dysregulated expression of miRNAs implicated in glucose homeostasis.

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Endocrine involvement in hepatic glycogen storage diseases: pathophysiology and implications for care

Rossi,

Simeoli,

Pivonello

et al. 2024

Rev Endocr Metab Disord

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Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.g., hypothalamic‑pituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment. Being aware of the endocrine abnormalities occurring in hepatic GSDs is essential (1) to provide optimized medical care to this group of individuals and (2) to drive research aiming at understanding the disease pathophysiology. In this review, a thorough description of the endocrine manifestations in individuals with hepatic GSDs is presented, including pathophysiological and clinical implications.

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Acquired growth hormone deficiency in Fanconi-Bickel syndrome

Cited by 3 publications

References 10 publications

Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome

Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome

Understanding the role of GLUT2 in dysglycemia associated with Fanconi-Bickel syndrome

Endocrine involvement in hepatic glycogen storage diseases: pathophysiology and implications for care

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