Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia

<p dir="ltr">Accumulation of glycogen in the kidney and liver is the main feature of Fanconi–Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indel...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Sanaa Sharari (12561952) (author)
مؤلفون آخرون: Mohamad Abou-Alloul (18719020) (author), Khalid Hussain (110443) (author), Faiyaz Ahmad Khan (18719023) (author)
منشور في: 2020
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author Sanaa Sharari (12561952)
author2 Mohamad Abou-Alloul (18719020)
Khalid Hussain (110443)
Faiyaz Ahmad Khan (18719023)
author2_role author
author
author
author_facet Sanaa Sharari (12561952)
Mohamad Abou-Alloul (18719020)
Khalid Hussain (110443)
Faiyaz Ahmad Khan (18719023)
author_role author
dc.creator.none.fl_str_mv Sanaa Sharari (12561952)
Mohamad Abou-Alloul (18719020)
Khalid Hussain (110443)
Faiyaz Ahmad Khan (18719023)
dc.date.none.fl_str_mv 2020-08-31T09:00:00Z
dc.identifier.none.fl_str_mv 10.3390/ijms21176286
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Fanconi_Bickel_Syndrome_A_Review_of_the_Mechanisms_That_Lead_to_Dysglycaemia/25958185
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Fanconi–Bickel Syndrome (FBS)
SLC2A2 mutation
GLUT2 dysfunction
dysglycaemia
liver
pancreatic β cell
cAMP
insulin secretion
birth weight
hepatomegaly
dc.title.none.fl_str_mv Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Accumulation of glycogen in the kidney and liver is the main feature of Fanconi–Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indels, splice site, and compound heterozygous variants have all been identified in SLC2A2 gene of FBS cases. Approximately 144 FBS cases with 70 different SLC2A2 gene variants have been reported so far. SLC2A2 encodes for glucose transporter 2 (GLUT2) a low affinity facilitative transporter of glucose mainly expressed in tissues playing important roles in glucose homeostasis, such as renal tubular cells, enterocytes, pancreatic β-cells, hepatocytes and discrete regions of the brain. Dysfunctional mutations and decreased GLUT2 expression leads to dysglycaemia (fasting hypoglycemia, postprandial hyperglycemia, glucose intolerance, and rarely diabetes mellitus), hepatomegaly, galactose intolerance, rickets, and poor growth. The molecular mechanisms of dysglycaemia in FBS are still not clearly understood. In this review, we discuss the physiological roles of GLUT2 and the pathophysiology of mutants, highlight all of the previously reported SLC2A2 mutations associated with dysglycaemia, and review the potential molecular mechanisms leading to dysglycaemia and diabetes mellitus in FBS patients.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms21176286" target="_blank">https://dx.doi.org/10.3390/ijms21176286</a></p>
eu_rights_str_mv openAccess
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identifier_str_mv 10.3390/ijms21176286
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25958185
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spelling Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to DysglycaemiaSanaa Sharari (12561952)Mohamad Abou-Alloul (18719020)Khalid Hussain (110443)Faiyaz Ahmad Khan (18719023)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsFanconi–Bickel Syndrome (FBS)SLC2A2 mutationGLUT2 dysfunctiondysglycaemialiverpancreatic β cellcAMPinsulin secretionbirth weighthepatomegaly<p dir="ltr">Accumulation of glycogen in the kidney and liver is the main feature of Fanconi–Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indels, splice site, and compound heterozygous variants have all been identified in SLC2A2 gene of FBS cases. Approximately 144 FBS cases with 70 different SLC2A2 gene variants have been reported so far. SLC2A2 encodes for glucose transporter 2 (GLUT2) a low affinity facilitative transporter of glucose mainly expressed in tissues playing important roles in glucose homeostasis, such as renal tubular cells, enterocytes, pancreatic β-cells, hepatocytes and discrete regions of the brain. Dysfunctional mutations and decreased GLUT2 expression leads to dysglycaemia (fasting hypoglycemia, postprandial hyperglycemia, glucose intolerance, and rarely diabetes mellitus), hepatomegaly, galactose intolerance, rickets, and poor growth. The molecular mechanisms of dysglycaemia in FBS are still not clearly understood. In this review, we discuss the physiological roles of GLUT2 and the pathophysiology of mutants, highlight all of the previously reported SLC2A2 mutations associated with dysglycaemia, and review the potential molecular mechanisms leading to dysglycaemia and diabetes mellitus in FBS patients.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms21176286" target="_blank">https://dx.doi.org/10.3390/ijms21176286</a></p>2020-08-31T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms21176286https://figshare.com/articles/journal_contribution/Fanconi_Bickel_Syndrome_A_Review_of_the_Mechanisms_That_Lead_to_Dysglycaemia/25958185CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259581852020-08-31T09:00:00Z
spellingShingle Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
Sanaa Sharari (12561952)
Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Fanconi–Bickel Syndrome (FBS)
SLC2A2 mutation
GLUT2 dysfunction
dysglycaemia
liver
pancreatic β cell
cAMP
insulin secretion
birth weight
hepatomegaly
status_str publishedVersion
title Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
title_full Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
title_fullStr Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
title_full_unstemmed Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
title_short Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
title_sort Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia
topic Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical biochemistry and metabolomics
Fanconi–Bickel Syndrome (FBS)
SLC2A2 mutation
GLUT2 dysfunction
dysglycaemia
liver
pancreatic β cell
cAMP
insulin secretion
birth weight
hepatomegaly