Fanconi-Bickel Syndrome (FBS) is a rare genetic disorder, impacting both the kidneys and liver, and is marked by the abnormal processing of glucose and phosphate chemicals in the body. Protheragen provides comprehensive preclinical drug and therapy development services specifically tailored to address the unique mechanisms of Fanconi-Bickel syndrome, with a focused expertise on renal-related therapeutic strategies.
Overview of Fanconi-Bickel Syndrome (FBS)
FBS is considered an ultra-rare recessive glycogen storage disorder due to its rare occurrence. FBS is defined by a distinctive triad of clinical features: Renal Fanconi syndrome which incorporates phosphaturia, aminoaciduria, glycosuria, and proximal tubular acidosis, hepatorenal glycogen accumulation with hepatomegaly, and marked hypoglycemia in addition to galactose intolerance. Its average prevalence is lower than 1 in 1,000,000 live births. However, in certain populations with founder effects, the prevalence is higher. Though often not classified as a lethal early-life disorder, in the long term FBS could result in substantial life-altering complications such as severe growth retardation, rickets, and progressive renal dysfunction from the chronic proximal tubular stress. This highlights FBS as a significant inherited renal and metabolic disorder.
Pathogenesis of Fanconi-Bickel Syndrome (FBS)
Biallelic loss of function mutations in the SLC2A2 gene, responsible for the glucose transporter 2 (GLUT2) protein, underlies the etiology of Fanconi-Bickel Syndrome (BFS). GLUT2 is a facilitative glucose transporter found mainly in the hepatocytes, pancreatic beta cells, enterocytes of the small intestine, and importantly, renal proximal tubular cells. As an integral part of the glucose transport system, GLUT2 is responsible for the transport of glucose, galactose, and fructose in a large capacity, without the need for insulin.
Fig.1 Role of glucose transporter 2 (GLUT2) in pancreatic β cell glucose-stimulated insulin secretion. (Hartill
et al., 2017)
Pathological processes stemming from mutations in GLUT2 protein are renal and hepatic in nature. GLUT2 protein mutations in the kidneys lead to a lack of glucose resorption due to lack of functional GLUT2 at the proximal tubule's basolateral membrane. This leads to the renal Vaughan syndrome characterized by glycosuria, phosphaturia, and aminoaciduria. In hepatocytes, lack of GLUT2 leads to the inability to release glucose into the blood, hence accumulating then converting it to glycogen, leading to hepatomegaly. Such dysfunction in these two organs illustrates the importance of the GLUT2 transporter for metabolic homeostasis and renal tubular function.
Therapeutics Development for Fanconi-Bickel Syndrome (FBS)
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Sodium bicarbonate |
Renal tubular HCO3- transporter (SLC4A4) |
Corrects proximal renal tubular acidosis and maintains blood pH balance |
Approved |
| Calcitriol |
Vitamin D receptor (VDR) |
Activates VDR to enhance intestinal calcium absorption; treats rickets and osteomalacia |
Approved |
| 4-Phenylbutyrate (4-PBA) |
Mutant GLUT2 protein (p.Thr310Ile) |
Molecular chaperone corrects folding defects in GLUT2 missense mutation; restores membrane localization in vitro |
Preclinical |
| rAAV8-hGLUT2 |
SLC2A2 mRNA |
AAV8 vector delivers functional GLUT2 gene; reduces hepatic glycogen by 80% and restores glucose homeostasis in Glut2-/- mice |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is a comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for Fanconi-Bickel syndrome. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture important features of this disorder, with a particular focus on its severe renal manifestations.
Therapeutic Development Platforms for Fanconi-Bickel Syndrome
Disease Models Development for Fanconi-Bickel Syndrome
Protheragen offers innovative and comprehensive disease models to advance preclinical research into Fanconi-Bickel syndrome. Our platform integrates advanced cell-based models, kidney organoids, and animal models. These models are meticulously developed and characterized for robust target identification and comprehensive therapeutic efficacy testing for Fanconi-Bickel syndrome -specific pathways, particularly those impacting renal and metabolic health.
Cell-based & Organoid Models
- Patient-Derived Primary Hepatocytes
- Primary Renal Proximal Tubule Epithelial Cells
- iPSC-Derived Hepatocyte-like Cells
- GLUT2 KO/KI iPSC Kidney Organoid
Animal Models
- Global Slc2a2 KO Mouse
- Hepatocyte-Specific Slc2a2 cKO Mouse
- Renal Proximal Tubule-Specific Slc2a2 cKO
- Slc2a2 Pathogenic Mutation Knock-in Mouse
- Slc2a2 Knockout Rat
Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Metabolic Stability Assay
- Plasma Protein Binding
- Renal Tubular Epithelial Cell Uptake & Efflux
- Drug-Transporter Interaction Profiling
- Cellular Permeability
In Vivo Pharmacokinetics Services
- Systemic Pharmacokinetics
- Kidney Tissue Distribution and Retention
- Renal Clearance and Excretion Studies
- Urinary Metabolite Profiling
- Blood-to-Plasma Ratio
Protheragen's integrated preclinical development solutions are specifically designed for research in rare kidney diseases and complex developmental disorders like Fanconi-Bickel syndrome. We specialize in comprehensive disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your therapeutic investigations from initial target validation to IND-enabling studies.
Contact us today to accelerate your Fanconi-Bickel syndrome research with end-to-end solutions.
References
- Gupta, A., et al. "Meckel-Gruber Syndrome: Prenatal Diagnosis of a Lethal Ciliopathy with Multisystem Anomalies." J Obstet Gynaecol Can 47.1 (2025): 102716.
- Hartill, V., et al. "Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances." Front Pediatr 5 (2017): 244.
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only and cannot be used to diagnose, treat or manage patients.
