A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Fanconi Bickel syndrome. the gene mutated in Fanconi-Bickel syndrome, a rare disease usually Fanconi- Bickel syndrome; GLUT2, glucose transporter 2; NPT2. er on these two patients revealed the accumulation of glycogen in hepatocytes. Key words: Fanconi- Bickel syndrome, glucosuria, phosphaturia, glycogenosis.
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PDF | We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A month-old female child presented. PDF | Fanconi-Bickel syndrome (FBS, OMIM ) is a rare type of glycogen storage disease (GSD). It is caused by homozygous or compound heterozygous . Fanconi-Bickel syndrome (FBS) is a rare inherited glycogen storage disease ( GSD) caused by defects in facilitative Glucose Transporter (GLUT2) gene that.
Sakamoto with glycogen storage disorder in the younger child. At 3 months she was noted to have failure to thrive. At that time her serum calcium, phosphorus and S. Cystinosis was considered as a possibility and S. Aminoacidogram demon- e-mail: sheeladr gmail.
Because of elevated Indian J Pediatr tyrosine and normal phenyl alanine levels in plasma, 11 exons including flanking introns were amplified by tyrosinemia was considered but was ruled out later by PCR. Direct sequencing showed that 65 bases were deleted molecular analysis. All massive hepatomegaly of 7 cm below right costal margin 11 exons including flanking introns were amplified by Fig.
Urine thin layer chromatog- raphy detected no sugar other than glucose.
Case Reports in Nephrology
Arterial blood gas analysis revealed metabolic Discussion acidosis pH 7, bicarbonate Although the radiographs were In , Guido Fanconi and Horst Bickel described the first grossly normal, there were biochemical features of hypo- patient with an unusual combination of hepato-renal phospahatemic rickets serum calcium, phosphorus and glycogen accumulation and generalized renal tubulopathy alkaline phosphatase were 9.
Renal and liver function tests were with failure to thrive, rickets, and a protuberant abdomen normal. The condition may be identified during Because of features of Fanconi syndrome glucosuria, routine neonatal screening for galactosemia.
Unlike in protinuria, generalized aminoaciduria and hypophosphate- galactosemia, cataract is not common . Although patients mia metabolic acidosis, hepatomegaly, presence of rickets show signs of generalized tubular dysfunction, the hallmark in elder two children, biopsy proven glycogen storage is the disproportionate loss of glucose both at times when disease in one elder child and consanguinity, Fanconi— plasma glucose is high and low .
Clinical, radiological Bickel Syndrome was considered as the possible diagnosis and biochemical evidence of hypophosphatemic rickets is and was confirmed by molecular analysis of SLC2A2.
All usual. Mild fasting hypoglycemia and hyperlipidemia may Fig. Liver histology shows marked accumulation of Conflict of Interest None.
Although the expression study of mRNA of this patient has not been performed, it is suggested that References normal transcript would be absent. There is no specific treatment. Symptomatic replacement of 1. Fanconi—Bickel syndrome—a water, electrolytes, and vitamin D and restriction of galactose congenital defect of facilitative glucose transport.
Curr Mol Med. These patients should avoid fasting ;— Fanconi G, Bickel H. Die chronische Aminoacidurie Amino- starch at bedtime for prevention of hypoglycemia. Helv Paediatr acta. Since ;— Patient has been followed up to age of 3.
Unfortunately, he expired by at the age of 4 years by severe pneumonia and subsequent respiratory failure. Family 2 A 2-year-old male child, first born to consanguineous parents, presented at the age of 7 months by delayed sitting.
The patient received active vitamin D and oral calcium with no improvement. Mother noticed polyuria, polydipsia, and abdominal enlargement at the age of 1 year; there were no antenatal problems. Marked abdominal distension and hepatomegaly were noted; liver span was 13 cm in the midclavicular line with firm consistency and rounded border. The rest of physical examination was normal. Laboratory examinations revealed reduced serum calcium 7. Lipogram was uneventful.
Serum creatinine was normal. Urinary pH was 5 normal: 4. Bone survey revealed diffuse osteopenia, racketic triad with delayed bone age.
Abdominal ultrasound revealed hepatomegaly with diffuse fatty infiltration and both kidneys enlarged. Liver biopsy showed massive panacinar macrovesicular steatosis with portal tract expansion by fibrosis. At age of 2 years, serum calcium, phosphate, and alkaline phosphatase levels were in normal ranges, yet there was no improvement in growth retardation or other specific features of FBS.
Patients and Methods Genomic DNA was extracted from peripheral blood leukocyte samples withdrawn from all available family members both affected and healthy and was done using the DNA purification Capture Column Kit Gentra kit. The new mutant forms had been detected in the following DNA stretches: for the first family, on direct sequencing of exon 3 including flanking introns of SLC2A2 Glut2 gene , however; for the second family, on direct sequencing of exon 6 including flanking introns of SLC2A2 Glut2 gene.
However, individuals , , , , , , and were heterozygous, for c. Genotyping of family 1 is shown in pedigree Figure 2.
Figure 2: Pedigree of family 1 showing the genotyping of all individuals regarding c. For family 2 , in intron5 of SLC2A2, a G-to-C substitution at position-1 of the splicing acceptor site was found in a homozygous pattern c.
However, individuals , , , , and were heterozygous for c. Genotyping of family 2 is shown in pedigree Figure 4.
Figure 3: Sequencing of intron5 of SLC2A2 for family two showed: a For patient, there is G-to-C substitution at position-1 of the splicing acceptor site in a homozygous pattern c. Figure 4: Pedigree of family 2 showing the genotyping of all individuals regarding c.
Discussion FBS is a rare but distinct clinical entity due to mutation in GLUT2 gene; recently many mutations had been described in both patients homozygous or double heterozygous and first-degree relatives sibs and parents ; about half of the newly diagnosed cases are due to novel mutation [ 2 , 6 ].
Difficulty in molecular diagnosis of FBS is that none of the reported mutations is particularly more frequent, so no specific mutation type could be diagnosed by a simpler molecular technique like ARMS, for example.
Among more than 10 families with RTA occurring in consanguineous mating, we have screened two families coping with the clinical diagnosis of FBS; specific mutation in each family was discovered adding a new information to literature and confirming the idea that mutant types in this gene could be unlimited. Therefore, this molecular analysis has to be extended to many other families to survey the most frequent mutant forms among such disease in order to make diagnosis in the future families using screening molecular tests.
References R. Santer, R. Schneppenheim, D. Suter, J. Schaub, and B. Santer, B.
Steinmann, and J. Sakamoto, E. Ogawa, T. Ohura et al.
Schneppenheim, A. Dombrowski, H. Santer, S. Groth, M. Kinner et al.
Saltik-Temizel, T. Ozer, N. Aksu, E.Of these patients, 12 were Turkish and all had a different mutation [ 6 ]. Steinmann, and J.
FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. Difficulty in molecular diagnosis of FBS is that none of the reported mutations is particularly more frequent, so no specific mutation type could be diagnosed by a simpler molecular technique like ARMS, for example.
A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS. Healthcare Resources To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Santer, B.