Clinical Characteristics of Children with Fanconi-Bickel Syndrome
0
Citation
0
Reference
20
Related Paper
Abstract:
[Objective] To provide a descriptive analysis of Fanconi-Bickel syndrome(FBS),which is a rare inherited disease caused by mutations in the glucose transporter 2(GLUT2) gene and is not well characterized in China.[Methods] We reported the first two cases of FBS in China and described the clinical characteristics of FBS by combining our results with a review of the literatures.[Results] Both of the two affected children who were confirmed by genetic analysis of GLUT2 gene presented with manifestations similar to Glycogen Storage Disease Type 1(GSD-I),severe short stature,hypoglycemia,hepatomegaly secondary to glycogen accumulation.However,post prandial hyperglycemia,glycosuria and hypophosphatemic rickets secondary to proximal renal tubular dysfunction,type II renal acidosis without elevated lactic acid and uric acid in FBS do not developed in GSD-I.As the characteristics of being born as small for gestational age and apparent liver dysfunction in our children have been seldom described in the literatures,the present study will supplement the up-to-date clinical characteristic spectrum for FBS.[Conclusions] FBS should be differentiated from GSD-I and diabetes mellitus.Careful medical history collection,physical examination,laboratory data evaluation,imaging studies and liver biopsy are helpful in making the correct diagnosis.Keywords:
GLUT2
Glycosuria
Fanconi syndrome
Cite
GLUT2
Failure to Thrive
Hypophosphatemic Rickets
Hypophosphatasia
Cite
Citations (46)
Şeker-Yılmaz B, Kör D, Bulut FD, Yüksel B, Karabay-Bayazıt A, Topaloğlu AK, Ceylaner G, Önenli-Mungan N. Impaired glucose tolerance in Fanconi-Bickel syndrome: Eight patients with two novel mutations. Turk J Pediatr 2017; 59: 434-441. Fanconi-Bickel syndrome (FBS) is a rare, autosomal recessive disorder of carbohydrate metabolism caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene. Prominent findings are failure to thrive, renal tubular acidosis, hypoglycemia and postprandial hyperglycemia even mimicking diabetes mellitus. Eight patients from 6 families with FBS were included in this study. c.482_483insC homozygous mutation was detected in six patients from four different families. Mutation analysis of SLC2A2 gene revealed two novel homozygous mutations; c.1069delGinsAATAA and c.575A > G. Standard oral glucose tolerance test with 1.75 g/kg oral glucose was performed in six of the patients who were older than 3-years of age. Impaired glucose tolerance was found in all patients as expected and two of them had overt diabetes. None of the antidiabetic medications were given to them in order to avoid significant hypoglycemia. Beside the conservative treatment, follow up with frequent oral glucose tolerance tests are planned. We report these cases of FBS, as GSD XI is rare, two novel mutations were detected and also to highlight the risk of diabetes mellitus; although there is not a consensus about the treatment.
Failure to Thrive
Fanconi syndrome
GLUT2
Glucose tolerance test
Cite
Citations (11)
Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare type of glycogen storage disease (GSD). It is caused by homozygous or compound heterozygous mutations within GLUT2, the gene encoding the most important facilitative glucose transporter in hepatocytes, pancreatic b-cells, enterocytes, and renal tubular cells. To date, 112 patients have been reported in the literature. Most patients have the typical combination of clinical symptoms: hepatomegaly secondary to glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy, and severely stunted growth. In 63 patients, mutation analysis has revealed a total of 34 different GLUT2 mutations with none of them being particularly frequent. No specific therapy is available for FBS patients. Symptomatic treatment is directed towards a stabilization of glucose homeostasis and compensation for renal losses of various solutes. In addition to the clinical and molecular genetic aspects of FBS, this review discusses the pathophysiology of the disease and compares it to recent findings in GLUT2 deficient transgenic animals. An overview is also provided on recently discovered members of the rapidly growing family of facilitative glucose transporters, which are novel candidates for congenital disorders of carbohydrate metabolism. Keywords: fanconi-bickel syndrome, facilitative glucose transport, glycogen storage disease, glucose transporter2 (glut2)
GLUT2
Fanconi syndrome
Carbohydrate Metabolism
Cite
Citations (157)
Glycogen synthase deficiency (glycogen storage disease 0 — GSD 0) caused by mutations in the GYS2 gene is characterized by a lack of glycogen synthesis in the liver. It is a rare condition of disturbed glycogen homeostasis in the liver with less than 30 cases reported in the literature so far. We report a 9 year old boy diagnosed with GSD 0 due to the newly identified, highly pathogenic homozygous mutation: NM_021957.3:p.Phe574Leu/c.1720T > C in ex. 14. A random, asymptomatic hypoglycemia with ketonuria was found in this patient at the age of 7. His developmental parameters were within normal ranges. Oral glucose tolerance test showed normal baseline blood levels of glucose, insulin and lactate, and their increase following glucose intake. Eight-hour fasting plasma glucose test, revealed glucose blood level of 34 mg/dl with no clinical symptoms. The results of these tests suggested GSD 0. Molecular analysis of the GYS2 gene was not feasible, but this particular gene was included in the panel of hypoglycemia of whole exome sequencing (WES) which was at our disposal.
Ketonuria
Cite
Citations (19)
The phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in PHKA2, and results in deficiency of the phosphorylase kinase enzyme, particularly in the liver. Like other GSDs, GSD IXɑ2 can present with hypoglycemia and post-prandial lactic acidosis, but has never been reported in a newborn, nor with lactic acidosis as the presenting feature. Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis, renal tubulopathy, and sensorineural hearing loss (SNHL) diagnosed with GSD IXɑ2 through exome sequencing. Review of the literature suggests this case represents an atypical and severe presentation of GSD IXɑ2 and proposes expansion of the phenotype to include neonatal lactic acidosis and renal tubulopathy.
Lactic acidosis
Tubulopathy
Hyperinsulinemic hypoglycemia
Cite
Citations (1)
Failure to Thrive
Fanconi syndrome
Aminoaciduria
Tubulopathy
Enteral administration
Myoglobinuria
Cite
Citations (21)
Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare autosomal recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a member of the facilitative glucose transporter family (Santer et al. J Inherit Metab Dis 21:191–194, 1998). The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal renal tubular dysfunction, rickets and severe short stature. We report 2 Palestinian patients from 2 families who were homozygous for the mutation p.R301X (C>T) in exon 7of GLUT2 gene. Patient 1 showed clinical and laboratory improvement with age characterized by normal growth and resolution of rickets. Patient 2 had severe phenotype characterized by progressive weight loss, persistent metabolic acidosis, marked polyuria and clinical and laboratory findings of rickets progressing to death at age 10 months. This report further expands the clinical spectrum of FBS even with identical mutations. Other yet unknown genetic, environmental or stochastic factors may be responsible for phenotypic variability
GLUT2
Fanconi syndrome
Nephrocalcinosis
Failure to Thrive
Polyuria
Tubulopathy
Cite
Citations (10)
To describe two patients with Fanconi's nephropathy secondary to glycogen storage disease and speculate on the possible etiology.Convenience sample.Tertiary care, referral center.Two related children referred for failure to thrive, rickets, and hepatomegaly.Dietary and therapeutic measures for rickets and renal tubular acidosis.The main laboratory findings were fasting hypoglycemia and massive glucosuria, with evidence of multiple renal tubular dysfunction characteristic of the Fanconi syndrome. Liver and kidney biopsy specimens were consistent with glycogen storage disease. Enzymatic assay of liver homogenates revealed marked deficiency of phosphorylase b kinase in one patient and absent activity in the other.Phosphorylase b kinase deficiency may be causally related to hepatorenal glycogenosis with the Fanconi syndrome. More patients with this syndrome need to be studied before a definitive causal role is implicated.
Fanconi syndrome
Phosphorylase kinase
Hypophosphatemia
Failure to Thrive
Renal tubular acidosis
Aminoaciduria
Cite
Citations (25)
Glycogen storage disease type VI (GSD VI) is an autosomal recessive disorder of glycogen metabolism due to mutations in the glycogen phosphorylase gene (PYGL), resulting in a deficiency of hepatic glycogen phosphorylase. We performed a systematic literature review in order to collect information on the clinical phenotypes and genotypes of all published GSD VI patients and to compare the data to those for GSD IX, a biochemically and clinically very similar disorder caused by a deficiency of phosphorylase kinase. A total of 63 genetically confirmed cases of GSD VI with clinical information were identified (median age: 5.3 years). The age at presentation ranged from 5 weeks to 38 years, with a median of 1.8 years. The main presenting symptoms were hepatomegaly and poor growth, while the most common laboratory findings at initial presentation comprised elevated activity of liver transaminases, hypertriglyceridemia, fasting hypoglycemia and postprandial hyperlactatemia. Liver biopsies (n = 37) showed an increased glycogen content in 89.2%, liver fibrosis in 32.4% and early liver cirrhosis in 10.8% of cases, respectively. No patient received a liver transplant, and one successful pregnancy was reported. Our review demonstrates that GSD VI is a disorder with broad clinical heterogeneity and a small number of patients with a severe phenotype and liver cirrhosis. Neither clinical nor laboratory findings allow for a differentiation between GSD VI and GSD IX. Early biochemical markers of disease severity or clear genotype phenotype correlations are missing. Given the overall benign and unspecific phenotype and the need for enzymatic or genetic analyses for confirmation of the diagnosis, GSD VI is likely underdiagnosed. With new treatment approaches in sight, early, pre-symptomatic diagnosis, especially with respect to hepatic cirrhosis, will become even more important.
Glycogen debranching enzyme
Phosphorylase kinase
Liver disease
Hyperlactatemia
Cite
Citations (13)