Fanconi â€“ Bickel Syndrome â€“ two cases report - edigraphic.com

Annals 

of 

Hepatology 

Abstract 

Annals N of Sotelo Hepatology et al. Fanconi 2008; 7(2): – Bickel April-June: Syndrome163-167 163 

Case Report 

Fanconi – Bickel Syndrome – two cases report 

Norberto Sotelo; 1 Ramiro García; 2 René Tostado; 3 Nagasharmila Dhanakotti 4 

A one year eight month old male child and his nine 

month old female sibling were presented with Growth 

retardation, abdominal distension, doll-like faces, 

hepatomegaly, phosphaturia, proximal renal tubular 

dysfunction. The elder sibling also presented with glucosuria, 

hyperglycemia, hypoinsulinemia. The younger 

one later presented with galactosemia. Biopsy of liver 

on these two patients revealed the accumulation of 

glycogen in hepatocytes. 

Key words: Fanconi- Bickel syndrome, glucosuria, 

phosphaturia, glycogenosis. 

Introduction 

FBS is known from 1949 as Hepato Renal glycogenosis, 

with proximal renal tubular alteration characterized 

by glucosuria. Within the classification of glycogenosis 

FBS is denominated as type XI. From the description 

made by Fanconi, 1 until now a little more than 100 cases 

were published in the world literature. 2 

An Autosomal Recessive Disease due to an enzymatic 

defect which has been not yet identified. A pathogenic 

mutation in GLUT- 2 gene of hepatocytes, β cells of pancreas 

and renal tubules, was discovered in 1997. This disorder 

is characterized by growth retardation, rickets, 

hepatomegaly due to hepatic accumulation of glycogen, 

may also present as fasting ketotic hypoglycemia, followed 

by postprandial hyperglycemia, during this stage 

there is also hypoinsulinism due to the altered sensitivity 

of β cells of pancreas to glucose. Due to the consequence 

of proximal renal tubular dysfunction, they also 

present hypophosphatemia and rickets. 2 

1 Head of the Department of Pediatric Internal Medicine. 

2 Head of the Department of Pediatric Nephrology. 

3 Medical Pediatric Resident. 

4 Associated to Department of Pediatric Internal Medicine. 

From the Hospital Infantil del Estado de Sonora, México 

Address for correspondence: 

Norberto Sotelo 

norbertosotelo5@hotmail.com and nsotelo51@gmail.com 

Manuscript received and accepted: 15 February and 24 March 

2008 

Case report 

Case 1 

www.medigraphic.com 

Artemisa 

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A one year eight month old male child who is first 

born of non consanguineous parents of 21 year old both, 

native of Caborca, Sonora. Parents are apparently 

healthy. However, maternal grandmother family has consanguinity. 

This child is a product of first conception, during 

which the mother had regular antenatal visit and did not 

have any antenatal problem. Born of normal delivery, 

cried and respired spontaneously with birth weight of 

3,600 g and discharged along with the mother, was not 

breast fed. Feeding was started with formula feeds, maintained 

with the same, until one year of age. Complimentary 

feeds started since 6 months of age with cereals and 

baby food. Development: Head control at 5th month, sitting 

with support and attempted to crawl from the age of 

8th month. Child yet to walk. 

At one year of age, the child presented with growth retardation, 

abdominal distension, doll- like face and 

hepatomegaly. Laboratory investigation showed Fasting 

hypoglycemia followed by postprandial hyperglycemia. 

Liver function tests were normal. 

Ultrasonography of abdomen revealed hepatomegaly 

without any diffuse parenchymal abnormality. Liver 

biopsy was made, reported as large hepatocytes with 

clear cytoplasm, ballooning and positive for PAS 

staining, characteristic of glycogenosis (Figure 1). 

Hence the diagnosis of Von-Gierke disease was made 

and advice was made regarding feeding frequency and 

corn starch feeds. 

At the age of one year seven month, was presented 

with respiratory distress, the Silverman Anderson score 

of 3, signs of acidosis, pallor, diaphoresis, tachypnea and 

tachycardia, hence the child got hospitalized. The labo- 

ratory examination showed leucocytosis with shift to 

left. There was hyperglycemia. The Gasometry was reported 

as metabolic acidosis (P H 7.10, PCO 2 11, PO 2 108, 

HCO 3 3.4, Base deficit 23.8, S O 2 96.5), on repeated gasometry 

also, the similar reports were obtained. X- ray of 

thorax demonstrated pulmonary condensation. Clinical 

condition continued to detoriate, mandating elective intubation 

and ventilatory support at Pediatric Intensive 

Care Unit. More than the treatment of antibiotics Penicillin 

and Aminoglycoside, Metabolic acidosis was treated

164 

Case 1 

Case 2 

with continuous bicarbonate infusion calculated as per 

acid base deficit depending upon the gasometry. Due to 

persistent hyperglycemia, determination of C peptide 

level was requested, with result of 0.3 ng/mL, with reference 

value of 1.1- 5.0 ng/mL; Insulin level < 0.200μU/L 

with reference value of 5.0- 25μU/L. The antibiotic 

scheme was modified, started on Dicloxacillin, Cefotaxim 

and Fluconazole as Urine culture was positive for 

Candida Albicans of 100,000/HPF. With this, the child 

improved clinically, radiologically and values of laboratory 

examination, hence extubated and transferred to us 

for continued evaluation and treatment. 

The physical examination showed, Head circumfer- 

ence of 48 cm ( 50th centile for age), length of 73 c (< 

5th centile for age), weight of 11,100 g (< 25th centile 

for age); Doll-like face was more prominent, small thorax 

and rachitic changes noted in the costal cartilage. Distended 

abdomen with hepatomegaly of 6 x 5 x 5 cm 

(Figure 2), with genitals relevant to his age and sex also 

noted. Rest of the systemic examination was normal. 

Repeat Gasometry, C peptide, Insulin were requested 

and were continued to be below the normal values 

(metabolic acidosis, 0.3 ng/mL and 1.3μU/L respec- 

Annals of Hepatology 7(2) 2008: 163-167 

A B 

A B 

Figure 1. Liver tissue of Case 1 and Case 2: (A) PAS staining demonstrating glycogen accumulation and (B) Photograph of positive diastase 

test. 


tively). Hence, the possibility of FBS associated with 

glycogenosis was considered. Due to persistent acidosis, 

Nephrology and Genetic opinion was sought. 

Serum and urinary electrolytes of 24 hours were repeated. 

While analyzing Phosphaturia, Negative anion 

gap curve of Hyperchloremic type was observed, 

this was compatible with tubulopathies (Figure 3 

and Table I). 

Radiography of long bones showed evidence of rickets. 

Ultrasonography of Abdomen showed hepatomegaly 

without diffuse hepatic parenchymal lesions. Kidneys, 

Pancreas and Spleen were normal in shape and size. 

In the beginning, the diagnosis of type I glycogenosis 

Von Gierke Disease was considered in this patient. How- 

ever, during the course of evolution, the patient presented 

with metabolic acidosis, due to renal tubular dysfunction, 

pre-prandial hypoglycemia with ketosis followed 

by postprandial elevated blood glucose , associated decreased 

Insulin and C Peptide levels, but at the same time 

not following the clinical course of type I diabetes too. 

After the biochemical analysis and renal functional test 

to demonstrate the proximal renal tubular dysfunction, 

with the results of glucosuria, phosphaturia, bicarbonate

Figure 2. Case 1 showing typical Doll-like face and hepatomegaly 

(marked by lines). 

Table I. Laboratory test. 

loss, hypoglycemia, hypophosphatemia, hypocalcemia, 

hypoglycemia with radiological evidence of rickets, the 

diagnosis of FBS was made in this case as regard to the 

clinical picture. 

The treatment was started with 25 hydroxy Vitamin 

D (0.25μg/24 h or 2,000 MI/kg/24), Disodium phosphate 

with Phosphoric acid as 85% (58.5 g in 1,200 

mL of normal water) 5 times a day and Bicarbonate of 

15 mEq/k/24 h. Dietary advice was made as mater- 

N Sotelo et al. Fanconi – Bickel Syndrome 165 

Anion Gap 


50 

40 

30 

20 

10 

0 

2 

0 10 20 30 40 50 60 

Proportion of urinary chloride 

Figure 3. Demonstrating the displacement of anion gap curve 

towards left (hyperchloremic) in proportion to urinary chloride 

(1- Case 1; 2 – Case 2). AG = urinary Na + urinary K – urinary Cl 

(Case 1: 87 + 14 = 101-57 = +44; Case 2: 32 + 23 = 52-23 = 

+32). 

Blood/Serum Urine 

Reference 

Parameter Case 1 Case 2 Reference value Parameter Case 1 Case 2 value 

Arterial blood P H 7.10 7.33 7.35 – 7.45 Sodium (mEq/L) 87 32 85 – 250 

Sodium (mEq/L) 142 131 135 – 145 Potasium (mEq/L) 14 23 2.5 - 125 

Potassium (mEq/L) 3.9 3.9 3.5 – 5.0 Chloride (mEq/L) 57 23 15 - 40 

Chloride (mEq/L) 110 98 95 – 105 Phosphorous (mg/dL) 28.4 23 0.6 – 1.5 

Bicarbonate (mEq/L) 9 9.3 22 – 26 Glucose (mg/dL) 1,000 Negative Negative 

Calcium (mg/dL) 9 8.9 8.8 – 9.5 Ketone(Mm/dL) 150 Negative or Neg 

Phosphorous (mg/dL) 2.3 2.2 4.0 – 7.0 Amino acid Negative Negative Negative 

Urea (mg/dL) 11 14 15 – 40 Chromatography 

Creatinine (mg/dL) 0.4 0.1 0.6 – 1.2 

Glucose (mg/dL) 117 117 70 - 110 

Uric acid (mg/dL) 1.5 – 2.0 – 2.7 

Alkaline phosphatase IU 14 12 30 – 120 

Cholesterol (mg/dL) 125 139 < 200 

Trigliceride (mg/dL) 370 215 85 – 150 

Insulin (uU/L) 0.20 1.9 5.0 – 25 

C Peptide (ng/mL) 0.3 0.41 1.1 – 5.0 

Alanin amino tranferase U/L 51.0 37.0 0-38.0 

Asparte amino transferase U/L 37.0 28.0 7- 41 

Prothrombin time (sec) 14 .0 13.0 11 – 14 

Thrombo plastin time (sec) 24 .0 21.0 20 – 40 

Total Bilirubin (mg/dL) 0.7 1.4 0-1.1 

Direct Bilirubin (mg/dL) 0.1 0.7 0-0.3 

Unconjugated Bilirubin (mg/dL) 0.6 0.7 0-0.9 

Total protein (g/dL) 7.6 6.8 6-8.7 

Galactose (mg/dL) 4.5 46.8 0-5.0 

nized cow’s milk in the beginning, later whole milk 

was given as the galactose level in the blood was normal. 

In addition to that, fruits, frequent small feeds 

and use of corn starch in the diet of the child also recommended. 

The diet was calculated to provide the calorie 

of 140 kcal/kg of body weight and 5 grams of protein/kg 

of body weight. Regular follow up on outpatient 

basis was advised with Pediatric and Nephrology 

departments. 

1

166 

Case 2 

Eight month old female infant, who is born of second 

conception (sibling of case 1), delivered via naturalis 

with birth weight of 2,500 g, length of 48 cm and head 

circumference of 32 cm. During the neonatal period, was 

hospitalized for transient tachypnea, transient unconjugated 

hyperbilirubinemia and hypoglycemia not associated 

with seizures. The newborn metabolic screening was 

negative, however the estimation of blood galactose level 

later reported to be elevated. 

At the age of 7 month, infant was brought to hospital 

for delay attaining age appropriate milestones (not attained 

head control, not started sitting and crawling). 

The physical examination revealed weight of 7,950 

g, length of 63 cm, which are less for age (3 rd centile), 

Doll-like face, prominent abdomen and hepatomegaly 

Figure 4. Case 2 exhibits Doll-like face and hepatomegaly (marked 

by lines). 

Case 1 

Annals of Hepatology 7(2) 2008: 163-167 


of about 6 cm below the right costal margin (Figure 4). 

Because of these finding, FBS was suspected and the 

following laboratory analysis were requested: Arterial 

blood gas, Serum and Urinary Electrolytes, calcium, 

phosphorous, cholesterol, triglyceride, ultra sonogram 

of abdomen and x-ray of thorax and long bone. They 

were reported as metabolic acidosis (Table I), rickets 

and hepatomegaly devoid of any specific ultrasonographic 

pattern. Based on these results, liver biopsy was 

done and revealed histopathological changes typical of 

glycogenosis (Figure 1). Hence, the suspicion of FBS 

was confirmed and treatment was continued with phosphate 

and bicarbonate replacement. The dietary advice 

was given based on the calculation of 140 kcal/kg of 

body weight, protein of 4.5 gm/kg of body weight in 

the form of maternized cow’s milk, formula of soya, puree 

of fruits and vegetables. 

Discussion 

FBS is a rare clinical entity and rare presentation with 

in the same family affecting the infants between the ages 

of 2 month to 1 year of life. The clinical picture, which is 

noticed in majority of the patients, is characteristic faces 

«Moon- shaped» face or «Doll- like» face. In addition, 

short stature, rickets, protuberant abdomen, and 

hepatomegaly 3-5 are associated features in FBS. In addition, 

biochemical changes encountered as a consequence 

of the altered Proximal Renal Tubular function (glucosuria, 

phosphaturia, bicarbonate loss and hypophosphatemia, 

aminoaciduria). Preprandial ketotic hypoglycemia 

and significant post prandial hyperglycemia and 

hypergalactesemia are noted due to low hepatic uptake. 

There is also hypoinsulinemia due to altered sensitivity 

of β cells of Pancreas to glucose, associated with reduced 

release of monosachroide by hepatic cells during fasting 

Case 2 

Figure 5. Percutaneous liver biopsy of Case 1 and Case 2 (HE 40x) showed large and ballooned hepatocytes with clear cytoplasm.

and intra cellular accumulation with inhibition of glycogenolysis 

leading on to glycogen accumulation and 

hepatomegaly. 

ESTE DOCUMENTO ES ELABORADO POR MEDI- 

GRAPHIC 

6,7 

During the period of fasting, there is reduced blood 

glucose level which is generally not associated with convulsions. 

This hypoglycemia is accompanied by ketosis 

followed by postprandial hyperglycemia, making to consider 

the possibility of ketosis to have a neuro protective 

effect. 2,8 It is also possible to encounter elevation of cholesterol 

and triglyceride in these patients due to accumulation 

of secondary metabolite. 6,7 

With respect to recent discovery in Genetic aspect of 

the disease, mutations in GLUT-2 gene was detected in 

34 cases. 7,9,10 Parental consanguinity was observed in 2/ 

3rd of these patients. Some of these cases were identified 

through Neonatal Screening for Galactosemia. This gene 

is localized much in hepatocytes like in the β cells of 

pancreas, enterocytes and renal tubules. 2 

There is no specific treatment exist for this disease 

in the therapeutic form, besides intravenous hydrations, 

to provide with Vitamin D in the form of 1, 25 

dihydroxy Vitamin D3. Citrate up to 15 mEq/kg/day 

given every 4th hourly to maintain bicarbonate more 

than 20 mEq/dL, phosphate solution orally; to offer 

with fructose and corn starch to provide glucose in 

slow release form and also which do not require diseased 

metabolic pathway. Because of the possible association 

of Galactosemia with FBS, it is recommend- 

N Sotelo et al. Fanconi – Bickel Syndrome 167 


ed to provide the diet free of Galactose, until the results 

of metabolic studies are known. 2,6,10 

References 

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(Aminosaeurediabetes oder nephrotischglukourischer 

Zwergwuchs) bei der Glykogenoseund der Cystinkrankheit. Helv 

Pediat Acta 1949; 4: 359-396. 

2. Pascual JM. Hereditary syndrome of glucose transport. Med Clin 

(Barc.) 2006; 127(18): 709-714. 

3. Garty R, Cooper M, Taibachnik E. The Fanconi syndrome associated 

with hepatic glycogenosis and abnormal metabolism of 

galactose. J Pediatr 1974; 85: 821-823. 

4. Velasquez JL. Síndrome de Fanconi. Bol Med Hosp Infant Mex 

1987; 44: 509-510. 

5. Santer R, Schneppenheim R, Suter D, Schanb J, Steinman B. 

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Bickel. Bol Med Hosp Infant Mex 1991; 48: 255-259. 

7. Santer R, Steinmann B, Schaub J. Fanconi-Bickel syndrome a 

congenital defect of facilitative glucose transport. Curr Mol Med 

2002; 2: 213-227. 

8. De Vivo D, Lackie M, Ferrendelli J, McDougal D. Chronic ketosis 

and cerebral metabolism. Ann Neurol 1987; 3: 331-337. 

9. Sakamoto O, Ogawa E, Ohura T, Igarashi Y, Matsubara Y, 

Narisawa K, et al. Mutation analysis of the GLUT 2 gene in 

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Indian Pediatrics 2007; 44: 223-225.

Fanconi â€“ Bickel Syndrome â€“ two cases report - edigraphic.com

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