A 4.5-year-old boy born of non-consanguineous marriage, presented with gradually progressive abdominal distension since 3 month of age. Polyuria, polydipsia, failure to thrive and progressive lower limb deformity in the form of knock knees was observed since 1.5 years of age. He had undergone deformity correction surgery of genu valgum at 4 years of age and had received 25 lac units of oral cholecalciferol over the past 12 months. There was no history of jaundice, fracture or seizures. He was born at term weighing 2.5 kg, of an uneventful pregnancy. Developmental milestones were normal. Dental eruption started at 20 months. Family history was not significant.

Examination revealed severe retardation of both weight 10.5 kg (Wt SDS: –3.6) and height 80 cm (Ht SDS: –5.8). He had rounded doll-like facies, enamel hypoplasia and features of rickets in form of frontal bossing, wrist widening, rachitic rosary and genu valgum. Systemic examination revealed diffuse, non tender, firm hepatomegaly (liver span 9cm) without splenomegaly. Signs of proximal muscle weakness were present. Quantification of urine output revealed polyuria (urine output 6 mL/kg/hr).

Investigations revealed hyperchloremic (S.Cl-115 mmol/L; normal 96-106) metabolic acidosis (pH-7.38, HCO3-14.1mmol/L, pCO2 24.3), with simultaneous urine pH of 6 and positive urinary anion gap (39). 24-hour urinary calcium was high (17.2 mg/kg/day; normal <4).

Serum creatinine and electrolyte, serum calcium, serum vitamin D (25-OH vitamin D and 25-OH vitamin) were normal. Low serum phosphorus (2.8 mg/dL; normal 4-7) and elevated alkaline phosphatase (673 IU/L; normal 57-180) were found. Other investigations like serum uric acid, SGPT, PT, aPTT, Total serum bilirubin, Total protein, S. Albumin, S. Cholesterol were also normal. Fasting hypoglycemia (blood sugar 28 mg/dL) and post-prandial hyperglycemia (blood sugar 240 mg/dL) was detected on several occasions. Critical sample collected during hypoglycemia (blood sugar 28 mg/dL) revealed normal blood lactate (5 mg/dL; normal 4.5-20), serum ketones (1.2 mg/dL; normal 0.3-2), and serum ammonia (88 U/L; normal 10-90).

Ultrasound abdomen revealed hepatomegaly with bright echotexture. Ophthalmological examination was normal. X-ray wrist showed features of rickets. Liver biopsy did not reveal any glycogen-laden cells.

A diagnosis of FBS was considered and genetic analysis by direct sequencing of DNA revealed a rare homozygous splice site mutation c.16-1G>A or IVS 1-1G>A in GLUT-2 gene. Both parents were carriers.

Child was advised frequent feeds with complex carbohydrate diet, oral sodium bicarbonate (5 mEq/kg/d), potassium (2mEq/kg/day) and phosphate (40 mg/kg/d) supplement. On last follow-up, at 5y 6mo of age, he had gained 2.5 kg in weight (13 kg) and 1.2 cm in height (81.2 cm). Liver span was 9 cm and features of rickets were present. The blood biochemistry was within the normal range, but hypercalciuria was persistent.

The gene GLUT-2 is located on chromosome 3q26.1-q26.3 and encodes glucose transporter protein 2 expressed in hepatocytes, pancreatic beta cells, enterocytes and renal tubular cells. More than 34 different mutations are reported, which provides molecular basis of the disease [2]. Since the first description in 1949, more than 150 cases of FBS have been reported, with three from India [3-5]. Accumulation of glycogen in renal tubular cells causes proximal tubular dysfunction leading to Fanconi nephropathy with variable renal phosphate wasting [6]. Presence of hypercalciuria is rarely reported. Although it is postulated to be due to phosphaturia induced down- regulation of renal tubular 1 alpha-hydroxylase activity, the etiology of hypercalciuria remains uncertain [7].

No specific treatment has been identified. Small frequent feeds and uncooked corn starch at bedtime should be offered to prevent hypoglycemia. Since glucose wasting is very high, adequate calorie supplementation is very essential for normal growth. Long term replacement therapy for proximal tubular losses is needed.

Contributors: SR: Diagnosed and managed the case; RS, RP: literature search and prepared the manuscript; ST, KH: mutation analysis. All authors were involved in preparation of manuscript and approving the final version.

Funding: None; Competing interest: None stated.

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