Perinatal/Neonatal Case Presentation - Nature

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following institution of diet with frequent small meals and galactose-free- milk as well as pharmacological treatment with phosphate and vitamin a-. OH-D3.
Perinatal/Neonatal Case Presentation The Fanconi–Bickel Syndrome: a Case of Neonatal Onset Silvia Riva, MD Carmela Ghisalberti, MD Rossella Parini, MD Francesca Furlan, MD Alberto Bettinelli, MD Marco Somaschini, MD

A male newborn infant was recognized having Fanconi–Bickel syndrome (FBS) in the neonatal period. The presenting clinical findings were hyperglycemia and polyuria detected during an episode of acute enteritis. Physical examination was normal, biochemical analyses were suggestive of FBS: glycosuria, proteinuria, phosphaturia, generalized aminoaciduria, and increased levels of urinary b2-microglobulin, serum glucose and serum alkaline phosphatase. The molecular genetic analysis showed homozygosity for mutations within the gene of the glucose transporter 2 (Glut 2), 1213 C>T. The patient demonstrated improved clinical and metabolic status following institution of diet with frequent small meals and galactose-freemilk as well as pharmacological treatment with phosphate and vitamin aOH-D3. In conclusion, infants showing hyperglycemia and polyuria may be considered having FBS also in the neonatal period. Early institution of adequate caloric intake and replacement of electrolytes and vitamin D may avoid or reduce metabolic complications. Journal of Perinatology (2004) 24, 322–323. doi:10.1038/sj.jp.7211092

INTRODUCTION The Fanconi–Bickel syndrome (FBS), originally described in 1949, is a rare, well-defined clinical entity that is inherited in an autosomal recessive mode. It is characterized by hepatorenal glycogen accumulation, fasting hypoglycemia as well as postprandial hyperglycemia and hypergalactosemia, proximal renal tubular dysfuction, rickets and markedly stunted growth. The carbohydrate abnormalities indicate impaired utilization of two monosaccharides (glucose and galactose). The activity of enzymes involved in galactose metabolism has repeatedly been found to be normal.1,2 In 1987, Manz et al. postulated a defect of the diffusion

Division of Neonatology (S.R., C.G., M.S.), Ospedale Bolognini, Seriate, Bergamo, Italy; Department of Pediatrics (R.P., F.F.), Istituti Clinici di Perfezionamento, Milano, Italy; and Division of Pediatrics (A.B.), Ospedale di Merate, Italy. Address correspondence and reprint request to Marco Somaschini, MD, Divisione di Neonatologia e Patologia Neonatale, Ospedale Bolognini, 24068 Seriate, Bergamo, Italy.

carrier facilitating influx and efflux of glucose and galactose in liver cells as well as in the basolateral membrane of proximal renal tubule cells. This would lead to high intracellular glucose concentration, inhibition of glycogen degradation and proximal tubular dysfunction.1 The first manifestations of this syndrome are first recognized usually between 3 and 10 months of age when the children present with clinical signs of rickets, short stature (T. Journal of Perinatology 2004; 24:322–323 r 2004 Nature Publishing Group All rights reserved. 0743-8346/04 $25

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Neonatal Fanconi–Bickel Syndrome

DISCUSSION The originality of this case is the timing of diagnosis in the neonatal period because of the early observation of polyuria and hyperglycemia. The incidence of FBS is not known; 109 cases from 88 families have been described worldwide so far.2 To our knowledge, only three other cases of FBS have been reported that were recognized in the neonatal period. One of these was found to have high galactose levels in neonatal screening.3 To confirm the diagnosis, we performed molecular genetic analysis. In 1997, Santer et al. described the basic defect of this disease when reporting homozygosity for mutations within the gene of the glucose transporter 2 (Glut 2) in four patients. These mutations represented the first detection of a congenital defect within a whole family of membrane proteins, the facilitative glucose transporters.2 As in our case, the affected infants are frequently the products of a consanguineus parentage.1 No specific therapy is available for this syndrome; only symptomatic replacement of water, electrolytes, vitamin 1a-OH-D3 and phosphate, restriction of galactose intake, a diabetes mellituslike diet and adequate caloric intake with a frequent small meals may improve growth.4 Without oral phosphate and vitamin D supplementation severe hypophosphatemic rickets may occur in the first months of age. After initiation of frequent small meals and galactose-free-milk diet and pharmacological treatment with

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Silvia et al.

phosphate and vitamin D, our patient had clinical and metabolic improvement. At the age of 1 year his growth, clinical condition and metabolism of vitamin D are normal. Long-term prognosis is not known; in general, there is no progression to glomerular insufficiency1 and no deterioration of tubular defects.3

Acknowledgments We are thankful to R. Santer (Department of Paediatrics, University of Kiel, Germany) for the genetic analyses of glucose transmitter.

References 1. Santer R, Schneppenheim R, Suter D, Schaub J, Steinmann B. Fanconi– Bickel, syndromeFthe original patient and his natural history, historical steps leading to the primary defect, and a review of the literature. Eur J Pediatr 1998;157:783–97. 2. Santer R, Groth S, Kinner M, et al. The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in Patients with Fanconi–Bickel syndrome. Hum Genet 2002;110:21–9. 3. Mu¨ller D, Santer R, Krowinkel M, Christiansen B, Schaub J. Fanconi–Bickel syndrome presenting in neonatal screening for galactosaemia. J Inher Metab Dis 1997;20:607–8. 4. Manz F, Bickel H, Brodehl J, et al. Fanconi–Bickel syndrome. Pediatr Nephrol 1987;1:509–18.

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