Background: Glycogen storage disease type 1 (GSD1) is a rare and genetically heterogeneous metabolic defect of gluconeogenesis due to mutations of either the G6PC gene (GSD1a) or the SLC37A4 gene (GSD1b). Osteopenia is a known complication of GSD1. Objectives: The aim of this study was to investigate the effects of poor metabolic control and/or use of GSD1-specific treatments on bone mineral density (BMD) and metabolism in GSD1 patients. Methods: In a multicenter, cross-sectional case-control study, we studied 38 GSD1 (29 GSD1a and 9 GSD1b) patients. Clinical, biochemical and instrumental parameters indicative of bone metabolism were analyzed; BMD was evaluated by dual-emission X-ray absorptiometry and quantitative ultrasound. Results: Both GSD1a and GSD1b patients showed reduced BMD compared with age-matched controls. In GSD1a patients, these abnormalities correlated with compliance to diet and biochemical indicators of metabolic control. In GSD1b patients, BMD correlated with the age at first administration and the duration of granulocyte colony-stimulating factor (G-CSF) therapy. Conclusions: Our data indicate that good metabolic control and compliance with diet are highly recommended to improve bone metabolism in GSD1a patients. GSD1b patients on G-CSF treatment should be carefully monitored for the risk of osteopenia/osteoporosis.

1.
Marcolongo P, Fulceri R, Gamberucci A, Czegle I, Banhegyi G, Benedetti A: Multiple roles of glucose-6-phosphatases in pathophysiology: state of the art and future trends. Biochim Biophys Acta 2012;1830:2608-2618.
2.
Galli L, Orrico A, Marcolongo P, Fulceri R, Burchell A, Melis D, Parini R, Gatti R, Lam C, Benedetti A, Sorrentino V: Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c. FEBS Lett 1999;459:255-258.
3.
Melis D, Fulceri R, Parenti G, Marcolongo P, Gatti R, Parini R, Riva E, della Casa R, Zammarchi E, Andria G, Benedetti A: Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature. Eur J Pediatr 2005;164:501-508.
4.
Rake JP, Visser G, Labrune P, et al: Glycogen storage disease type I: diagnosis, management, clinical course and outcome - results of the European Study on Glycogen Storage Disease type I (ESGSDI). Eur J Ped 2002;161:S20-S34.
5.
Melis D, della Casa R, Parini R, et al: Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b. Eur J Pediatr 2009;168:1069-1074.
6.
Melis D, Parenti G, della Casa R, et al: Crohn's-like ileo-colitis in patients affected by glycogen storage disease Ib: two years' follow-up of patients with a wide spectrum of gastrointestinal signs. Acta Paediatr 2003;92:1415-1421.
7.
Donadieu J, Leblanc T, Bader Meunier B, Barkaoui M, Fenneteau O, Bertrand Y, Maier-Redelsperger M, Micheau M, Stephan JL, Phillipe N, Bordigoni P, Babin-Boilletot A, Bensaid P, Manel AM, Vilmer E, Thuret I, Blanche S, Gluckman E, Fischer A, Mechinaud F, Joly B, Lamy T, Hermine O, Cassinat B, Bellanné-Chantelot C, Chomienne C, French Severe Chronic Neutropenia Study Group: Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia: experience of the French Severe Chronic Neutropenia Study Group. Haematologica 2005;90:45-53.
8.
Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Fier C, Freedman M, Kannourakis G, Kinsey S, Schwinzer B, Zeidler C, Welte K, Dale DC, Severe Chronic Neutropenia International Registry: The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 2006;107:4628-4635.
9.
Melis D, Pivonello R, Parenti G, della Casa R, Salerno M, Lombardi G, Sebastio G, Colao A, Andria G: Increased prevalence of thyroid autoimmunity and hypothyroidism in patients with glycogen storage disease type I. J Pediatr 2007;150:300-305.
10.
Melis D, Pivonello R, Parenti G, della Casa R, Salerno M, Balivo F, Piccolo P, di Somma C, Colao A, Andria G: The GH-IGF axis in glycogen storage disease type 1 (GSD1): evidence of different growth patterns and IGF levels in patients with GDSD1a and GSD1b. J Pediatr 2010;156:663-670.
11.
Lee PJ, Patel JS, Fewtrell M, et al: Bone mineralisation in type 1 glycogen storage disease. Eur J Pediatr 1995;154:483-487.
12.
Rake JP, Visser G, Huismans D, et al: Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study. J Inherit Metab Dis 2003;26:371-384.
13.
Soejima K, Landing BH, Roe TF, Swanson VL: Pathologic studies of the osteoporosis of von Gierke's disease (glycogenosis la). Pediatr Pathol 1985;3:307-319.
14.
Miller TT, Norton KI, Rosh JR: Case report 765: von Gierke's disease. Skeletal Radiol 1993;22:199-202.
15.
Minarich LA, Kirpich A, Fiske LM, Weinstein DA: Bone mineral density in glycogen storage disease type Ia and Ib. Genet Med 2012, E-pub ahead of print.
16.
Soyka LA, Fairfield WP, Klibansky A: Clinical review 117: hormonal determinants and disorders of peak bone mass in children. J Clin Endocrinol Metab 2000;85:3951-3963.
17.
Seino Y: Cytokines and growth factors which regulate bone cell function. Acta Astronaut 1994;33:131-136.
18.
Tramontana J, Benghuzzi H, Tucci M, Tsao A, Hughes J: Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model. Biomed Sci Instrum 2001;37:293-298.
19.
Valerio G, del Puente A, Esposito-del Puente A, Buono P, Mozzillo E, Franzese A: The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res 2002;58:266-272.
20.
Baroncelli GI, Federico G, Bertelloni S, de Terlizzi F, Cadossi R, Saggese G: Bone quality assessment by quantitative ultrasound of proximal phalanxes of the hand in healthy subjects aged 3-21 years. Pediatr Res 2001;49:713-718.
21.
Gimeno Ballester J, Azcona San Julián C, Sierrasesúmaga Ariznabarreta L: Bone mineral density determination by osteosonography in healthy children and adolescents: normal values. An Esp Pediatr 2001;54:540-546.
22.
Inzucchi SE, Robbins RJ: Effects of growth hormone on human bone biology. J Clin Endocrinol Metab 1994;79:691-694.
23.
Krieger NS, Sessler NE, Bushinsky DA: Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 1992;262:F442-F448.
24.
Green J, Kleeman CR: Role of bone in regulation of systemic acid-base balance. Kidney Int 1991;39:9-26.
25.
Kraut JA: The role of metabolic acidosis in the pathogenesis of renal osteodystrophy. Adv Ren Replace Ther 1995;2:40-51.
26.
Christopher MJ, Link DC: Granulocyte colony-stimulating factor induces osteoblast apoptosis and inhibits osteoblast differentiation. J Bone Miner Res 2008;23:1765-1774.
27.
Gluer CC: Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. J Bone Miner Res 1997;8:1280-1288.
28.
Butakova SS, Nozdrachev AD: Effect of calcium-regulating hormones and calcium channel modulators on glucose consumption by muscle and adipose tissues in vivo and in vitro. Bull Exp Biol Med 2009;148:171-174.
29.
Vignolo M, Parodi A, Mascagni A, Torrisi C, de Terlizzi F, Aicardi G: Longitudinal assessment of bone quality by quantitative ultrasonography in children and adolescents. Ultrasound Med Biol 2006;32:1003-1010.
30.
Binkley TL, Berry R, Specker BL: Methods for measurement of pediatric bone. Rev Endocr Metab Disord 2008;9:95-106.
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