HEPATIC GLYCOGENOSIS IN CHILDREN: SPECTRUM OF PRESENTATION AND DIAGNOSTIC MODALITIES
AbstractBackground: Objectives of the study were to determine the clinical spectrum of presentation and various modalities helpful in the diagnosis of liver glycogenosis short of genetic analysis. Methods: All patients under 18 years of age presenting to Paediatric Gastroenterology unit of Children's Hospital, Lahore with suspicion of hepatic glycogen storage disease (GSD) were enrolled over a period of 18 months. Demographic profile and various factors under observation were recorded. Collected data was analysed using SPSS version 22. Results: Among 89 enrolled patients F:M ratio was (1.28:1). The most common GSD was type I (71, 79.7%) followed by III (13, 14.6%), II (3, 3.3%), IV (1, 1.1%) and IX (1, 1.1%). The Abdominal distension was the most common presentation in 89.5% followed by hepatomegaly in 86.5%, diarrhoea in 41.6%, doll’s like appearance in 31.5% and vomiting, acidotic breathing with convulsions in about 20% of children in GSD I. Hepatomegaly (100%), failure to thrive (85%), developmental delay (69%) and splenomegaly (92.3%) were leading presentation in GSD III. Elevated triglycerides (77.5%) followed by transaminesemia (56%), hypercholesterolemia (63%), hyperuricemia (32%) and hypoglycaemia (14%) were significant biochemical findings in GSD I. Consistently raised liver enzymes (92%) and creatinine phosphokinase (100%) in addition to hypertriglyceridemia (69%) were seen in GSD III. The presence of enlarged hepatocytes with clearing of cells favour GSD1 showed in 79% of children while fibrosis and steatosis usually seen in GSD-III (14.6%). Conclusion: Hepatic glycogen storage diseases are serious health issues and should be excluded in any patient who present with hepatomegaly, short stature and hyperlipidaemia to decrease the disease mortality and morbidity.Keywords: glycogen storage disease; children; presentation
Ozen H. Glycogen Storage Diseases: New Perspective. World J Gastroenterol 2007; 13(18):2541–53.
Priya S, Kishnami, Chen YT. Glycogen Storage Diseases In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson text book of pediatrics. 18th ed. Philadelphia: WB Saunders, 2008; p.601– 910.
Mayatepak E, Hoffmann B, Meissner T. Inborn error of carbohydrate metabolism. Best Pract Res Chlin Gastroentrol 2010;24(5);607–18.
Van der beek NA, Hagemans ML, van der Ploeq AT, Reuser AJ, van Doorn PA. Pompe Disease (Glycogen storage disease type-II): clinical features and enzyme replacement therapy. Acta Neurol Belg 2006;106(2):82–6.
Shin YS. Glycogen Storage Disease: clinical, biochemical and molecular heterogeneity. Semin Pediatr Neurol 2006;13(2);115–20.
Beauchamp NJ, Dalton A, Ramaswami U, Niinikoski H, Mention K, Kenny P, et al. Glycogen Storage Disease type-IX: high variability in clinical phenotype. Mol Genet Metab 2007;92(1-2):88–99.
Bali DS, Chen YT, Austin S, Goldstein JL. Glycogen Storage Disease Type I. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, et al., editors. Gene Reviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2018 Oct 30]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1312/
Lyer SG, Chen Cl, Wang CC, Wang SH, Concejero AM, Liu YW, et al. long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl 2007;13(6):848–52.
Saltik IN, Ozen H, Ciliv G, Kocak N, Yuce A, Gurakan F, et al. Glycogen Storage Disease type Ia: frequency and clinical course in Turkish Children. Indian J Pediatr 2000;67(7):497–501.
Moraru E, Cuvinciuc O, Antonesei L, Mihaila D, Bozomitu L, Rusu T, et al. Glycogen Storage Disease Type-I between Chronic Ambulatory Follow-up and Pediatric Emergency. J Gastrointestin Liver Dis 2007;16(1):47–51.
Schoser B, Hill V, Raben N. Therapeutic approaches in Glycogen Storage Disease type II/Pompe Disease. Neurotherapeutics 2008;5(4):569–78.
Ahmed A, Qasim G, Rehman A, Manan A, Afzal A. Liver biopsy as a diagnostic tool in undiagnosed chronic hepatic problems in children. Pak Paed J 2006;30(1)34–7.
Saeed S, Arshad H, Alvi A, Suleman H. Clinical presentation and biochemical findings in children with Glycogen storage disease type 1A. Pak Armed Forces Med J 2015;65(5):682–85.
Bhattacharya K. Dietary dilemmas in the management of glycogen storage disease type I. J Inherit Metab Dis 2011;34(3):621–9.
Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV. Glomerular and Tubular Function in Glycogen Storage Disease. Pediatr Nephrol 1995;9(6):705–10.
Sentner CP, Caliskan K, Vletter WB, Smit GP. Heart Failure Due to Severe Hypertrophic Cardiomyopathy Reversed by Low Calorie, High Protein Dietary Adjustments in a Glycogen Storage Disease Type IIIa Patient. JIMD Rep 2012;5:13–6.
Bali DS, Goldstein JL, Fredrickson K, Rehder C, Bonery A, Austin S, et al. Variability of disease spectrum in children with liver phosphorylase kinase deficiency caused by mutations in the PHKG2 gene. Mol Genet Metab 2014;111(3):309–13.
Roscher A, Patel J, Hewson S, Nagy L, Feigenbaum A, Kronick J, et al. The natural history of glycogen storage disease types VI and IX: Long-term outcome from the largest metabolic center in Canada. Mol Genet Metab 2014;113(3):171–6.
Chen YT, Cornblath M, Sidbury JB. Cornstarch Therapy in Type I Glycogen-Storage Disease. N Engl J Med 1984;310(3):171–5.