Inherited disorders of carbohydrate metabolism

Czech version

Authors: Honzík Tomáš; Zeman Jiří
Authors‘ workplace: Klinika pediatrie a dědičných poruch metabolismu 1. lékařské fakulty Univerzity Karlovy a Všeobecné fakultní nemocnice v Praze
Published in: Čes-slov Pediat 2023; 78 (3): 141-154.
Category: Chapters for Specialization in Pediatrics
doi: https://doi.org/10.55095/CSPediatrie2023/019

Overview

Introduction: Inherited metabolic disorders (IMD) of carbohydrates represent a heterogeneous group of >250 different diseases caused by impaired synthesis, transport or degradation of galactose, fructose, glucose, disaccharides, glycogen, glycosaminoglycans and glycoproteins/glycolipids. Individual IMD of carbohydrates are rare, but the overall incidence in the population is >1:5 000. Their diagnosis, except galactosemia in some countries is not part of laboratory neonatal screening of IMD and depends on clinical suspicion, biochemical and haematological analyses, and indication of selective metabolic screening.

Material and methods: We summarize our experiences with the clinical, diagnostic, and therapeutic aspects of the most common IMD of carbohydrates in >360 patients diagnosed at our institution.

Results: Clinical manifestations in children with IMD of carbohydrates are heterogeneous and may overlap with several diseases. The first symptoms of IMD of galactose and fructose begin with acute manifestations of liver failure with impaired renal tubular functions and Fanconi syndrome. Most liver glycogenoses (GSD) begin with hepatomegaly, growth failure, attacks of hypoglycaemia after 2.5-3 hours of fasting, hepatopathy, dyslipidaemia and lactic acidosis, but also neutropenia (GSD Ib) or liver failure (GSD IV). Muscle glycogenoses are presented by hypotonia and cardiomyopathy (GSD II) and muscle weakness and myalgia with attacks of rhabdomyolysis (GSD V). Hepatic and muscle GSD phenotype overlaps with phosphoglucomutase 1 deficiency. Glucose-galactose transport (GLUT2) disorder links GSD phenotype to nephropathy with Fanconi syndrome. IMD of carbohydrates in complex molecules cause mucopolysaccharidoses (MPS) and congenital disorders of glycosylation (CDG). Clinically characteristic of the MPS and CDG group are craniofacial dysmorphy, encephalopathy, hepato/splenomegaly, growth disorder, bone deformities, involvement of the myocardium and heart valves, hernia, recurrent otitis, and chronic rhinitis.

Conclusion: Early diagnosis is essential for successful treatment. Dietary intervention includes a lactose-free and low-galactose diet (galactosemia), a low-fructose diet (fructose intolerance), an anti-hypoglycaemic regimen with the addition of uncooked starches (liver GSDs), increased protein intake (GSD III), or a ketogenic diet (GLUT1). Some congenital disorders of glycosylation (CDG) can be treated with mannose or galactose. Enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation are used in the treatment of children with MPS.

Keywords:

mucopolysaccharidoses – inherited disorders of carbohydrate metabolism – galactosemia – hereditary fructose intolerance – glycogenoses – congenital disorders of glycosylation

Sources

1. Ferreira CR, Rahman S, Keller M, et al. An international classification of inherited metabolic disorders (ICIMD). J Inherit Metab Dis 2021; 44(1): 164–177.

2. Honzík T, Kožich V, Pešková K, et al. Laboratorní novorozenecký screening. Ces-slov Pediat 2022; 77(1): 12–18.

3. Welling L, Bernstein LE, Berry GT, et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow- up. J Inherit Metab Dis 2017; 40(2): 171–176.

4. Honzík T, Zeman J. Výživa u dědičných metabolických poruch. In: Kohout P, et al. Klinická výživa. Praha: Galén 2021: 779–798.

5. Steinmann B, Santer R. Disorders of fructose metabolism. In: Saudubray JM, Baumgartner MR, García-Cazorla A, et al. Inborn metabolic diseases: diagnosis and treatment. 7^th ed. Heidelberg: Springer 2022: 327–336.

6. Honzík T, Zeman J, et al. Dědičné poruchy metabolismu v kazuistikách. Praha: Mladá fronta, 2016.

7. Walter JH, Labrune P, Laforet P. The glycogen storage diseases and related disorders. In: Saudubray JM, Baumgartner MR, García-Cazorla A, et al. Inborn metabolic diseases: diagnosis and treatment. 7^th ed. Heidelberg: Springer 2022: 179–200.

8. Grünert SC, Elling R, Maag B, et al. Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib. Orphanet J Rare Dis 2020; 15(1): 218.

9. Rossi A, Hoogeveen IJ, Bastek VB, et al. Dietary lipids in glycogen storage disease type III: A systemic literature study, case studies, and future recommendations. J Inherit Metab Dis 2020; 43(4): 770–777.

10. Kolářová H, Ješina P. Metabolické myopatie. Neurologie pro praxi 2022; 23(1): 24–32.

11. Semplicini C, De Antonio M, Taouagh N, et al. Long-term benefit of enzyme replacement therapy with alglucosidase alfa in adults with Pompe disease: prospective analysis from the French Pompe Registry. J Inherit Metab Dis 2020; 43(6): 1219–1231.

12. Santer R, Klepper J. Disorders of glucose and monocarboxylate transporters. In: Saudubray JM, Baumgartner MR, García-Cazorla A, et al. Inborn metabolic diseases: diagnosis and treatment. 7^th ed. Heidelberg: Springer, 2022: 228–230.

13. Jones S, Wijburg FA. Glykosaminoglycans and oligosaccharides disorders: glycosaminoglycans synthesis defects, mucopolosaccharidoses, oligosaccharidoses and sialic acid disorderes. In: Saudubray JM, Baumgartner MR, García-Cazorla A, et al. Inborn metabolic diseases: diagnosis and treatment. 7th ed. Heidelberg: Springer, 2022: 766–777.

14. Murgasova L, Jurovcik M, Jesina P, et al. Otorhinolaryngological manifestations in 61 patients with mucopolysaccharidosis. In J Pediatr Otorhinolaryngol 2020; 135: 110137.

15. Formánková R, Říha P, Keslová P, et al. Transplantace kmenových buněk krvetvorby u dětí s dědičnými metabolickými poruchami a maligní infantilní osteopetrózou. Ces-slov Pediat 2022; 77(5): 276–283.

16. Dvorakova L, Vlaskova H, Sarajlija A, et al. Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II. Clin Genet 2017; 91(5): 787–796.

17. Jaeken J, Morava E. Congenital disorders of glycosylation, dolichol and glycosylphosphatidylinositol metabolism. In: Saudubray JM, Baumgartner MR, García-Cazorla A, et al. Inborn metabolic diseases: diagnosis and treatment. 7^th ed. Heidelberg: Springer, 2022: 811–832.

18. Ondruskova N, Cechova A, Hansikova H. Congenital disorders of glycosylation: Still „hot“ in 2020. Biochim Biophys Acta Gen Subj 2021; 1865(1): 129751.

19. Altassan R, Péanne R, Jaeken J, et al. International guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: diagnosis, treatment and follow up. J Inherit Metab Dis 2019; 42(1): 5–28.

20. Čechová A, Ondrušková N, Tesařová M, et al. Deficit fosfomanomutázy 2: klinická, biochemická a molekulárně-genetická charakteristika 22 pacientů diagnostikovaných v České republice. Ces-slov Pediat 2018; 73(6): 365– 374.

21. Čechová A, Altassan R, Borgel D, et al. Consensus guidelines for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation. J Inherit Metab Dis 2020; 43(4): 671–693.

22. Altassan R, Radenkovic S, Edmondson AC, et al. International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): diagnosis, follow up, and management. J Inherit Metab Dis 2021; 44(1): 148–163.