Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa
-
Caiqi Du
Abstract
Objectives
To investigate the clinical and genetic characteristics of children with glycogen storage disease type IIIa (GSD IIIa) and to explore the muscle involvement and manifestations of GSD IIIa patients.
Methods
The clinical data of 11 patients with GSD IIIa diagnosed by genetic testing from 2003 to 2019 were retrospectively analyzed.
Results
Twenty variants of AGL gene were detected in 11 patients, eight of which were novel variants. Before treatment, the height was significantly backward. All patients had hepatomegaly. Abnormal biochemical indicators were mainly manifested as significantly increased serum liver and muscle enzymes, accompanied by hypertriglyceridemia, hypoglycemia, hyperlactacidemia, slightly elevated pyruvic acid, and metabolic acidosis. After treatment, the height and liver size of the patients were significantly improved. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), lactic acid and pyruvic acid in children were significantly decreased, while creatine kinase (CK) was significantly increased. During follow-up monitoring, six patients developed ventricular hypertrophy. Lactate dehydrogenase (LDH) (691.67 ± 545.27 vs. 362.20 ± 98.66), lactic acid (3.18 ± 3.05 vs. 1.10 ± 0.40), and pyruvic acid (64.30 ± 39.69 vs. 32.06 ± 4.61) were significantly increased in patients with ventricular hypertrophy compared with those without ventricular hypertrophy.
Conclusions
In clinical cases of upper respiratory tract infection or gastrointestinal symptoms accompanied by hypoglycemia, dyslipidemia, metabolites disorders, elevated serum liver, and muscle enzymes, the possibility of GSD IIIa should be vigilant. During treatment monitoring, if lactic acid, pyruvic acid, LDH, and CK rise, it indicates that the disease is not well controlled and there is the possibility of cardiac hypertrophy.
Funding source: Program for ChangJiang Scholars and Innovative Research Team in University
Award Identifier / Grant number: PCSIRT1131
Acknowledgments
This study was supported by grants from Program for ChangJiang Scholars and Innovative Research Team in University (PCSIRT1131).
Research funding: This study was supported by grants from Program for ChangJiang Scholars and Innovative Research Team in University (PCSIRT1131).
Author contributions: Y.L., D.C.Q., and L.X.P. designed and organized the study. H.W., M.Z., H.M.H., C.Z., and L.Z.G. cared for the patients, acquired the clinical data, and prepared the samples from the family members. Y.L. and D.C.Q. wrote the manuscript that was edited by all other authors. All authors read and approved the final manuscript.
Competing interests: The authors confirm that there is no conflict of interests associated with this manuscript.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study protocol was approved by the Committee on Human Research at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (ethics no. Tj-irb20180703). All study procedures were conducted in accordance with the tenets of the Declaration of Helsinki, and its subsequent amendments.
References
1. Sentner, CP, Hoogeveen, IJ, Weinstein, DA, Santer, R, Murphy, E, McKiernan, PJ, et al. Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome. J Inherit Metab Dis 2016;39:697–704. https://doi.org/10.1007/s10545-016-9932-2.Search in Google Scholar
2. Kishnani, PS, Austin, SL, Arn, P, Bali, DS, Boney, A, Case, LE, et al. Glycogen storage disease type III diagnosis and management guidelines. Genet Med 2010;12:446–63. https://doi.org/10.1097/gim.0b013e3181e655b6.Search in Google Scholar
3. Lu, C, Qiu, Z, Sun, M, Wang, W, Wei, M, Zhang, X. Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations. J Hum Genet 2016;61:641–5. https://doi.org/10.1038/jhg.2016.24.Search in Google Scholar
4. Vidal, P, Pagliarani, S, Colella, P, Costa Verdera, H, Jauze, L, Gjorgjieva, M, et al. Rescue of GSDIII phenotype with gene transfer requires liver- and muscle-targeted GDE expression. Mol Ther 2018;26:890–901. https://doi.org/10.1016/j.ymthe.2017.12.019.Search in Google Scholar
5. Schwenter, F, Ratjen, F, Berk, T, Gallinger, S, Gryfe, R, Gradinger, AB, et al. Juvenile polyposis syndrome, SMAD4 mutations, and hereditary hemorrhagic telangiectasia. J Pediatr Gastroenterol Nutr 2012;54:120–2. https://doi.org/10.1097/mpg.0b013e3182238514.Search in Google Scholar
6. Illingworth, B, Cori, GT. Structure of glycogens and amylopectins. III. Normal and abnormal human glycogen. J Biol Chem 1952 Dec;199:653–60.10.1016/S0021-9258(18)38503-XSearch in Google Scholar
7. Wolfsdorf, JI, Holm, IA, Weinstein, DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am 1999 Dec;28:801–23. https://doi.org/10.1016/s0889-8529(05)70103-1.Search in Google Scholar
8. Shan, J, Wei, W, Min, W, Zheng-qing, Q. Diagnostic value of epinephrine stimulation test in distinguishing type I and type III glycogen storage diseases. Med J Peking Union Med Coll Hosp 2014;5:389–92.Search in Google Scholar
9. Shen, JJ, Chen, YT. Molecular characterization of glycogen storage disease type III. Curr Mol Med 2002;2:167–75. https://doi.org/10.2174/1566524024605752.Search in Google Scholar
10. Lucchiari, S, Donati, MA, Parini, R, Melis, D, Gatti, R, Bresolin, N, et al. Molecular characterisation of GSD III subjects and identification of six novel mutations inAGL. Hum Mutat 2002 Dec;20:480. https://doi.org/10.1002/humu.9093.Search in Google Scholar
11. Santer, R, Kinner, M, Steuerwald, U, Kjaergaard, S, Skovby, F, Simonsen, H, et al. Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur J Hum Genet 2001;9:388–91. https://doi.org/10.1038/sj.ejhg.5200632.Search in Google Scholar
12. Dagli, AI, Zori, RT, McCune, H, Ivsic, T, Maisenbacher, MK, Weinstein, DA. Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet. J Inherit Metab Dis 2009;32(Suppl 1):S103–6. https://doi.org/10.1007/s10545-009-1088-x.Search in Google Scholar
13. Valayannopoulos, V, Bajolle, F, Arnoux, JB, Dubois, S, Sannier, N, Baussan, C, et al. Successful treatment of severe cardiomyopathy in glycogen storage disease type III With D,L-3-hydroxybutyrate, ketogenic and high-protein diet. Pediatr Res 2011;70:638–41. https://doi.org/10.1203/pdr.0b013e318232154f.Search in Google Scholar
14. El-Karaksy, H, El-Raziky, MS, Anwar, G, Mogahed, E. The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III. J Pediatr Endocrinol Metab 2015;28:195–200. https://doi.org/10.1515/jpem-2014-0145.Search in Google Scholar
15. Kondo, Y, Usui, H, Ishige-Wada, M, Murase, T, Owada, M, Okubo, M. Liver cirrhosis treated by living donor liver transplantation in a patient with AGL mutation c.2607-2610delATTC and c.1672dupA. Clin Chim Acta 2013;424:19–21. https://doi.org/10.1016/j.cca.2013.05.007.Search in Google Scholar
16. Matern, D, Starzl, TE, Arnaout, W, Barnard, J, Bynon, JS, Dhawan, A, et al. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr 1999;158(Suppl 2):S43–8. https://doi.org/10.1007/pl00014320.Search in Google Scholar
17. Liu, KM, Wu, JY, Chen, YT. Mouse model of glycogen storage disease type III. Mol Genet Metab 2014;111:467–76. https://doi.org/10.1016/j.ymgme.2014.02.005.Search in Google Scholar
18. Yi, H, Thurberg, BL, Curtis, S, Austin, S, Fyfe, J, Koeberl, DD, et al. Characterization of a canine model of glycogen storage disease type IIIa. Dis Model Mech 2012;5:804–11. https://doi.org/10.1242/dmm.009712.Search in Google Scholar
19. Yi, H, Brooks, ED, Thurberg, BL, Fyfe, JC, Kishnani, PS, Sun, B. Correction of glycogen storage disease type III with rapamycin in a canine model. J Mol Med (Berl) 2014;92:641–50. https://doi.org/10.1007/s00109-014-1127-4.Search in Google Scholar
20. Sun, B, Fredrickson, K, Austin, S, Tolun, AA, Thurberg, BL, Kraus, WE, et al. Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III. Mol Genet Metab 2013;108:145–7. https://doi.org/10.1016/j.ymgme.2012.12.002.Search in Google Scholar
21. Demo, E, Frush, D, Gottfried, M, Koepke, J, Boney, A, Bali, D, et al. Glycogen storage disease type III-hepatocellular carcinoma a long-term complication? J Hepatol 2007;46:492–8. https://doi.org/10.1016/j.jhep.2006.09.022.Search in Google Scholar
22. Lee, P, Burch, M, Leonard, JV. Plasma creatine kinase and cardiomyopathy in glycogen storage disease type III. J Inherit Metab Dis 1995;18:751–2. https://doi.org/10.1007/bf02436768.Search in Google Scholar
23. Labrune, P, Huguet, P, Odievre, M. Cardiomyopathy in glycogen-storage disease type III: clinical and echographic study of 18 patients. Pediatr Cardiol 1991Jul;12:161–3. https://doi.org/10.1007/bf02238523.Search in Google Scholar
24. Carvalho, JS, Matthews, EE, Leonard, JV, Deanfield, J. Cardiomyopathy of glycogen storage disease type III. Heart Vessels 1993;8:155–9. https://doi.org/10.1007/bf01744800.Search in Google Scholar
25. Hobson-Webb, LD, Austin, SL, Bali, DS, Kishnani, PS. The electrodiagnostic characteristics of glycogen storage disease type III. Genet Med. 2010;12:440–5. https://doi.org/10.1097/gim.0b013e3181cd735b.Search in Google Scholar
26. Decostre, V, Laforet, P, De Antonio, M, Kachetel, K, Canal, A, Ollivier, G, et al. Long term longitudinal study of muscle function in patients with glycogen storage disease type IIIa. Mol Genet Metab 2017;122:108–16. https://doi.org/10.1016/j.ymgme.2017.08.010.Search in Google Scholar
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/ijcre-2019-0226).
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Articles
- Definition and early diagnosis of metabolic syndrome in children
- Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment
- Original Articles
- Association of sleep characteristics with adiposity markers in children
- Prevalence of abdominal obesity in non-obese adolescents: a North Indian adolescent study
- Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes
- Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes
- Association between eating behavior, anthropometric and biochemical measurements, and peptide YY (PYY) hormone levels in obese adolescents in outpatient care
- Autoimmune hyperthyroidism in children & adolescents in Sudan: a 13 years’ experience of a Paediatric Endocrinology Clinic
- Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome
- Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt
- Quality of life and associated factors in parents of children with late diagnosed phenylketonuria. A cross sectional study in a developing country (Tunisia)
- Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa
- Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study
- Menstrual cycle, reproductive function, body mass index, and metabolic profiles of women with former central precocious puberty: 10–20-year longitudinal cohort study in southern Thailand
- Letter to the Editors
- European Society of Paediatric Radiology (ESPR) Child Abuse Taskforce Committee: a response to Miller et al.
- The correct formula to calculate triglyceride-glucose index (TyG)
- Case Reports
- Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism
- Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report
- Three patients with glucose-6 phosphatase catalytic subunit 3 deficiency
- Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism
Articles in the same Issue
- Frontmatter
- Review Articles
- Definition and early diagnosis of metabolic syndrome in children
- Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment
- Original Articles
- Association of sleep characteristics with adiposity markers in children
- Prevalence of abdominal obesity in non-obese adolescents: a North Indian adolescent study
- Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes
- Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes
- Association between eating behavior, anthropometric and biochemical measurements, and peptide YY (PYY) hormone levels in obese adolescents in outpatient care
- Autoimmune hyperthyroidism in children & adolescents in Sudan: a 13 years’ experience of a Paediatric Endocrinology Clinic
- Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome
- Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt
- Quality of life and associated factors in parents of children with late diagnosed phenylketonuria. A cross sectional study in a developing country (Tunisia)
- Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa
- Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study
- Menstrual cycle, reproductive function, body mass index, and metabolic profiles of women with former central precocious puberty: 10–20-year longitudinal cohort study in southern Thailand
- Letter to the Editors
- European Society of Paediatric Radiology (ESPR) Child Abuse Taskforce Committee: a response to Miller et al.
- The correct formula to calculate triglyceride-glucose index (TyG)
- Case Reports
- Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism
- Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report
- Three patients with glucose-6 phosphatase catalytic subunit 3 deficiency
- Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism
