Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases

Yuchuan LI; Yi LU; Jiayan FENG; Jianshe WANG

doi:10.3969/j.issn.1001-5256.2021.02.026

Volume 37 Issue 2

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(2): 380-384

PDF( 2251 KB)

Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases

DOI: 10.3969/j.issn.1001-5256.2021.02.026

a.
Department of Hepatology, Children's Hospital of Fudan University, Shanghai 201102, China
b.
Department of Pathology, Children's Hospital of Fudan University, Shanghai 201102, China

Received Date: 2020-08-01
Accepted Date: 2020-10-28
Published Date: 2021-02-20

Abstract

Abstract

Objective To investigate the clinical and genetic features of patients with glycogen storage disease type Ⅸa (GSD Ⅸa), and to improve the clinical understanding of the disease. Methods A retrospective analysis was performed for the clinical data of 20 patients who were hospitalized and genetically diagnosed with GSD Ⅸa in Children's Hospital of Fudan University from January 2015 to December 2018, and their clinical and genetic features were summarized. Results All 20 patients with GSD Ⅸa were male, with a median age of 2.5 years at the time of confirmed diagnosis. All patients had hepatomegaly and elevated aminotransferases; of all patients, there were 5 patients (25.0%) with growth retardation, 19 (95.0%) with fasting hypoglycemia, 14 (70.0%) with hyperlactatemia, 9 (45.0%) with hypertriglyceridemia, and 5 (25.0%) with hypercholesterolemia. Fasting blood ketone was measured for 8 patients and all of these patients had an increase in blood ketone; all patients had normal uric acid, and 5 patients (25.0%) had positive urine ketone. Liver biopsy was performed for 18 patients, among whom 15 had mild to moderate liver fibrosis. A total of 16 mutations were detected in the PHKA2 gene, among which 5 were known pathogenic mutations and 11 were novel mutations, and most of the mutations were detected in the c.3614 locus. All patients were treated with uncooked cornstarch, and most patients achieved an improvement in clinical manifestations. Conclusion GSD Ⅸa is more common in male patients. This disease should be considered for patients with hepatomegaly, elevated aminotransferases, growth retardation, fasting hypoglycemia, elevated fasting blood ketone, and normal uric acid. Liver biopsy may help with the diagnosis of this disease, and clinical biochemical parameters and gene detection can be used to confirm diagnosis and classification. Most patients have mild clinical manifestations, while some patients may have liver fibrosis, and treatment with uncooked cornstarch can improve the condition of this disease.
- Glycogen Storage Disease,
- Pathological Conditions, Signs and Symptoms,
- Mutation

FullText(HTML)

References(27)

References

[1]	ACHOUITAR S, GOLDSTEIN JL, MOHAMED M, et al. Common mutation in the PHKA2 gene with variable phenotype Ⅰn patients with liver phosphorylase b kinase deficiency[J]. Mol Genet Metab, 2011, 104(4): 691-694. DOI: 10.1016/j.ymgme.2011.08.021
[2]	MAICHELE AJ, BURWINKEL B, MAIRE I, et al. Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans[J]. Nat Genet, 1996, 14(3): 337-340. DOI: 10.1038/ng1196-337
[3]	BRUSHIA RJ, WALSH DA. Phosphorylase kinase: The complexity of its regulation is reflected in the complexity of its structure[J]. Front Biosci, 1999, 4: d618-d641.
[4]	DAVIDSON JJ, OZÇELIK T, HAMACHER C, et al. cDNA cloning of a liver isoform of the phosphorylase kinase alpha subunit and mapping of the gene to Xp22.2-p22.1, the region of human X-linked liver glycogenosis[J]. Proc Natl Acad Sci U S A, 1992, 89(6): 2096-2100. DOI: 10.1073/pnas.89.6.2096
[5]	FU J, WANG T, XIAO X. A novel PHKA2 mutation in a Chinese child with glycogen storage disease type Ⅸa: A case report and literature review[J]. BMC Med Genet, 2019, 20(1): 56. DOI: 10.1186/s12881-019-0789-8
[6]	LIU J, ZHANG MH, GONG JY, et al. Report of 7 cases of glycogen storage disease type Ⅵ and type Ⅸa[J]. Chin J Evid Based Pediatr, 2017, 12(4): 284-288. (in Chinese) DOI: 10.3969/j.issn.1673-5501.2017.04.009 刘杰, 张梅红, 龚敬宇, 等.糖原累积病Ⅵ型和Ⅹa型7例病例报告并文献复习[J].中国循证儿科杂志, 2017, 12(4): 284-288. DOI: 10.3969/j.issn.1673-5501.2017.04.009
[7]	KISHNANI PS, GOLDSTEIN J, AUSTIN SL, et al. Diagnosis and management of glycogen storage diseases type Ⅵ and Ⅸ: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2019, 21(4): 772-789. DOI: 10.1038/s41436-018-0364-2
[8]	FERNANDES J, PIKAAR NA. Ketosis in hepatic glycogenosis[J]. Arch Dis Child, 1972, 47(251): 41-46. DOI: 10.1136/adc.47.251.41
[9]	ZHANG J, YUAN Y, MA M, et al. Clinical and genetic characteristics of 17 Chinese patients with glycogen storage disease type Ⅸa[J]. Gene, 2017, 627: 149-156. DOI: 10.1016/j.gene.2017.06.026
[10]	BEAUCHAMP NJ, DALTON A, RAMASWAMI U, et al. Glycogen storage disease type Ⅸ: High variability in clinical phenotype[J]. Mol Genet Metab, 2007, 92(1-2): 88-99. DOI: 10.1016/j.ymgme.2007.06.007
[11]	HIRONO H, SHOJI Y, TAKAHASHI T, et al. Mutational analyses in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1[J]. J Inherit Metab Dis, 1998, 21(8): 846-852. DOI: 10.1023/A:1005422819207
[12]	ROSCHER A, PATEL J, HEWSON S, et al. The natural history of glycogen storage disease types Ⅵ and Ⅸ: Long-term outcome from the largest metabolic center in Canada[J]. Mol Genet Metab, 2014, 113(3): 171-176. DOI: 10.1016/j.ymgme.2014.09.005
[13]	BURWINKEL B, AMAT L, GRAY RG, et al. Variability of biochemical and clinical phenotype Ⅰn X-linked liver glycogenosis with mutations in the phosphorylase kinase PHKA2 gene[J]. Hum Genet, 1998, 102(4): 423-429. DOI: 10.1007/s004390050715
[14]	KISHNANI PS, AUSTIN SL, ABDENUR JE, et al. Diagnosis and management of glycogen storage disease type Ⅰ: A practice guideline of the American College of Medical Genetics and Genomics[J]. Genet Med, 2014, 16(11): e1. DOI: 10.1038/gim.2014.128
[15]	HONG FX, QIU HR, XUE ZJ, et al. Management of fluid and metabolic/electrolytic disorders in living donor with liver transplantation in children with glycogen storage disease[J]. J Clin Exp Med, 2020, 19(1): 91-95. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-SYLC202001026.htm 洪方晓, 仇焕容, 薛照静, 等.糖原贮积病患儿行肝移植手术术中液体及内环境的管理[J].临床和实验医学杂志, 2020, 19(1): 91-95. https://www.cnki.com.cn/Article/CJFDTOTAL-SYLC202001026.htm
[16]	TSILIANIDIS LA, FISKE LM, SIEGEL S, et al. Aggressive therapy improves cirrhosis in glycogen storage disease type Ⅸ[J]. Mol Genet Metab, 2013, 109(2): 179-182. DOI: 10.1016/j.ymgme.2013.03.009
[17]	JOHNSON AO, GOLDSTEIN JL, BALI D. Glycogen storage disease type Ⅸ: Novel PHKA2 missense mutation and cirrhosis[J]. J Pediatr Gastroenterol Nutr, 2012, 55(1): 90-92. DOI: 10.1097/MPG.0b013e31823276ea
[18]	LAU CK, HUI J, FONG FN, et al. Novel mutations in PHKA2 gene in glycogen storage disease type Ⅸ patients from Hong Kong, China[J]. Mol Genet Metab, 2011, 102(2): 222-225. DOI: 10.1016/j.ymgme.2010.11.004
[19]	CHEN ST, CHEN HL, NI YH, et al. X-linked liver glycogenosis in a Taiwanese family: Transmission from undiagnosed males[J]. Pediatr Neonatol, 2009, 50(5): 230-233. DOI: 10.1016/S1875-9572(09)60068-1
[20]	WANG P, DONG Y, XU ZQ, et al. Clinical and pathological features and gene mutation analysis in 12 Chinese patients with glycogen storage disease type Ⅸ[J]. Chin Hepatol, 2018, 23(9): 764-768. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN201809007.htm 王璞, 董漪, 徐志强, 等.糖原累积症Ⅸ型12例临床、病理特点及基因突变位点分析[J].肝脏, 2018, 23(9): 764-768. https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN201809007.htm
[21]	YANG F, XU Y, FANG C, et al. Clinical and genetic characteristics of three Chinese patients with glycogen storage disease type Ⅸα[J]. Pediatr Neonatol, 2019, 60(4): 463-466. DOI: 10.1016/j.pedneo.2019.05.007
[22]	CHOI R, PARK HD, KANG B, et al. PHKA2 mutation spectrum in Korean patients with glycogen storage disease type Ⅸ: Prevalence of deletion mutations[J]. BMC Med Genet, 2016, 17: 33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839068/
[23]	CHO SY, LAM CW, TONG SF, et al. X-linked glycogen storage disease IXa manifested in a female carrier due to skewed X chromosome inactivation[J]. Clin Chim Acta, 2013, 426: 75-78. DOI: 10.1016/j.cca.2013.08.026
[24]	van den BERG IE, van BEURDEN EA, MALINGRÉ HE, et al. X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase alpha subunit[J]. Am J Hum Genet, 1995, 56(2): 381-387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801119/
[25]	HENDRICKX J, LEE P, KEATING JP, et al. Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type Ⅰ and Ⅱ[J]. Am J Hum Genet, 1999, 64(6): 1541-1549. DOI: 10.1086/302399
[26]	BURWINKEL B, MOSES SW, KILIMANN MW. Phosphorylase-kinase-deficient liver glycogenosis with an unusual biochemical phenotype Ⅰn blood cells associated with a missense mutation in the beta subunit gene (PHKB)[J]. Hum Genet, 1997, 101(2): 170-174. DOI: 10.1007/s004390050608
[27]	WILLEMS PJ, GERVER WJ, BERGER R, et al. The natural history of liver glycogenosis due to phosphorylase kinase deficiency: A longitudinal study of 41 patients[J]. Eur J Pediatr, 1990, 149(4): 268-271. DOI: 10.1007/BF02106291

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1) / Tables(2)

Get Citation

PDF

XML

Article Metrics

Article views (543) PDF downloads(54)

Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases

DOI: 10.3969/j.issn.1001-5256.2021.02.026

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases

DOI: 10.3969/j.issn.1001-5256.2021.02.026

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content