A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data.
Clinicopathologic
G6PC gene
GSD-Ia
Hepatic adenomas
Liver transplant-treated
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
06 May 2024
06 May 2024
Historique:
received:
07
12
2023
accepted:
22
04
2024
medline:
7
5
2024
pubmed:
7
5
2024
entrez:
6
5
2024
Statut:
epublish
Résumé
Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
Sections du résumé
BACKGROUND
BACKGROUND
Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay.
CASE PRESENTATION
METHODS
Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.
CONCLUSION
CONCLUSIONS
The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
Identifiants
pubmed: 38711024
doi: 10.1186/s12920-024-01888-6
pii: 10.1186/s12920-024-01888-6
doi:
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
124Subventions
Organisme : Panzhihua City Medical Research Center Project
ID : PYYZ-2022-03
Organisme : Panzhihua City Medical Research Center Project
ID : PYYZ-2022-03
Organisme : Panzhihua City Medical Research Center Project
ID : PYYZ-2022-03
Organisme : Panzhihua City Medical Research Center Project
ID : PYYZ-2022-03
Organisme : Panzhihua City Medical Research Center Project
ID : PYYZ-2022-03
Organisme : Sichuan Province Science and Technology Support Program
ID : 2021YJ0168
Organisme : Sichuan Province Science and Technology Support Program
ID : 2021YJ0168
Organisme : Sichuan Province Science and Technology Support Program
ID : 2021YJ0168
Organisme : Sichuan Province Science and Technology Support Program
ID : 2021YJ0168
Organisme : Sichuan Province Science and Technology Support Program
ID : 2021YJ0168
Informations de copyright
© 2024. The Author(s).
Références
Kido J, Nakamura K, Matsumoto S, et al. Current status of hepatic glycogen storage disease in Japan: clinical manifestations, treatments and long-term outcomes[J]. J Hum Genet. 2013;58(5):285–92.
doi: 10.1038/jhg.2013.17
pubmed: 23486339
Sun B, Brooks ED, Koeberl DD. Preclinical development of new therapy for glycogen storage diseases[J]. Curr Gene Ther. 2015;15(4):338–47.
doi: 10.2174/1566523215666150630132253
pubmed: 26122079
pmcid: 4682885
Hicks J, Wartchow E, Mierau G. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment[J]. Ultrastruct Pathol. 2011;35(5):183–96.
doi: 10.3109/01913123.2011.601404
pubmed: 21910565
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
pubmed: 25356975
Chou JY, Matern D, Mansfield BC, Chen YT. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. Curr Mol Med [J]. 2002;2(2):121–43.
doi: 10.2174/1566524024605798
pubmed: 11949931
Chou JY, Jun HS, Mansfield BC. Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy[J]. Nat Rev Endocrinol. 2010;6(12):676–88.
doi: 10.1038/nrendo.2010.189
pubmed: 20975743
pmcid: 4178929
Chou JY, Jun HS, Mansfield BC. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase/glucose-6-phosphate transporter complexes[J]. J Inherit Metab Dis. 2015;38(3):511–9.
doi: 10.1007/s10545-014-9772-x
pubmed: 25288127
Chen YT. Glycogen storage diseases[M]//Behrman RE. The Nelson textbook of pediatrics. 17th ed. Philadephia, Pennsylvania: Saunders Company; 2004. p. 469–75.
Kanamori H, Nakade Y, Yamamoto T, et al. Case of cholangiocellular carcinoma in a patient with glycogen storage disease type Ia[J]. Hepatol Res. 2015;45(4):494–9.
doi: 10.1111/hepr.12366
pubmed: 24905794
Li X, Jing H, Cheng L, et al. A case study of glycogen storage disease type Ia presenting with multiple hepatocellular adenomas: an analysis by gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid magnetic resonance imaging[J]. Quant Imaging Med Surg. 2021;11(6):2785–91.
doi: 10.21037/qims-20-746
pubmed: 34079743
pmcid: 8107322
Singh Y, Gurung S, Gogtay M. Glycogen hepatopathy in type-1 diabetes mellitus: A case report[J]. World J Hepatol. 2022;14(2):471–8.
doi: 10.4254/wjh.v14.i2.471
pubmed: 35317186
pmcid: 8891674
Chou JY, Kim GY, Cho JH. Recent development and gene therapy for glycogen storage disease type Ia. Liver Res. 2017;1(3):174–80.
doi: 10.1016/j.livres.2017.12.001
pubmed: 29576889
pmcid: 5859325
Szymańska E, Jóźwiak-Dzięcielewska DA, Gronek J, et al. Hepatic glycogen storage diseases: pathogenesis, clinical symptoms and therapeutic management[J]. Arch Med Sci. 2019;17(2):304–13.
doi: 10.5114/aoms.2019.83063
pubmed: 33747265
pmcid: 7959092
Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6-phosphatase deficiency [J]. Orphanet J Rare Dis. 2011;6:27.
doi: 10.1186/1750-1172-6-27
pubmed: 21599942
pmcid: 3118311
Lei KJ, Chen H, Pan CJ, et al. Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type-1a mouse [J]. Nat Genet. 1996;13(2):203–9.
doi: 10.1038/ng0696-203
pubmed: 8640227
Moses SW. Historical highlights and unsolved problems in glycogen storage disease type 1[J]. Eur J Pediatr. 2002;161(Suppl 1):S2–9.
doi: 10.1007/BF02679988
pubmed: 12373565
Talente GM, Coleman RA, Alter C, et al. Glycogen storage disease in adults [J]. Ann Intern Med. 1994;120(3):218–26.
doi: 10.7326/0003-4819-120-3-199402010-00008
pubmed: 8273986
Zhu J, Xing Y, Xing X, et al. A novel type heterozygous mutation in the glucose-6-phosphatase gene in a Chinese patient with glycogen storage disease Ia [J]. Gene. 2012;511(1):122–4.
doi: 10.1016/j.gene.2012.09.020
pubmed: 23000067
Zheng BX, Lin Q, Li M, et al. Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia [J]. Eur J Pediatr. 2015;174(1):59–63.
doi: 10.1007/s00431-014-2354-y
pubmed: 24980439
Germann R, Schindera F. [Von Gierke’s glycogenosis. First description in a female patient in the Karlsruhe Franz Lust pediatric clinic in 1929]. Dtsch Med Wochenschr. 1996;121(17):572–3.
doi: 10.1055/s-0029-1234181
pubmed: 8620828
Cori GT, Cori CF. Glucose-6-phosphatase of the liver in glycogen storage disease [J]. J Biol Chem. 1952;199(2):661–7.
doi: 10.1016/S0021-9258(18)38504-1
pubmed: 13022673
Friedman LS, Ostermeyer EA, Lynch ED, et al. 22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors [J]. Genomics. 1995;25(1):256–63.
doi: 10.1016/0888-7543(95)80133-7
pubmed: 7774926
Chou JY, Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease [J]. Hum Mutat. 2008;29(7):921–30.
doi: 10.1002/humu.20772
pubmed: 18449899
pmcid: 2475600
Sperb-Ludwig F, Pinheiro FC, Bettio Soares M, et al. Glycogen storage diseases: Twenty-seven new variants in a cohort of 125 patients. Mol Genet Genomic Med [J]. 2019;7(11):e877.
doi: 10.1002/mgg3.877
pubmed: 31508908
Qiu WJ, Gu XF, Ye J, et al. Gene mutation and clinical study in the patients with glycogen storage disease type Ia [J]. Chin J Endocrinol Metab. 2004;20(6):502–5.
Akanuma J, Nishigaki T, Fujii K, et al. Glycogen storage disease type Ia: molecular diagnosis of 51 Japanese patients and characterization of splicing mutations by analysis of ectopically transcribed mRNA from lymphoblastoid cells [J]. Am J Med Genet. 2000;91(2):107–12.
doi: 10.1002/(SICI)1096-8628(20000313)91:2<107::AID-AJMG5>3.0.CO;2-Y
pubmed: 10748407
Liang CL, Liu L, Sheng HY, et al. Analysis of gene mutations and clinical manifestations in 20 patients with glycogen storage disease type Ia [J]. Chin J Appl Pediatr. 2013;28(8):581–5.
Jang HJ, Yang HR, Ko JS, et al. Development of Hepatocellular Carcinoma in Patients with Glycogen Storage Disease: a Single Center Retrospective Study [J]. J Korean Med Sci. 2020;35(1):e5.
doi: 10.3346/jkms.2020.35.e5
pubmed: 31898434
Miles L, Heubi JE, Bove KE. Hepatocyte glycogen accumulation in patients undergoing dietary management of urea cycle defects mimics storage disease [J]. J Pediatr Gastroenterol Nutr. 2005;40(4):471–6.
doi: 10.1097/01.MPG.0000157200.33486.CE
pubmed: 15795597
Mertens J, De Block C, Spinhoven M, et al. Hepatopathy associated with type 1 diabetes: distinguishing non-alcoholic fatty liver disease from glycogenic hepatopathy [J]. Front Pharmacol. 2021;12: 768576.
doi: 10.3389/fphar.2021.768576
pubmed: 34759828
pmcid: 8573337
Torbenson M. Hepatic Adenomas: Classification, controversies, and consensus. Surg Pathol Clin. 2018;11(2):351–66.
doi: 10.1016/j.path.2018.02.007
pubmed: 29751879
Bhattacharya K. Investigation and management of the hepatic glycogen storage diseases [J]. Transl Pediatr. 2015;4(3):240–8.
pubmed: 26835382
pmcid: 4729058
Beyzaei Z, Shamsaeefar A, Kazemi K, et al. Liver transplantation in glycogen storage disease: a single-center experience [J]. Orphanet J Rare Dis. 2022;17(1):127.
doi: 10.1186/s13023-022-02284-y
pubmed: 35313948
pmcid: 8935097
Yavarow ZA, Kang HR, Waskowicz LR, et al. Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia [J]. Hum Mol Genet. 2020;29(2):286–94.
doi: 10.1093/hmg/ddz290
pubmed: 31816064
Li X, Jing H, Cheng L, et al. A case study of glycogen storage disease type Ia presenting with multiple hepatocellular adenomas: an analysis by gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid magnetic resonance imaging [J]. Quant Imaging Med Surg. 2021;11(6):2785–91.
doi: 10.21037/qims-20-746
pubmed: 34079743
pmcid: 8107322