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There are no studies of hepatic glycogen storage diseases (GSDs) other than type I and III in Korea. We aimed on investigating the characteristics of hepatic GSDs in Korea diagnosed and followed at a single center.
We retrospectively analyzed patients who were diagnosed as GSD and followed at Samsung Medical Center from January, 1997 to December, 2...
Context in source publication
Citations
... Studies conducted previously focused mainly on strategies for preventing life-threatening hypoglycaemia, thus neglecting the short-and long-term metabolic complications of the disease [18,[32][33][34][35][36], which affect the quality of life and survival rates among patients with GSD [1,34,37,38]. The efficacy of the dietary treatment can be assessed in several ways. ...
... For patients with DM who present with hepatomegaly and elevated transaminase levels, there are several differential diagnoses apart from glycogenic hepatopathy, including NAFLD. Among T2DM patients, hepatic enlargement with elevated transaminases is usually the result of NAFLD, while GH is the most likely pathology in patients with T1DM [25] . Other potential causes of liver damage in people with diabetes include celiac disease and autoimmune hepatitis. ...
Glycogenic hepatopathy (GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease (NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.
... Since the GSD enzyme activity tests were first introduced in Korea, there have only been a few case reports of SLC37A4 mutations in Korean patients with GSD Ib [9][10][11][12]. Therefore, the aim of this study was to evaluate the mutation spectrum in Korean patients with GSD Ib for the first time, and to further compare the spectrum to previously reported mutation spectra reported for other ethnic populations. ...
Background
Molecular techniques are fundamental for establishing an accurate diagnosis and therapeutic approach of glycogen storage diseases (GSDs). We aimed to evaluate SLC37A4 mutation spectrum in Korean GSD Ib patients.
Methods
Nine Korean patients from eight unrelated families with GSD Ib were included. SLC37A4 mutations were detected in all patients with direct sequencing using a PCR method and/or whole-exome sequencing. A comprehensive review of previously reported SLC37A4 mutations was also conducted.
Results
Nine different pathogenic SLC37A4 mutations were identified in the nine patients with GSD Ib. Among them, four novel mutations were identified: c.148G>A (pGly50Arg), c.320G>A (p.Trp107*), c.412T>C (p.Trp138Arg), and c.818G>A (p.Gly273Asp). The most common mutation type was missense mutations (66.7%, 6/9), followed by nonsense mutations (22.2%, 2/9) and small deletion mutations (11.1%, 1/9). The most common mutation identified in the Korean population was c.443C>T (p.Ala148Val), which comprised 39.9% (7/18) of all tested alleles. This mutation has not been reported in GSD Ib patients in other ethnic populations.
Conclusions
This study expands knowledge of the SLC37A4 mutation spectrum in Korean patients with GSD Ib.
... From May 2010 to April 2015, blood samples from 13 unrelated Korean children were collected for PHKA2 mutation analysis at Samsung Medical Center. The study population included two female patients with hepatomegaly and elevated aspartate transaminase (AST) and/ or alanine transaminase (ALT) who were undergoing PHKA2 sequencing because no pathogenic mutations in G6PC (for GSD Ia), which is known to a common causative gene of glycogen storage disease in the Korean population, were identified during diagnostic work up for their hepatomegaly [10,11]. Blood samples from healthy individuals, who visited the health promotion center at Samsung Medical Center for regular health checkups without any clinical symptoms or signs of illnesses, and who volunteered for blood sampling, were also collected as negative controls for identified mutations. ...
Background
Molecular diagnosis of glycogen storage diseases (GSDs) is important to enable accurate diagnoses and make appropriate therapeutic plans. The aim of this study was to evaluate the PHKA2 mutation spectrum in Korean patients with GSD type IX.
Methods
Thirteen Korean patients were tested for PHKA2 mutations using direct sequencing and a multiplex polymerase chain reaction method. A comprehensive review of the literature on previously reported PHKA2 mutations in other ethnic populations was conducted for comparison.
Results
Among 13 patients tested, six unrelated male patients with GSD IX aged 2 to 6 years at the first diagnostic work-up for hepatomegaly with elevated aspartate transaminase (AST) and alanine transaminase (ALT) were found to have PHKA2 mutations. These patients had different PHKA2 mutations: five were known mutations (c.537 + 5G > A, c.884G > A [p.Arg295His], c.3210_3212delGAG [p.Arg1072del], exon 8 deletion, and exons 27–33 deletion) and one was a novel mutation (exons 18–33 deletion). Notably, the most common type of mutation was gross deletion, in contrast to other ethnic populations in which the most common mutation type was sequence variant.
Conclusions
This study expands our knowledge of the PHKA2 mutation spectrum of GSD IX. Considering the PHKA2 mutation spectrum in Korean patients with GSD IX, molecular diagnostic methods for deletions should be conducted in conjunction with direct sequence analysis to enable accurate molecular diagnosis of this disease in the Korean population.
Citation: Subih, H.S.; Qudah, R.A.; Janakat, S.; Rimawi, H.; Elsahoryi, N.A.; Alyahya, L. Medium-Chain
Citation: Subih, H.S.; Qudah, R.A.; Janakat, S.; Rimawi, H.; Elsahoryi, N.A.; Alyahya, L. Medium-Chain
Glycogen storage disease type IX (GSD IX) is caused by a deficiency of hepatic phosphorylase kinase. The aim of this study was to clarify the clinical features, long term outcomes, and genetic analysis of GSD IX in Korea. A GSD gene panel was created and hybridization capture-based next-generation sequencing was performed. We investigated clinical laboratory data, results of molecular genetic analysis, liver biopsy findings, and long-term outcomes. Ten children were diagnosed with GSD IX at Seoul National University Children's Hospital. Hypoglycemia, hyperlactacidemia, hypertriglyceridemia, hyperuricemia, liver fibrosis on liver biopsy, and short stature was found in 30%, 56%, 100%, 60%, 80% and 50% of the children, respectively. Seven PHKA2 variants were identified in eight children with GSD IXa—one nonsense (c.2268dupT; p.(Asp757Ter)), two splicing (c.918+1G > A, c.718-2 A > G), one frameshift (c.405_419delinsTCCTGGCC; p.(Asp136ProfsTer11)), and three missense variants (c.3628G > A; p.(Gly1210Arg), c.1245G > T and c.2746C > T; p.(Arg916Trp)). Two variants of PHKG2 were identified in two children with GSD IXc—one frameshift (c.783delC; p.(Ser262AlafsTer6)) and one missense (c.661G > A; p.(Val221Met)). Elevated liver enzymes and hypertriglyceridemia in children with GSD IXa tended to improve with age. For the first time, we report hepatocellular carcinoma in a patient with GSD IXc. The GSD gene panel is a useful diagnostic tool to confirm GSD IX. The clinical phenotype of GSD IXc is severe and monitoring for the development of hepatocellular carcinoma should be implemented.
