Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review

Lu, Shi-Qi; Feng, Juan; Liu, Jie; Xie, Xin‐Bao; Lu, Yi; Abuduxikuer, Kuerbanjiang

doi:10.1515/jpem-2020-0173

Cited by 7 publications

(17 citation statements)

References 32 publications

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“…GSD VI is usually considered a relatively mild disorder [1]; however, more severe cases with recurrent hypoglycemia, liver cirrhosis or developmental delay have been reported [6][7][8]. Phenotypic information on GSD VI is currently only available from published case reports and small case series.…”

Section: Discussionmentioning

confidence: 99%

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The Phenotypic and Genetic Spectrum of Glycogen Storage Disease Type VI

Grünert

Hannibal

Spiekerkoetter

2021

Genes

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Glycogen storage disease type VI (GSD VI) is an autosomal recessive disorder of glycogen metabolism due to mutations in the glycogen phosphorylase gene (PYGL), resulting in a deficiency of hepatic glycogen phosphorylase. We performed a systematic literature review in order to collect information on the clinical phenotypes and genotypes of all published GSD VI patients and to compare the data to those for GSD IX, a biochemically and clinically very similar disorder caused by a deficiency of phosphorylase kinase. A total of 63 genetically confirmed cases of GSD VI with clinical information were identified (median age: 5.3 years). The age at presentation ranged from 5 weeks to 38 years, with a median of 1.8 years. The main presenting symptoms were hepatomegaly and poor growth, while the most common laboratory findings at initial presentation comprised elevated activity of liver transaminases, hypertriglyceridemia, fasting hypoglycemia and postprandial hyperlactatemia. Liver biopsies (n = 37) showed an increased glycogen content in 89.2%, liver fibrosis in 32.4% and early liver cirrhosis in 10.8% of cases, respectively. No patient received a liver transplant, and one successful pregnancy was reported. Our review demonstrates that GSD VI is a disorder with broad clinical heterogeneity and a small number of patients with a severe phenotype and liver cirrhosis. Neither clinical nor laboratory findings allow for a differentiation between GSD VI and GSD IX. Early biochemical markers of disease severity or clear genotype phenotype correlations are missing. Given the overall benign and unspecific phenotype and the need for enzymatic or genetic analyses for confirmation of the diagnosis, GSD VI is likely underdiagnosed. With new treatment approaches in sight, early, pre-symptomatic diagnosis, especially with respect to hepatic cirrhosis, will become even more important.

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Section: Discussionmentioning

confidence: 99%

“…Especially, long-term outcome data on patients with GSD VI are scarce. Published findings suggest significant clinical heterogeneity, and although GSD VI is usually considered a relatively mild disorder [1], some severe cases with recurrent hypoglycemia, liver cirrhosis or developmental delay have been described [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

The Phenotypic and Genetic Spectrum of Glycogen Storage Disease Type VI

Grünert

Hannibal

Spiekerkoetter

2021

Genes

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“…GSD type VI was previously considered as a mild disease. However, recent reports highlighted the possibility of a progression to fibrosis and cirrhosis, and a degeneration to hepatocellular carcinoma, so a rigorous long-term monitoring of hepatic function is needed [ 4 , 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…In GSD type IV the accumulation of abnormal glycogen, less soluble than normal glycogen, causes a foreign body reaction with consequent osmotic swelling and cell death [ 50 ], leading to interstitial fibrosis evolving toward cirrhosis [ 24 ]. Liver fibrosis is outlined also in individuals with GSD types VI [ 38 , 66 ] and IX [ 4 , 51 ]. Particularly, in GSD type IX fibrosis has been recently reported to range between 33 and 95% depending on the subtype still in early infancy [ 4 ].…”

Section: Resultsmentioning

confidence: 99%

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Glycogen storage diseases with liver involvement: a literature review of GSD type 0, IV, VI, IX and XI

Massese

Tagliaferri

Dionisi‐Vici

et al. 2022

Orphanet J Rare Dis

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Background Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs. Main body Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms, whose presentation can be similar. Compared to GSD type I and III, which are characterized by a more severe impact on metabolic and glycemic homeostasis, GSD type 0, VI, IX and XI are usually known to be responsive to the nutritional treatment for achieving a balanced metabolic homeostasis in the pediatric age. However, some patients can exhibit a more severe phenotype and an important progression of the liver and muscular disease. The effects of dietary adjustments in GSD type IV are encouraging, but data are limited. Conclusions Early diagnosis allows a good metabolic control, with improvement of quality of life and prognosis, therefore we underline the importance of building a proper knowledge among physicians about these rare conditions. Regular monitoring is necessary to restrain disease progression and complications.

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