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Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

ABSTRACT: Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-α) and glucose-6-phosphate-transporter (G6PT), respectively. For the past 50 years, the care of patients with GSDI has been improved following elaborate dietary managements. GSDI patients currently receive dietary therapies that enable patients to improve hypoglycemia and alleviate early symptomatic signs of the disease. However, dietary therapies have many limitations with a risk of calcium, vitamin D, and iron deficiency and cannot prevent long-term complications, such as progressive liver and renal failure. With the deepening understanding of the pathogenesis of GSDI and the development of gene therapy technology, there is great progress in the treatment of GSDI. Here, we review the underlying molecular genetics and the current clinical management strategies of GSDI patients with an emphasis on promising experimental gene therapies.

SUBMITTER: Zhong J

PROVIDER: S-EPMC10874634 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

Zhong Jiamin J Gou Yannian Y Zhao Piao P Dong Xiangyu X Guo Meichun M Li Aohua A Hao Ailing A Luu Hue H HH He Tong-Chuan TC Reid Russell R RR Fan Jiaming J

Pediatric discovery 20230724 2

Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-α) and glucose-6-phosphate-tra ...[more]

PMID: 38370424

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Project description:ImportanceGlycogen storage disease type Ib (GSDIb) is a rare metabolic disorder characterized by impaired glucose-6-phosphate transporter function with limited descriptions.ObjectiveTo describe the genetic and clinical features of Chinese patients with GSDIb.Design, setting, and participantsThis retrospective cohort study retrieved the medical records of 113 Chinese patients with GSDIb treated at a single institution in Shanghai from November 1, 2000, to June 30, 2024.Main outcomes and measuresBiochemical parameters and clinical features (infections, inflammatory bowel disease [IBD], kidney and cardiovascular issues, growth and puberty) at baseline and the last follow-up, all-cause mortality, and mental and social development were assessed.ResultsA total of 113 patients (96 children [85%]; 67 males [59%]) had GSDIb genetically diagnosed at a median age of 1.4 (range, 0.0-35.5) years. Thirty-eight novel SLC37A4 variants were identified. Hypoglycemia and metabolic derangements were the primary concerns in patients aged 2 years or younger (45%). Short stature (75%), infections (75%), and recurrent epistaxis (31%) became more prevalent in patients aged 2.1 to 5.0 years. The frequency of respiratory tract infection decreased after a median age of 7.0 (IQR, 3.5-10.5) years. Forty-four patients (46%) developed IBD at a median age of 6.0 (IQR, 3.0-12.0) years, 14% of whom developed IBD-associated arthritis at a median age of 10.5 (IQR, 5.8-19.6) years. The mean (SD) difference between the z scores of actual height and target height (Δ height z scores) at the final visit (-2.11 [1.76]) did not significantly increase even after uncooked cornstarch treatment. The mean (SD) Δ height z scores of the patients with IBD (-2.99 [1.70]) were significantly lower than those without IBD (mean [SD], -1.36 [1.44]) (P < .001). Ten patients (9%) died due to complications of GSDIb, including metabolic derangements, sepsis, and/or severe pneumonia (n = 8), IBD (n = 1), and pulmonary hypertension (n = 1).Conclusions and relevanceIn this cohort study, the genetic and clinical spectra of GSDIb were broadened, suggesting associations between GSDIb and bowel, growth, and survival outcomes. To date, no previous study reported IBD-associated arthritis.

Project description:Coronavirus disease 2019 (COVID-19), which reported in an outbreak in 2019 in Wuhan, Hubei province, China, is caused by the SARS-CoV-2 virus. The virus belongs to the beta-coronavirus class, along with the Middle East Respiratory Syndrome coronavirus and Severe Acute Respiratory Syndrome coronavirus. Interestingly, the virus binds with angiotensin-converting enzyme-2 found in host cells, through the spike (S) protein that exists on its surface. This binding causes the entry of the virus into cells of the host organism. The actual mechanism used by the COVID-19 virus to induce disease is still speculative. A total of 44,322,504 cases, a 1,173,189 death toll and 32,486,703 recovery cases have been reported in 217 countries globally as of 28 October 2020. Symptoms from the infection of the virus include chest pain, fever, fatigue, nausea, and others. Acute respiratory stress syndrome, arrhythmia, and shock are some of the chronic manifestations recorded in severe COVID-19. Transmission is majorly by individual-to-individual through coughing, sneezing, etc. The lack of knowledge regarding the mechanism of and immune response to the virus has posed a challenge in the development of a novel drug and vaccine. Currently, treatment of the disease involves the use of anti-viral medications such as lopinavir, remdesivir, and other drugs. These drugs show some efficacy in the management of COVID-19. Studies are still on-going for the development of an ideal and novel drug for treatment. In terms of natural product intervention, Traditional Chinese Medicines (TCM) have been employed to alleviate the clinical manifestation and severity of the disease and have shown some efficacy. This review presents an updated detailed overview of COVID-19 and the virus, concerning its structure, epidemiology, symptoms and transmission, immune responses, and current interventions, and highlights the potential of TCM. It is anticipated that this review will further add to the understanding of COVID-19 and the virus, hence opening new research perspectives.

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Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

Publications

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

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