Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia

Hannah, William B.; Ong, Ricardo C.; Moreno, Margarita Nieto; Pendyal, Surekha; Abdelmalak, Monica; Kelsen, Judith R.; McGreal, Nancy; Kishnani, Priya S.

doi:10.1016/j.ymgmr.2022.100848

Cited by 2 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These complications are attributed to hypothalamic-pituitary-adrenal (HPA) axis stimulation due to chronic hypoglycemic stress causing elevated glucocorticoid secretion [25]. In our study cohort, inflammatory bowel disease (IBD) was present in 15 patients (37.5%) (see S1 Table ), that is higher as studies have reported an occasional presence of IBD in GSD Ia cases [26,27]. Disease causing variant analysis of GSD Ia in 20 selected cases identified four novel missense variants i.e., c.109G>C(p.Ala37Pro), c.205G>A(p.Asp69Asn), c.244C>A (p.Gln82Lys) and c.322A>C(p.Thr108Pro) and an insertion c.49_50insT in homozygous condition.…”

Section: Plos Onementioning

confidence: 73%

Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan

Gul,

Firasat,

Shan

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Glycogen storage disease type I (GSD I) is a rare autosomal recessive inborn error of carbohydrate metabolism caused by the defects of glucose-6-phosphatase complex (G6PC). Disease causing variants in the G6PC gene, located on chromosome 17q21 result in glycogen storage disease type Ia (GSD Ia). Age of onset of GSD Ia ranges from 0.5 to 25 years with presenting features including hemorrhage, hepatic, physical and blood related abnormalities. The overall goal of proposed study was clinical and genetic characterization of GSD Ia cases from Pakistani population. This study included forty GSD Ia cases presenting with heterogeneous clinical profile including hypoglycemia, hepatomegaly, lactic acidosis i.e., pH less than 7.2, hyperuricemia, seizures, epistaxis, hypertriglyceridemia (more than180 mg/dl) and sometimes short stature. All coding exons and intron-exon boundaries of G6PC gene were screened to identify pathogenic variant in 20 patients based on availability of DNA samples and willingness to participate in molecular analysis. Pathogenic variant analysis was done using PCR-Sanger sequencing method and pathogenic effect predictions for identified variants were carried out using PROVEAN, MutationTaster, Polyphen 2, HOPE, Varsome, CADD, DANN, SIFT and HSF software. Overall, 21 variants were detected including 8 novel disease causing variants i.e., G6PC (NM_000151.4):c.71A>C (p.Gln24Pro), c.109G>C(p.Ala37Pro), c.133G>C(p.Val45Leu), c.49_50insT c.205G>A(p.Asp69Asn), c.244C>A(p.Gln82Lys) c.322A>C(p.Thr108Pro) and c.322A>C(p.Cys284Tyr) in the screened regions of G6PC gene. Out of 13 identified polymorphisms, 3 were identified in heterozygous condition while 10 were found in homozygous condition. This study revealed clinical presentation of GSD Ia cases from Pakistan and identification of novel disease-causing sequence variants in coding region and intron-exon boundaries of G6PC gene.

show abstract

Section: Plos Onementioning

confidence: 73%

Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan

Gul,

Firasat,

Shan

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The authors speculated that inflammatory bowel disease in GSD-Ia may be caused by chronic UCCS therapy, which could be altering the microbiota of the gastrointestinal tract leading to inflammation. More recently, very early onset inflammatory bowel disease was reported in a child with GSD-Ia at the age of 42 mo[ 46 ].…”

Section: Gsds Involving Livermentioning

confidence: 99%

Glycogen storage diseases: An update

Gümüş¹,

Özen²

2023

World J Gastroenterol

View full text Add to dashboard Cite

Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.

show abstract

Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia

Cited by 2 publications

References 13 publications

Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan

Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan

Glycogen storage diseases: An update

Contact Info

Product

Resources

About