Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature

Abstract

No correlation was found between individual mutations and the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil differentiation, maturation and apoptosis and thus the severity and frequency of infections. The absence of detectable mutations in three patients could suggest that a second protein plays a role in microsomal phosphate transport.

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…Adult patients also have severe neutropenia and recurrent infections. 148 Patients are prone to development of gingivitis, mouth ulcers, upper respiratory infections, deep abscesses, and enterocolitis. The patterns of infections vary from patient to patient, but there is no clear genotypephenotype relationship.…”

Phagocyte dysfunction and inflammatory bowel disease

“…The clinical and metabolic features of hepatosplenomegaly, dyslipidemia, hypoglycemia, lactic acidemia, and hyperuricemia are accompanied by neutrophil dysfunction and neutropenia with recurrent infections. 81 The underlying molecular defect is mutation in the gene encoding microsomal glucose-6-phosphate translocase, required for both gluconeogenesis and glycogenolysis. 82 Reduced glucose availability limits the activity of the hexose monophosphate shunt and consequently the generation of NADPH.…”

Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis

“…Interestingly, mutations in the gene that encodes G6PT cause the SCN syndrome glycogen storage disease type Ib, which has variable neutropenia and infections and is associated with systemic complications, such as liver adenomas, growth retardation, osteoporosis, polycystic ovaries, and inflammatory bowel disease. 19 A follow-up report has described a 13th G6PC3-deficient SCN patient, a Moroccan child, with a similar syndrome associated with a novel nonsense G6PC3 mutation designated 115X. 20 A lack of bone marrow neutrophils was reported in 4 patients in the Boztug et al series (all homozygous for the mutation G6PC3 R253H) and in the patient with 115X.…”