Involvement of endocrine system in a patient affected by Glycogen storage disease 1b: speculation on the role of autoimmunity

Daniela Melis,Alessandro Rossi,Giorgia Minopoli,Francesca Balivo,Mariacarolina Salerno,Roberto Della Casa,Generoso Andria,Giancarlo Parenti

doi:10.1186/1824-7288-40-30

Daniela Melis, Alessandro Rossi + Show 6 more

Open Access

https://doi.org/10.1186/1824-7288-40-30

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Abstract

Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

Highlights

Glycogen storage disease type 1b (GSD1b; OMIM 232220) is an inherited metabolic defect due to mutations of the SLC37A4 gene that encodes a microsomal glucose-6phosphate transporter (G6PT) [1]
We report on a patient presenting with different manifestations related to altered immune response, such as increased susceptibility to bacterial infections, autoimmune thyroiditis and autoimmune growth hormone (GH) deficiency
The occurrence of autoimmune disorders has been reported in GSD1b only in the recent years and little is known about its pathophysiology

Summary

Background

Glycogen storage disease type 1b (GSD1b; OMIM 232220) is an inherited metabolic defect due to mutations of the SLC37A4 gene that encodes a microsomal glucose-6phosphate transporter (G6PT) [1]. In addition to the classical phenotype of glycogenoses, GSD1b is associated with neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections, aphthous stomatitis, and inflammatory bowel disease (IBD) [4,5]. These manifestations are highly debilitating and impact significantly on patients’ quality of life, their pathophysiology is still poorly characterized. Recurrent respiratory and gastro-intestinal infections and splenomegaly were recorded When he was 8 years old, glomerular hyperfiltration and microalbuminuria were detected on routine biochemical evaluations and treatment with ACE-inhibitors was started to prevent further progression of renal disease. A dynamic low dose ACTH test was performed showing a significant increase in cortisol levels (cortisol T0 51.1 ng/ml, T30 221 ng/ml, T60 229 ng/ml, T90 260 ng/ml), suggesting a normal functioning of the adrenal gland and only a slight pituitary dysfunction

Conclusions

Findings

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