Infectious and digestive complications in glycogen storage disease type Ib: Study of a French cohort

Camille Wicker; Célina Roda; Ariane Perry; Jean Baptiste Arnoux; Anais Brassier; Martin Castelle; Aude Servais; Jean Donadieu; Juliette Bouchereau; Bénédicte Pigneur; Philippe Labrune; Frank M Ruemmele; Pascale de Lonlay

doi:10.1016/j.ymgmr.2020.100581

Infectious and digestive complications in glycogen storage disease type Ib: Study of a French cohort

Mol Genet Metab Rep. 2020 Apr 9:23:100581. doi: 10.1016/j.ymgmr.2020.100581. eCollection 2020 Jun.

Authors

Camille Wicker¹, Célina Roda², Ariane Perry^{3

4}, Jean Baptiste Arnoux¹, Anais Brassier¹, Martin Castelle⁵, Aude Servais¹, Jean Donadieu⁶, Juliette Bouchereau^{1

7}, Bénédicte Pigneur⁸, Philippe Labrune^{3

4}, Frank M Ruemmele^{8

7

9}, Pascale de Lonlay^{1

7

9

10}

Affiliations

¹ Reference Center for Inherited Metabolic Diseases, Necker Hospital, APHP, Filière G2 M, MetabERN, Paris, France.
² Paris University, CRESS, HERA (Health Environmental Risk Assessment) team, INSERM, INRA, F-75004 Paris, France.
³ Reference Center for Inherited Metabolic Diseases, Antoine Béclère Hospital, APHP, Filière G2M, MetabERN, Clamart, France.
⁴ Paris Sud University, Paris Saclay, and INSERM, U 1995, France.
⁵ Hematology, Necker Hospital, APHP, Paris Descartes University, Paris, France.
⁶ Hematology Department, Trousseau Hospital, APHP, Paris, France.
⁷ Paris Descartes University- Sorbonne Paris Cité, Paris Faculty of Medecine, Paris, France.
⁸ Paediatric Gastroentérology Department, Necker Hospital, APHP, Paris, France.
⁹ Institut Imagine, INSERM U 1163, Paris, France.
¹⁰ Institut Necker Enfants Malades, INSERM, Unit 1151, Paris, France.

Abstract

Glycogenosis type Ib (GSD1B) causes not only hypoglycemia but also infections and "Crohn's disease like" inflammatory bowel disease (IBD) that can significantly impair patient's quality of life. We retrospectively evaluated infectious and digestive complications in 9 French patients (3 girls, 6 boys) diagnosed at 0.8 years on average, with a mean follow-up of 19.1 years. Infections occurred earlier than IBD, at mean ages of 1.7 and 3.8 years, respectively. The number of acute hospitalizations was 0.7/year due to infectious (0.4/year) or digestive symptoms (0.4/year). Clinical presentations allowed separating patients into mild (n = 5) and severe (n = 4) intestinal involvement. Patients in the severe group had more serious digestive symptoms but also earlier neutropenia (median 0.3 vs. 1.5 years, p =0 .046) with a tendency to a lower neutrophil count (NC) during follow-up, and a higher number of acute hospitalizations (median 1.3/year vs. 0.2/year, p =0 .014) due to digestive symptoms (median 0.6/year vs. 0.05/year, p = 0,012) and infections (median 0.8/year vs. 0.2/year, p =0 .014). Treatments included G-CSF and cotrimoxazole (n = 7), 5-aminosalicylic acid (n = 2), and a polymeric solution enriched in the anti-inflammatory cytokine TGF-β (n = 4, "severe" group), and immunomodulatory treatment (n = 1). In conclusion, infections and IBD are rare but severe complications in GSD1B. Neutropenia tended to be more prevalent in the severe IBD group than in the mild IBD group. Dietetic treatment with specific anti-inflammatory solutions seems particularly appropriate in these patients.

Keywords: ANC, Absolute Neutrophil Count; Anti-inflammatory solutions; CD, Crohn's disease; CRP, C-reactive protein; EEN, Exclusive Enteral Nutrition; EN, Enteral Nutrition; ENT, Ear, Nose and Throat; ESR, erythrocyte sedimentation rate; G-CSF, Granulocyte colony-stimulating factor; G6PT, glucose-6-phosphate translocase; GSD1, Glycogen storage disease type I; Glycogen storage disease type 1B; Harvey Bradshaw score; IBD, Inflammatory Bowel Disease; Inflammatory bowel disease; Neutropenia; PEN, Partial Enteral Nutrition; SD, Standard Deviation.