Original Articles
Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: Results of the European Study on Glycogen Storage Disease Type I,☆☆

https://doi.org/10.1067/mpd.2000.105232Get rights and content

Abstract

Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in 12 European countries that included all patients with GSD-I who were known at the centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I, 57 who had GSD-Ib form the basis of this study. Results: Neutropenia (defined as an absolute neutrophil count <1 × 109/L) was found in 54 patients. In 64% of the patients neutropenia was documented before the age of 1 year, but in 18% of the patients neutropenia was first noted between the ages of 6 and 9 years. Neutropenia was persistent in 5 patients and intermittent without any clear cyclical course in 45. Neutrophil function was investigated in 18 patients with neutropenia and was abnormal in all. Perioral infections were reported in 37 patients, perianal infections in 27 patients, and protracted diarrhea in 23 patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients suspected to have IBD were abnormal in all. All patients with IBD, perioral infections, and perianal infections had neutropenia. Conclusions: Intermittent severe neutropenia is frequently found in patients with GSD-Ib. The study also indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied had evidence of IBD, all of whom had neutropenia. IBD was not detected in those with normal neutrophil counts. These findings support the notion that neutropenia and/or neutrophil dysfunction in GSD-Ib and IBD are causally related. (J Pediatr 2000;137:187-91)

Section snippets

Methods

Patients were identified from hospital records of 16 metabolic centers in 12 European countries. Patients were coded by initials and date of birth to check for duplication. Retrospective patient records were discussed in a multicenter meeting and filled in by either the treating physician or by one of the investigators (J.P.R.). All known patients in the participating centers born after 1960 were included.

The diagnosis of GSD-Ib was made either with enzyme studies that showed the combination of

Results

The European study on GSD-I recorded details of 296 patients with GSD-I, among whom 65 were reported to have GSD-Ib. Of those 65, 8 patients were excluded because the enzyme studies were incomplete or unreliable. Details of the entire cohort will be described elsewhere, but none of the patients with GSD-Ia had documented neutropenia or neutrophil dysfunction.

The patients with GSD-Ib (30 male and 27 female) were born between 1964 and 1995; 49 are alive. The median age when data were collected

Discussion

In a large retrospective case study of patients with GSD-I older then 18 years of age, dead or alive, throughout the United States and Canada, Talente et al22 reported only 5 patients with GSD-Ib. These patients had a mean age of 21.8 years and represented 13.5% of patients in the study. In this retrospective multicenter study a large cohort of patients with GSD-Ib of all ages was studied. This could explain the higher percentage of patients with GSD-Ib (19.8% of all patients with GSD-I),

Acknowledgements

Participating centers: Austria: Prof W. Endres, Dr D. Skladal, Innsbruck; Belgium: Dr E. Sokal, Brussels; Czech Republic: Dr J. Zeman, Prague; France: Prof P. H. Labrune, Clamart; Germany: Dr P. Bührdel, Leipzig, Prof K. Ulrich, Hamburg, Prof U. Wendell, Düsseldorf; Great Britain: Prof J. V. Leonard, Dr P. Lee, London; Hungary: Dr L. Szönyi, Budapest; Italy: Dr P. Gandullia, Prof R. Gatti, Dr M. di Rocco, Genova, Prof G. Andria, Dr D. Melis, Napoli, Israel: Prof S. Moses, Beersheva; Poland:

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    Supported in part by grants from Amgen, Breda, The Netherlands, and SHS Gesellschaft für klinische Ernährung mbH, Heilbronn, Germany.

    ☆☆

    Reprint requests: G. Visser, Beatrix Children's Hospital, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

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