Background Inflammatory bowel disease (IBD)-like conditions in glycogen
storage disease (GSD) type Ib have been predominantly described in children.
Signs and symptoms of GSD type Ib are hypoglycemia, pancytopenia and
hepatosplenomegaly. Based on few published cases, there is evidence that
granulocyte-colony stimulating factor (G-CSF) in patients with
glycogenosis–related pancytopenia might ameliorate the IBD-like disease
through leukocyte increase. Case presentation Here we firstly describe a case
of an adult 33-year-old Caucasian male patient with GSD type Ib accompanied
with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF
treatment. Recent vomiting and abdominal discomfort were due to a high-grade
stenosis in the transverse colon. A dose increase of the G-CSF successfully
normalized his leukocyte count. However, the stenosis worsened and surgical
therapy was needed. Conclusion We suggest that symptomatic patients with GSD
type Ib should undergo endoscopic examination in order to detect IBD-like
disease and to initiate early treatment

Britta Siegmund

Christoph Treese

Hans-Jörg Epple

Magdalena Sarah Volz

Mani Nassir

Moritz von Winterfeld

Ursula Plöckinger

BMC Gastroenterology

PubMed

Volz, Magdalena Sarah

Nassir, Mani

Treese, Christoph

Winterfeld, Moritz von

Plöckinger, Ursula

Epple, Hans-Jörg

Institutional Repository of the Freie Universität Berlin

Volz et al. BMC Gastroenterology  (2015) 15:45 DOI 10.1186/s12876-015-0271-9CASE REPORT Open AccessInflammatory bowel disease (IBD)-like disease in acase of a 33-year old man with glycogenosis 1bMagdalena Sarah Volz1†, Mani Nassir1†, Christoph Treese1, Moritz von Winterfeld2, Ursula Plöckinger3,Hans-Jörg Epple1 and Britta Siegmund1*AbstractBackground: Inflammatory bowel disease (IBD)-like conditions in glycogen storage disease (GSD) type Ib havebeen predominantly described in children. Signs and symptoms of GSD type Ib are hypoglycemia, pancytopeniaand hepatosplenomegaly. Based on few published cases, there is evidence that granulocyte-colony stimulatingfactor (G-CSF) in patients with glycogenosis–related pancytopenia might ameliorate the IBD-like disease throughleukocyte increase.Case presentation: Here we firstly describe a case of an adult 33-year-old Caucasian male patient with GSD type Ibaccompanied with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF treatment. Recentvomiting and abdominal discomfort were due to a high-grade stenosis in the transverse colon. A dose increase ofthe G-CSF successfully normalized his leukocyte count. However, the stenosis worsened and surgical therapy wasneeded.Conclusion: We suggest that symptomatic patients with GSD type Ib should undergo endoscopic examination inorder to detect IBD-like disease and to initiate early treatment.Keywords: Crohn’s disease, IBD-like disease, Stenosis, Glycogenosis, Glycogen storage disease, Granulocyte colonystimulating factor, G-CSFBackgroundGlycogen storage disease Ib (GSD Ib) is characterizedby deficiency of glucose-6-phosphate translocase (Gene:SLC37A4) [1] inherited as an autosomal recessive trait.Clinically the disease is characterized by deficient glyco-genolysis resulting in hypoglycemia, hypertriglyceridemia,phosphate deficiency and lactate acidosis and hepatosple-nomegaly. Pancytopenia may occur with GSD Ib [2]. Sofar, inflammatory bowel disease (IBD)-like conditions hasbeen predominantly described in children with GSD Ibwith mean age of approximately 5.9 years [3-5]. This casereports of an adult 33-year-old man.Case presentationHere we report a 33-year-old Caucasian man with GSDIb presented at our emergency room complaining of* Correspondence: britta.siegmund@charite.de†Equal contributors1Department of Medicine I (Gastroenterology, Rheumatology, InfectiousDiseases), Charité – Universitätsmedizin Berlin, Berlin, GermanyFull list of author information is available at the end of the article© 2015 Volz et al.; licensee BioMed Central. ThCommons Attribution License (http://creativecreproduction in any medium, provided the orDedication waiver (http://creativecommons.orunless otherwise stated.abdominal pain, nausea and vomiting. Onset of symptomswas acute. The patient reported not to know similarconditions before except diffuse pain due to hypoglycemia,which he described differently. The patient had an irregularheterozygous compound gene mutation (c.[1108_1109delCT(;)1189 + 1G > C]; protein level: p.[Leuc370Valfs*53(;)];in exons 10), suggestive to be disease relevant. Noother family member suffered from GSD. He reportedregular defecation of mushy consistency without bloodthree times a day. Physical examination revealed in spiteof pronounced hepatomegaly and cachexia, normal oraland anal mucosa as well as normal height and intelligence(occupation: sales representative in the IT industry).Despite regular cornstarch ingestion of 90 g/every 4 h, theglucose concentration at first presentation was 34 mg/dl,lactate concentration was 134 mg/dl (ULN = 20 mg/dl),and C-reactive protein was 13.5 mg/l (ULN= 5 mg/l).Even though the patient was on continuous granulocytecolony stimulating factor (G-CSF) therapy (48 millionIU/every other day) leukopenia prevailed (leukocytes0.93/nl, neutrophils 0.76/nl, hemoglobin 10.0 g/dl,is is an Open Access article distributed under the terms of the Creativeommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andiginal work is properly credited. The Creative Commons Public Domaing/publicdomain/zero/1.0/) applies to the data made available in this article,Volz et al. BMC Gastroenterology  (2015) 15:45 Page 2 of 4thrombocytes 125/nl). Initially intravenous glucose in-fusion improved his abdominal symptoms. A diagnosticCT-scan to exclude ischemia demonstrated hepatospleno-megaly, a feature of GSD Ib, and a short thickening of theintestinal wall at the transverse colon (Figure 1A and B).Ultrasound examination of the abdomen confirmedthe stenosis. At the location of the stenosis the entireintestinal wall was 6 mm in diameter. There was nointestinal wall vascularization, consistent with grade Iof IBD according to the Limberg classification [6](Figure 1C). A colonoscopy again revealed a shortstenosis in the transverse colon which could not bepassed with a 12.8 mm colonoscope (Figure 2A). Thestenosis appeared scarred with some inflammatory changes.Histopathological examination of the biopsy showedhyperplastic and polypoid mucosa. Gastroscopy of theupper gastrointestinal tract was without pathologies. Dueto the severe leukopenia/neutropenia, immunosuppressivemedication, such as steroids or TNF-alpha antibodies,was not considered a treatment option. Instead, weincreased the dosage of G-CSF to 30 million IU/d inorder to reach a higher leukocyte count and thus, tocontrol the mucosal inflammation. The decision wasbased on evidence for a beneficial effect of G-CSF inA BCFigure 1 Radiographic pictures of the stenosis. 1A and 1B: CT-scan ofview). 1C: Ultrasound picture of the stenosis. Stenosis was 5.9 mm × 6.7 mThere was no intra- or extra-mural vascularization present consistent with lglycogenosis-associated IBD-like disease [3] as well as aprevious randomized controlled trial in patients withCrohn’s disease showing that GM-CSF was able todecrease disease activity and to improve quality of life [7].After five weeks on high-dose G-CSF abdominal painhad receded, yet defecation was still mushy. Leucocytes hadnormalized (5-7/nl), while anemia and thrombocytopeniapersisted (hemoglobin: 11.8 g/dl (LLN= 13.5 g/dl); throm-bocytes: 84/nl (LLN= 150/nl)). C-reactive protein (0.7 mg/l)was normal as was calprotectin (<50 mg/kg). However,colonoscopy revealed a progressive, predominantlyscarring stenosis with approximately 4 mm in diameter(Figure 2B). Thus, surgical therapy was decided upon.A laparoscopic segmental resection of the transversecolon with end-to-end-anastomosis was performed.The instantaneous section showed chronic, florid ulcerousinflammation, hypertrophic muscular layer and massivefibrosis consistent with a scarring stenosis. No signs ofmalignancy were observed (Figure 3). Surgery wascomplicated by insufficiency of the anastomosisresulting in an intra-abdominal abscess and subsequentsurgery. Eighteen days after the second surgery thepatient could be discharged from the hospital on hisformer G-CSF schedule.the stenosis of the transverse colon (1A: frontal view; 1B: horizontalm in diameter. The intestinal wall appeared thickened and hypoechoic.evel I according to the Limberg classification.Figure 2 Endoscopic pictures of the stenosis. 2A: First colonoscopy with macroscopic inflammation. 2B: Second colonoscopy withincreased stenosis.Volz et al. BMC Gastroenterology  (2015) 15:45 Page 3 of 4DiscussionWe describe a case of an IBD-like disease in an adultpatient with GSD type Ib. This condition is caused by adeficiency of the enzyme glucose-6-phosphate translocaseas well as pancytopenia [1,2]. To the best of ourknowledge, only few cases of IBD-like disease in GSDtype Ib, mainly in children, have been described sofar [5,8-14]. The patient in our case was 33-year-oldbefore he presented symptoms of an IBD-like disease.This might be due to his continuous G-CSF treatment,since neutrophil count has been maintained higher andpotentially delayed onset of IBD-like disease. On theother hand, his irregular heterozygous compoundgene mutation could be an explanation why he gotsymptomatic as an adult and not as a child. Overall,IBD is thought to be associated with GSD type Ib, andleukopenia/neutropenia may play a role in the pathogenesisof intestinal inflammation [5]. This assumption issupported by evidence that colony stimulating factorscan improve IBD-like disease in patients with GSDtype Ib [3,7,15,16]. In a previous report, it was shownthat G(M)-CSF not only increased neutrophil count,but also improved intestinal inflammation as indicatedby radiological findings and clinical symptoms of twoyoung patients with GSD-associated IBD-like disease[15]. The authors suggested that neutrophil deficiencyFigure 3 Histological picture. Pathological picture of instantaneous sectiohypertrophy of the muscular layer and massive fibrosis consistent with a scmight contribute to the development of this phenotype byfacilitating acute and chronic infection in the gut mucosaleading to subsequent inflammation [15]. Alternatively,abnormal bowel metabolism resulting from translocasedeficiency in the mucosal cells may be an explanation. Incontrast to these previous reports, G-CSF did not improvethe IBD-like disease in the present case of an adultpatient suffering from GSD type Ib. Moreover, despitea normalization of leucocytes/neutrophils in responseto the dose increase of G-CSF treatment, his abdominalstenosis worsened. This may be due to i) the fact thatdespite normalization of leukocyte counts, dysfunctionalglucose-6-phosphatase deficient neutrophils are lesseffective in dealing with inflammatory processes [15], ii)the acute inflammatory stage of the IBD-like disease hadalready passed and a mainly scarring stenosis remained,when the patient presented as indicated by the scarredendoscopic and pathologic appearance.ConclusionTherefore, we suggest that even in adult patients withGSD type Ib abdominal symptoms, normally interpreted asrelated to hypoglycemia or lactate acidosis, should includethe differential diagnosis of an IBD-like disease. Immediateabdominal ultrasound examination should be performedfollowed by a colonoscopy in case of pathological findingsn showing chronic, florid ulcerous inflammation as well as aarring stenosis.Volz et al. BMC Gastroenterology  (2015) 15:45 Page 4 of 4in order to detect IBD-like disease in an early stage. Thismay allow appropriate treatment as soon as possible in thecourse of disease and prevent surgical treatment.ConsentWritten informed consent was obtained from the patientfor publication of this Case report and any accompanyingimages. A copy of the written consent is available for reviewby the Editor of this journal. The CARE guidelines havebeen used for this case report [17].AbbreviationsCT: Computer tomography; GSD: Glycogen storage disease; G-CSF:Granulocyte-colony stimulating factor; G(M)-CSF: Granulocyte-macrophagecolony-stimulating factor; IBD: Inflammatory bowel disease; LLN: Lower limit ofnormal; TNF: Tumor necrosis factors; ULN: Upper limit of normal.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsMSV has made substantial contributions to conception, acquisition of data,interpretation of data, and drafting the manuscript. MN has made substantialcontributions to acquisition of data, interpretation of data, and revising themanuscript critically for important intellectual content. CT has madesubstantial contributions to acquisition of data, and revising the manuscriptcritically for important intellectual content. MvW has made substantialcontributions to acquisition of data, and revising the manuscript critically forimportant intellectual content. UP has made substantial contributions toacquisition of data, interpretation of data, and revising the manuscript criticallyfor important intellectual content. H-JE has made substantial contributionsto conception, acquisition of data, interpretation of data, and revising themanuscript critically for important intellectual content. BS has made substantialcontributions to conception, acquisition of data, interpretation of data, andrevising the manuscript critically for important intellectual content. All authorsread and approved the final manuscript.Author details1Department of Medicine I (Gastroenterology, Rheumatology, InfectiousDiseases), Charité – Universitätsmedizin Berlin, Berlin, Germany. 2Institute ofPathology, Charité – Universitätsmedizin Berlin, Berlin, Germany.3Interdisciplinary Center of Metabolism: Endocrinology, Diabetes andMetabolism, Charité – Universitätsmedizin Berlin, Berlin, Germany.Received: 25 January 2015 Accepted: 20 March 2015References1. Kure S, Suzuki Y, Matsubara Y, Sakamoto O, Shintaku H, Isshiki G, et al.Molecular analysis of glycogen storage disease type Ib: identification of aprevalent mutation among Japanese patients and assignment of a putativeglucose-6-phosphate translocase gene to chromosome 11. Biochem BiophysRes Commun. 1998;248(2):426–31.2. Schaub J, Heyne K. Glycogen storage disease type Ib. Eur J Pediatr. 1983;140(4):283–8.3. Alsultan A, Sokol RJ, Lovell MA, Thurman G, Ambruso DR. Long termG-CSF-induced remission of ulcerative colitis-like inflammatory boweldisease in a patient with glycogen storage disease Ib and evaluation ofassociated neutrophil function. Pediatr Blood Cancer. 2010;55(7):1410–3.4. Melis D, Parenti G, Della Casa R, Sibilio M, Berni Canani R, Terrin G, et al.Crohn’s-like ileo-colitis in patients affected by glycogen storage disease Ib:two years’ follow-up of patients with a wide spectrum of gastrointestinalsigns. Acta Paediatr. 2003;92(12):1415–21.5. Roe TF, Thomas DW, Gilsanz V, Isaacs Jr H, Atkinson JB. Inflammatory boweldisease in glycogen storage disease type Ib. J Pediatr. 1986;109(1):55–9.6. Kratzer W, Foeller T, Kaechele V, Reinshagen M, Tirpitz CV, Haenle MM.[Intestinal wall vascularisation in Crohn’s disease]. Z Gastroenterol.2004;42(9):973–8.7. Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ.Sargramostim for active Crohn’s disease. N Engl J Med. 2005;352(21):2193–201.8. Saltik-Temizel IN, Kocak N, Ozen H, Yuce A, Gurakan F, Demir H.Inflammatory bowel disease-like colitis in a young Turkish child with glycogenstorage disease type 1b and elevated platelet count. Turk J Pediatr.2005;47(2):180–2.9. Wendel U, Bremer HJ, Willberg B. Inflammatory bowel disease in glycogenstorage disease type Ib. J Pediatr. 1987;110(1):166.10. Yamaguchi T, Ihara K, Matsumoto T, Tsutsumi Y, Nomura A, Ohga S, et al.Inflammatory bowel disease-like colitis in glycogen storage disease type 1b.Inflamm Bowel Dis. 2001;7(2):128–32.11. Sanderson IR, Bisset WM, Milla PJ, Leonard JV. Chronic inflammatory boweldisease in glycogen storage disease type 1B. J Inherit Metab Dis.1991;14(5):771–6.12. de Parscau L, Maire I, Guibaud P, Gonthier R, Dumollard JM, Rousset H.Glycogen storage disease and inflammatory bowel disease. J Pediatr.1989;115(2):337.13. Schulman H, Weizman Z, Barki Y, Maor E, Hertzanu Y. Inflammatory boweldisease in glycogen storage disease type 1 B. Pediatr Radiol.1995;25 Suppl 1:S160–2.14. Visser G, Rake JP, Fernandes J, Labrune P, Leonard JV, Moses S, et al.Neutropenia, neutrophil dysfunction, and inflammatory bowel disease inglycogen storage disease type Ib: results of the European Study onGlycogen Storage Disease type I. J Pediatr. 2000;137(2):187–91.15. Roe TF, Coates TD, Thomas DW, Miller JH, Gilsanz V. Brief report: treatmentof chronic inflammatory bowel disease in glycogen storage disease type Ibwith colony-stimulating factors. N Engl J Med. 1992;326(25):1666–9.16. Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K, et al.Granulocyte colony-stimulating factor in glycogen storage disease type 1b.Results of the European Study on Glycogen Storage Disease Type 1. Eur JPediatr. 2002;161 Suppl 1:S83–7.17. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. The CAREguidelines: consensus-based clinical case report guideline development.J Clin Epidemiol. 2013;67:46–51.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color ﬁgure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit

Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man
with glycogenosis 1b

Springer - Publisher Connector

Volz et al. BMC Gastroenterology  (2015) 15:45 
DOI 10.1186/s12876-015-0271-9CASE REPORT Open AccessInflammatory bowel disease (IBD)-like disease in a
case of a 33-year old man with glycogenosis 1b
Magdalena Sarah Volz1†, Mani Nassir1†, Christoph Treese1, Moritz von Winterfeld2, Ursula Plöckinger3,
Hans-Jörg Epple1 and Britta Siegmund1*Abstract
Background: Inflammatory bowel disease (IBD)-like conditions in glycogen storage disease (GSD) type Ib have
been predominantly described in children. Signs and symptoms of GSD type Ib are hypoglycemia, pancytopenia
and hepatosplenomegaly. Based on few published cases, there is evidence that granulocyte-colony stimulating
factor (G-CSF) in patients with glycogenosis–related pancytopenia might ameliorate the IBD-like disease through
leukocyte increase.
Case presentation: Here we firstly describe a case of an adult 33-year-old Caucasian male patient with GSD type Ib
accompanied with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF treatment. Recent
vomiting and abdominal discomfort were due to a high-grade stenosis in the transverse colon. A dose increase of
the G-CSF successfully normalized his leukocyte count. However, the stenosis worsened and surgical therapy was
needed.
Conclusion: We suggest that symptomatic patients with GSD type Ib should undergo endoscopic examination in
order to detect IBD-like disease and to initiate early treatment.
Keywords: Crohn’s disease, IBD-like disease, Stenosis, Glycogenosis, Glycogen storage disease, Granulocyte colony
stimulating factor, G-CSFBackground
Glycogen storage disease Ib (GSD Ib) is characterized
by deficiency of glucose-6-phosphate translocase (Gene:
SLC37A4) [1] inherited as an autosomal recessive trait.
Clinically the disease is characterized by deficient glyco-
genolysis resulting in hypoglycemia, hypertriglyceridemia,
phosphate deficiency and lactate acidosis and hepatosple-
nomegaly. Pancytopenia may occur with GSD Ib [2]. So
far, inflammatory bowel disease (IBD)-like conditions has
been predominantly described in children with GSD Ib
with mean age of approximately 5.9 years [3-5]. This case
reports of an adult 33-year-old man.Case presentation
Here we report a 33-year-old Caucasian man with GSD
Ib presented at our emergency room complaining of* Correspondence: britta.siegmund@charite.de
†Equal contributors
1Department of Medicine I (Gastroenterology, Rheumatology, Infectious
Diseases), Charité – Universitätsmedizin Berlin, Berlin, Germany
Full list of author information is available at the end of the article
© 2015 Volz et al.; licensee BioMed Central. Th
Commons Attribution License (http://creativec
reproduction in any medium, provided the or
Dedication waiver (http://creativecommons.or
unless otherwise stated.abdominal pain, nausea and vomiting. Onset of symptoms
was acute. The patient reported not to know similar
conditions before except diffuse pain due to hypoglycemia,
which he described differently. The patient had an irregular
heterozygous compound gene mutation (c.[1108_1109delCT
(;)1189 + 1G > C]; protein level: p.[Leuc370Valfs*53(;)];
in exons 10), suggestive to be disease relevant. No
other family member suffered from GSD. He reported
regular defecation of mushy consistency without blood
three times a day. Physical examination revealed in spite
of pronounced hepatomegaly and cachexia, normal oral
and anal mucosa as well as normal height and intelligence
(occupation: sales representative in the IT industry).
Despite regular cornstarch ingestion of 90 g/every 4 h, the
glucose concentration at first presentation was 34 mg/dl,
lactate concentration was 134 mg/dl (ULN = 20 mg/dl),
and C-reactive protein was 13.5 mg/l (ULN= 5 mg/l).
Even though the patient was on continuous granulocyte
colony stimulating factor (G-CSF) therapy (48 million
IU/every other day) leukopenia prevailed (leukocytes
0.93/nl, neutrophils 0.76/nl, hemoglobin 10.0 g/dl,is is an Open Access article distributed under the terms of the Creative
ommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
iginal work is properly credited. The Creative Commons Public Domain
g/publicdomain/zero/1.0/) applies to the data made available in this article,
Volz et al. BMC Gastroenterology  (2015) 15:45 Page 2 of 4thrombocytes 125/nl). Initially intravenous glucose in-
fusion improved his abdominal symptoms. A diagnostic
CT-scan to exclude ischemia demonstrated hepatospleno-
megaly, a feature of GSD Ib, and a short thickening of the
intestinal wall at the transverse colon (Figure 1A and B).
Ultrasound examination of the abdomen confirmed
the stenosis. At the location of the stenosis the entire
intestinal wall was 6 mm in diameter. There was no
intestinal wall vascularization, consistent with grade I
of IBD according to the Limberg classification [6]
(Figure 1C). A colonoscopy again revealed a short
stenosis in the transverse colon which could not be
passed with a 12.8 mm colonoscope (Figure 2A). The
stenosis appeared scarred with some inflammatory changes.
Histopathological examination of the biopsy showed
hyperplastic and polypoid mucosa. Gastroscopy of the
upper gastrointestinal tract was without pathologies. Due
to the severe leukopenia/neutropenia, immunosuppressive
medication, such as steroids or TNF-alpha antibodies,
was not considered a treatment option. Instead, we
increased the dosage of G-CSF to 30 million IU/d in
order to reach a higher leukocyte count and thus, to
control the mucosal inflammation. The decision was
based on evidence for a beneficial effect of G-CSF inA B
C
Figure 1 Radiographic pictures of the stenosis. 1A and 1B: CT-scan of
view). 1C: Ultrasound picture of the stenosis. Stenosis was 5.9 mm × 6.7 m
There was no intra- or extra-mural vascularization present consistent with lglycogenosis-associated IBD-like disease [3] as well as a
previous randomized controlled trial in patients with
Crohn’s disease showing that GM-CSF was able to
decrease disease activity and to improve quality of life [7].
After five weeks on high-dose G-CSF abdominal pain
had receded, yet defecation was still mushy. Leucocytes had
normalized (5-7/nl), while anemia and thrombocytopenia
persisted (hemoglobin: 11.8 g/dl (LLN= 13.5 g/dl); throm-
bocytes: 84/nl (LLN= 150/nl)). C-reactive protein (0.7 mg/l)
was normal as was calprotectin (<50 mg/kg). However,
colonoscopy revealed a progressive, predominantly
scarring stenosis with approximately 4 mm in diameter
(Figure 2B). Thus, surgical therapy was decided upon.
A laparoscopic segmental resection of the transverse
colon with end-to-end-anastomosis was performed.
The instantaneous section showed chronic, florid ulcerous
inflammation, hypertrophic muscular layer and massive
fibrosis consistent with a scarring stenosis. No signs of
malignancy were observed (Figure 3). Surgery was
complicated by insufficiency of the anastomosis
resulting in an intra-abdominal abscess and subsequent
surgery. Eighteen days after the second surgery the
patient could be discharged from the hospital on his
former G-CSF schedule.the stenosis of the transverse colon (1A: frontal view; 1B: horizontal
m in diameter. The intestinal wall appeared thickened and hypoechoic.
evel I according to the Limberg classification.
Figure 2 Endoscopic pictures of the stenosis. 2A: First colonoscopy with macroscopic inflammation. 2B: Second colonoscopy with
increased stenosis.
Volz et al. BMC Gastroenterology  (2015) 15:45 Page 3 of 4Discussion
We describe a case of an IBD-like disease in an adult
patient with GSD type Ib. This condition is caused by a
deficiency of the enzyme glucose-6-phosphate translocase
as well as pancytopenia [1,2]. To the best of our
knowledge, only few cases of IBD-like disease in GSD
type Ib, mainly in children, have been described so
far [5,8-14]. The patient in our case was 33-year-old
before he presented symptoms of an IBD-like disease.
This might be due to his continuous G-CSF treatment,
since neutrophil count has been maintained higher and
potentially delayed onset of IBD-like disease. On the
other hand, his irregular heterozygous compound
gene mutation could be an explanation why he got
symptomatic as an adult and not as a child. Overall,
IBD is thought to be associated with GSD type Ib, and
leukopenia/neutropenia may play a role in the pathogenesis
of intestinal inflammation [5]. This assumption is
supported by evidence that colony stimulating factors
can improve IBD-like disease in patients with GSD
type Ib [3,7,15,16]. In a previous report, it was shown
that G(M)-CSF not only increased neutrophil count,
but also improved intestinal inflammation as indicated
by radiological findings and clinical symptoms of two
young patients with GSD-associated IBD-like disease
[15]. The authors suggested that neutrophil deficiencyFigure 3 Histological picture. Pathological picture of instantaneous sectio
hypertrophy of the muscular layer and massive fibrosis consistent with a scmight contribute to the development of this phenotype by
facilitating acute and chronic infection in the gut mucosa
leading to subsequent inflammation [15]. Alternatively,
abnormal bowel metabolism resulting from translocase
deficiency in the mucosal cells may be an explanation. In
contrast to these previous reports, G-CSF did not improve
the IBD-like disease in the present case of an adult
patient suffering from GSD type Ib. Moreover, despite
a normalization of leucocytes/neutrophils in response
to the dose increase of G-CSF treatment, his abdominal
stenosis worsened. This may be due to i) the fact that
despite normalization of leukocyte counts, dysfunctional
glucose-6-phosphatase deficient neutrophils are less
effective in dealing with inflammatory processes [15], ii)
the acute inflammatory stage of the IBD-like disease had
already passed and a mainly scarring stenosis remained,
when the patient presented as indicated by the scarred
endoscopic and pathologic appearance.
Conclusion
Therefore, we suggest that even in adult patients with
GSD type Ib abdominal symptoms, normally interpreted as
related to hypoglycemia or lactate acidosis, should include
the differential diagnosis of an IBD-like disease. Immediate
abdominal ultrasound examination should be performed
followed by a colonoscopy in case of pathological findingsn showing chronic, florid ulcerous inflammation as well as a
arring stenosis.
Volz et al. BMC Gastroenterology  (2015) 15:45 Page 4 of 4in order to detect IBD-like disease in an early stage. This
may allow appropriate treatment as soon as possible in the
course of disease and prevent surgical treatment.
Consent
Written informed consent was obtained from the patient
for publication of this Case report and any accompanying
images. A copy of the written consent is available for review
by the Editor of this journal. The CARE guidelines have
been used for this case report [17].
Abbreviations
CT: Computer tomography; GSD: Glycogen storage disease; G-CSF:
Granulocyte-colony stimulating factor; G(M)-CSF: Granulocyte-macrophage
colony-stimulating factor; IBD: Inflammatory bowel disease; LLN: Lower limit of
normal; TNF: Tumor necrosis factors; ULN: Upper limit of normal.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MSV has made substantial contributions to conception, acquisition of data,
interpretation of data, and drafting the manuscript. MN has made substantial
contributions to acquisition of data, interpretation of data, and revising the
manuscript critically for important intellectual content. CT has made
substantial contributions to acquisition of data, and revising the manuscript
critically for important intellectual content. MvW has made substantial
contributions to acquisition of data, and revising the manuscript critically for
important intellectual content. UP has made substantial contributions to
acquisition of data, interpretation of data, and revising the manuscript critically
for important intellectual content. H-JE has made substantial contributions
to conception, acquisition of data, interpretation of data, and revising the
manuscript critically for important intellectual content. BS has made substantial
contributions to conception, acquisition of data, interpretation of data, and
revising the manuscript critically for important intellectual content. All authors
read and approved the final manuscript.
Author details
1Department of Medicine I (Gastroenterology, Rheumatology, Infectious
Diseases), Charité – Universitätsmedizin Berlin, Berlin, Germany. 2Institute of
Pathology, Charité – Universitätsmedizin Berlin, Berlin, Germany.
3Interdisciplinary Center of Metabolism: Endocrinology, Diabetes and
Metabolism, Charité – Universitätsmedizin Berlin, Berlin, Germany.
Received: 25 January 2015 Accepted: 20 March 2015
References
1. Kure S, Suzuki Y, Matsubara Y, Sakamoto O, Shintaku H, Isshiki G, et al.
Molecular analysis of glycogen storage disease type Ib: identification of a
prevalent mutation among Japanese patients and assignment of a putative
glucose-6-phosphate translocase gene to chromosome 11. Biochem Biophys
Res Commun. 1998;248(2):426–31.
2. Schaub J, Heyne K. Glycogen storage disease type Ib. Eur J Pediatr. 1983;140
(4):283–8.
3. Alsultan A, Sokol RJ, Lovell MA, Thurman G, Ambruso DR. Long term
G-CSF-induced remission of ulcerative colitis-like inflammatory bowel
disease in a patient with glycogen storage disease Ib and evaluation of
associated neutrophil function. Pediatr Blood Cancer. 2010;55(7):1410–3.
4. Melis D, Parenti G, Della Casa R, Sibilio M, Berni Canani R, Terrin G, et al.
Crohn’s-like ileo-colitis in patients affected by glycogen storage disease Ib:
two years’ follow-up of patients with a wide spectrum of gastrointestinal
signs. Acta Paediatr. 2003;92(12):1415–21.
5. Roe TF, Thomas DW, Gilsanz V, Isaacs Jr H, Atkinson JB. Inflammatory bowel
disease in glycogen storage disease type Ib. J Pediatr. 1986;109(1):55–9.
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Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b

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Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b

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