JPGN Journal of Pediatric Gastroenterology and Nutrition Publish Ahead of Print DOI : 10.1097/MPG.0000000000000592
Inflammatory Bowel Disease in Glycogen Storage Disease Type Ia: A Case Series Nicole T. Lawrence, MD1, Tayoot Chengsupanimit, BS2, Laurie M. Brown, BS2, Terry G. J. Derks, MD, PhD3, G. Peter A. Smit, MD, PhD3 and David A. Weinstein, MD, MMSc2
1
Division of Pediatric Gastroenterology, Department of Pediatrics, University of Florida College
of Medicine, Gainesville, FL 2
Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of
Pediatrics, University of Florida College of Medicine, Gainesville, FL 3
Department of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands
Address correspondence to: David A. Weinstein, MD, MMSc Director, Glycogen Storage Disease Program Professor, Division of Pediatric Endocrinology University of Florida College of Medicine Box 100296 Gainesville, FL 32610-0296 [email protected] (352) 273-5823
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Abbreviations: GSD, glycogen storage disease; IBD, inflammatory bowel disease; CRP, Creactive protein; ESR, erythrocyte sedimentation rate; AAT, alpha-1-antitrypsin; UC, ulcerative colitis; CD, Crohn disease; ASA, aminosalicylic acid; 6-MP, mercaptopurine; EGD, esophagogastroduodenoscopy
Funding Source: This research was supported by philanthropic support provided by the following funds managed through the University of Florida Office of Development: Scott Miller GSD Program Fund and the GSD Dream Fund. Support for this project was also provided in part by the National Institutes of Health and National Center for Research Resources CTSA grants 1UL1RR029890 (University of Florida).
Financial Disclosure: The authors have no financial relationships relevant to this article to disclose.
Conflict of Interest: The authors have no conflicts of interest to disclose.
Word Count: 1370
Tables: 2
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Introduction: Glycogen storage disease (GSD) type I is an autosomal recessive disorder of glycogen metabolism that affects 1 in 100,000 live births (1). The disorder is caused by mutations in genes that encode for glucose-6-phosphatase [type Ia] and glucose-6-phosphate (G6P) translocase [type Ib] (2). Complications of GSD are difficulty maintaining glucose homeostasis, renal disease, hepatic adenomas, hypertriglyceridemia, hyperlactatemia and hyperuricemia. Neutrophil dysfunction, in GSD Ib, differentiates the subtypes.
Since the mid 1970’s, reports have linked the defect in glucose-6-phosphate translocase function with inflammatory bowel disease (IBD). In 1978, Narisawa et al. described IBD in one patient with GSD I, but subtyping was not available (3). Other case reports followed but have been in reference to the GSD Ib population. Impaired neutrophil function is the proposed cause for the development of IBD in that population (4).
Visser et al. reported worsening diarrhea in GSD I patients of both subtypes; however, the mechanism in GSD Ia patients remains unexplained (5). In a previous study, eighteen GSD Ia patients with diarrhea were evaluated with colonoscopy and fecal alpha-1-antitrypsin (AAT), with nonspecific colonic inflammation noted on histology and AAT within normal limits (5). Currently, a characterization of IBD in genetically proven GSD Ia does not exist.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Case Reports: Patient 1 The patient presented at 7 months of age with hypoglycemia, hepatomegaly, failure to thrive and diarrhea. Management was with continuous gastrointestinal feeds until cornstarch was introduced at 13 years of age. During follow-up visits, the patient reported up to ten loose stools per day. At 25 years of age, the patient began to experience hematochezia and was evaluated with endoscopy. During the colonoscopy, decreased vascularity and ulcerations were noted in the descending and sigmoid colon. Histology was significant for chronic inflammation. While a diagnosis of ulcerative colitis (UC) was not made until a second colonoscopy was performed at 27 years of age, treatment was commenced following the initial colonoscopy. The second procedure was performed due to persistence of the patient’s symptoms. At 43 years of age, the patient complained of abdominal pain and experienced anemia-related fatigue. Treatment has been with aminosalicylic acid (ASA) derivatives and the complaints resolved.
Patient 2 The patient was diagnosed with GSD Ia after presenting with vomiting, hepatomegaly, growth retardation, metabolic acidosis and psychomotor retardation. Frequent gastrointestinal feeds were utilized until daytime cornstarch was introduced at 12 years of age. One year after the initiation of nocturnal cornstarch, the patient complained of abdominal pain and diarrhea. Symptoms persisted despite treatment with mesalamine therapy until cornstarch was discontinued after 8 years of therapy. At 25 years of age, a colonoscopy was performed to evaluate recurrent bloody diarrhea. Visual inspection was normal, but histology was significant for mild and nonspecific
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
pancolitis. At that time, gastrointestinal feeds were reinitiated. All complaints resolved except intermittent episodes of brief rectal bleeding which is attributed to rectal prolapse.
Patient 3 The patient was diagnosed with GSD Ia at 3 months of age. Treatment consisted of continuous nasogastric feeds until transitioning to cornstarch at 42 months of age. At 14 years of age, a CT scan was performed secondary to acute onset abdominal pain. Findings raised concern for appendicitis and laparoscopy was performed. Inflammation of the terminal ileum was noted and then resected. The diagnosis of Crohn disease (CD) was made on histology of the specimen. The post-operative therapeutic regimen consisted of multiple ASAs. Due to a history of severe exacerbations, mercaptopurine (6-MP) and infliximab were added to her regimen. She has since transitioned to chronic therapy with 6-MP and mesalamine. While symptoms have improved, the patient continues to have episodes of abdominal pain and diarrhea approximately once every month.
Patient 4 The patient was diagnosed with GSD Ia at 5 months of age after presenting with failure to thrive, hepatomegaly and developmental delay. Treatment was overnight nasogastric feeds until the transition to cornstarch at 15 years of age. At 42 years old, the patient developed recurrent abdominal pain and diarrhea. An abdominal CT was suggestive of diffuse colitis. Two colonoscopies were performed when the patient was 45 years of age and showed mild active colitis at the terminal ileal valve, ascending and descending colon. A serologic screen for IBD was performed and consistent with CD. Therapy has consisted of multiple ASAs and anti-
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
motility medications. The patient had improved consistency of stools and fewer complaints of abdominal pain.
Patient 5 At 7 months of age, the patient was diagnosed with GSD Ia. Treatment was with continuous nasogastric feeds until 3 years of age. By 9 years of age, cornstarch was the only therapy. At the age of 18, an esophagogastroduodenoscopy (EGD) and colonoscopy were performed to evaluate complaints of abdominal pain, hematochezia and diarrhea. Histology was significant for chronic inflammation. The patient was diagnosed with UC. Treatment was escalated from an ASA to an immune modulator due to continued symptoms.
Discussion: The management of GSD has markedly improved over the past 40 years. Survival was rare prior to the 1970’s and most patients are now doing well into adulthood (6). With aging, long-term complications are appreciated, including the development of hepatic adenomas, hepatocellular carcinomas and hepcidin-induced anemia (6). IBD may be a new complication of the adult population with GSD Ia. Unlike most other complications, however, it appears to be unrelated to metabolic control since all of the afflicted patients had outstanding metabolic control at the time of diagnosis.
While an association between GSD Ib and IBD is well recognized, there are few reports focusing on the presence of diarrhea in GSD Ia, and none has linked this symptom to IBD. In this report, we presented five patients with enzymatically confirmed GSD Ia and endoscopically proven IBD
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
(two with CD and three with UC). The clinical and biochemical characteristics are presented (Tables 1 and 2). An additional four adult patients in our population are suspected to have IBD based on symptoms, inflammatory markers and serologic testing, but they were not included since histologic evidence is unavailable. The prevalence of symptomatic IBD in adults with GSD Ia followed at the University of Florida GSD program is 8.3% in contrast to the prevalence rate of IBD in adults in the United States which is reported to be 908 per 100,000 persons, or 0.9% (7).
In contrast to IBD found in the GSD Ib population, the patients with GSD Ia are developing this complication as adults. Colonic disease is also more common in GSD Ia while IBD in GSD Ib is almost exclusively limited to the small intestine (8). The IBD in GSD Ia also appears to be different from the general population since most go into remission with only ASA treatment. We suspect that IBD in GSD I may be caused by chronic uncooked cornstarch therapy, which could be altering the microbiota of the gastrointestinal tract, but further studies are needed to clarify the pathogenesis of this newly recognized complication.
At this time, we do not yet recommend screening procedures for IBD to be performed in the GSD Ia population in the absence of symptoms until further research can help clarify the cause of IBD development. If the patient starts to experience gastrointestinal abnormalities, then a serological panel or endoscopic procedure may be warranted in the case of persistent symptoms.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Conclusions: With improved survival of GSD patients, new co-morbidities are being recognized. The discovery of IBD in both subtypes of GSD I may provide valuable clues for understanding the development of IBD beyond this population. In general, there is no consensus regarding the pathophysiology of IBD. A complex interplay between genetic predisposition, impaired innate immunity, dysbiosis and environmental factors has been proposed. Future studies are warranted, and physicians should be aware of the possible association with GSD Ia.
Acknowledgements: This research was supported by philanthropic support provided by the following funds managed through the University Of Florida Office Of Development: Scott Miller GSD Program Fund and the GSD Dream Fund. Support for this project was also provided in part by the National Institutes of Health and National Center for Research Resources CTSA grants 1UL1RR029890 (University of Florida). The authors appreciate critical reading of an earlier version of the manuscript by Frank Hoentjen, MD, PhD (Radboud University Medical Center, Nijmegen, The Netherlands) and John E. Simmons, PhD (Trinity College, CT).
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
References: 1. Chen Y-T, Burchell A. Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease, 8th edition. New York: McGraw-Hill; 2001.
2. Lei KJ, Shelly LL, Lin B, et al. Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c.. J Clin Invest 1995;95(1):234-40.
3. Narisawa K, Igarashi Y, Otomo H, et al. A new variant of glycogen storage disease type I probably due to a defect in the glucose-6-phosphate transport system. Biochem Biophys Res Commun 1978;83(4): 1360-4.
4. Visser G, Rake JP, Fernandes J, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I. J Pediatr 2000;137:187-91.
5. Visser G, Rake JP, Kokke FT, et al. Intestinal function in glycogen storage disease type I. J Inherit Metab Dis 2002;25(4):261-7.
6. Weinstein DA, Wolfsdorf JI. Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease. Eur J Pediatr 2002;161 Suppl 1:S35-9.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
7. Nguyen GC, Chong CA, Chong RY. National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States. J Crohns Colitis 2014;8(4):288-95.
8. Davis MK, Valentine JF, Weinstein DA, Polyak S. Antibodies to CBir1 are associated with glycogen storage disease type Ib. J Pediatr Gastroenterol Nutr 2010;51(1):14-8.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Table 1. Clinical characteristics of patients at time of IBD diagnosis Patient 1 2 Sex F M
3 F
4 M
5 M
Age of diagnosis of GSD Ia (months) Mutation Adenomas Triglycerides (mg/dL) Uric Acid (mg/dL) Proteinuria (g/L)
3 R83C/R83C Yes 311 4 None
5 R83C/Q347X Yes 336 8 None
7 R83C/R83C None 124 4 None
7 W63X/V338F Yes 88 4 None
9 175delGG/866delA None 90 4 0.2
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Table 2. IBD characteristics and history of patients Patient 1 2
3
4
5
Age of diagnosis of IBD (years)
Symptoms
27
24
11
42
18
Hematochezia
Abdominal cramping and diarrhea
Abdominal pain and diarrhea
Abdominal pain and diarrhea
Abdominal pain, diarrhea and hematochezia
Resected tissue and colonoscopy
Colonoscopy
Colonoscopy
Ascending and transverse colon Crohn Disease 7 N/A
Pancolonic Ulcerative Colitis 58 N/A
Mesalamine
Mesalamine then infliximab
Endoscopy
Colonoscopy
Colonoscopy
Location of disease Prometheus Panel ESR at diagnosis (mm/hr) Calprotectin (mg/kg)
Pancolonic None N/A 305
Pancolonic None N/A N/A
Treatment
Mesalamine
Mesalamine
Ileal None 81 N/A Mesalamine then mercaptopurine, infliximab and mesalamine
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Inflammatory Bowel Disease in Glycogen Storage Disease Type Ia: A Case Series Nicole T. Lawrence, MD1, Tayoot Chengsupanimit, BS2, Laurie M. Brown, BS2, Terry G. J. Derks, MD, PhD3, G. Peter A. Smit, MD, PhD3 and David A. Weinstein, MD, MMSc2
1
Division of Pediatric Gastroenterology, Department of Pediatrics, University of Florida College
of Medicine, Gainesville, FL 2
Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of
Pediatrics, University of Florida College of Medicine, Gainesville, FL 3
Department of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands
Address correspondence to: David A. Weinstein, MD, MMSc Director, Glycogen Storage Disease Program Professor, Division of Pediatric Endocrinology University of Florida College of Medicine Box 100296 Gainesville, FL 32610-0296 [email protected] (352) 273-5823
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Abbreviations: GSD, glycogen storage disease; IBD, inflammatory bowel disease; CRP, Creactive protein; ESR, erythrocyte sedimentation rate; AAT, alpha-1-antitrypsin; UC, ulcerative colitis; CD, Crohn disease; ASA, aminosalicylic acid; 6-MP, mercaptopurine; EGD, esophagogastroduodenoscopy
Funding Source: This research was supported by philanthropic support provided by the following funds managed through the University of Florida Office of Development: Scott Miller GSD Program Fund and the GSD Dream Fund. Support for this project was also provided in part by the National Institutes of Health and National Center for Research Resources CTSA grants 1UL1RR029890 (University of Florida).
Financial Disclosure: The authors have no financial relationships relevant to this article to disclose.
Conflict of Interest: The authors have no conflicts of interest to disclose.
Word Count: 1370
Tables: 2
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Introduction: Glycogen storage disease (GSD) type I is an autosomal recessive disorder of glycogen metabolism that affects 1 in 100,000 live births (1). The disorder is caused by mutations in genes that encode for glucose-6-phosphatase [type Ia] and glucose-6-phosphate (G6P) translocase [type Ib] (2). Complications of GSD are difficulty maintaining glucose homeostasis, renal disease, hepatic adenomas, hypertriglyceridemia, hyperlactatemia and hyperuricemia. Neutrophil dysfunction, in GSD Ib, differentiates the subtypes.
Since the mid 1970’s, reports have linked the defect in glucose-6-phosphate translocase function with inflammatory bowel disease (IBD). In 1978, Narisawa et al. described IBD in one patient with GSD I, but subtyping was not available (3). Other case reports followed but have been in reference to the GSD Ib population. Impaired neutrophil function is the proposed cause for the development of IBD in that population (4).
Visser et al. reported worsening diarrhea in GSD I patients of both subtypes; however, the mechanism in GSD Ia patients remains unexplained (5). In a previous study, eighteen GSD Ia patients with diarrhea were evaluated with colonoscopy and fecal alpha-1-antitrypsin (AAT), with nonspecific colonic inflammation noted on histology and AAT within normal limits (5). Currently, a characterization of IBD in genetically proven GSD Ia does not exist.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Case Reports: Patient 1 The patient presented at 7 months of age with hypoglycemia, hepatomegaly, failure to thrive and diarrhea. Management was with continuous gastrointestinal feeds until cornstarch was introduced at 13 years of age. During follow-up visits, the patient reported up to ten loose stools per day. At 25 years of age, the patient began to experience hematochezia and was evaluated with endoscopy. During the colonoscopy, decreased vascularity and ulcerations were noted in the descending and sigmoid colon. Histology was significant for chronic inflammation. While a diagnosis of ulcerative colitis (UC) was not made until a second colonoscopy was performed at 27 years of age, treatment was commenced following the initial colonoscopy. The second procedure was performed due to persistence of the patient’s symptoms. At 43 years of age, the patient complained of abdominal pain and experienced anemia-related fatigue. Treatment has been with aminosalicylic acid (ASA) derivatives and the complaints resolved.
Patient 2 The patient was diagnosed with GSD Ia after presenting with vomiting, hepatomegaly, growth retardation, metabolic acidosis and psychomotor retardation. Frequent gastrointestinal feeds were utilized until daytime cornstarch was introduced at 12 years of age. One year after the initiation of nocturnal cornstarch, the patient complained of abdominal pain and diarrhea. Symptoms persisted despite treatment with mesalamine therapy until cornstarch was discontinued after 8 years of therapy. At 25 years of age, a colonoscopy was performed to evaluate recurrent bloody diarrhea. Visual inspection was normal, but histology was significant for mild and nonspecific
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
pancolitis. At that time, gastrointestinal feeds were reinitiated. All complaints resolved except intermittent episodes of brief rectal bleeding which is attributed to rectal prolapse.
Patient 3 The patient was diagnosed with GSD Ia at 3 months of age. Treatment consisted of continuous nasogastric feeds until transitioning to cornstarch at 42 months of age. At 14 years of age, a CT scan was performed secondary to acute onset abdominal pain. Findings raised concern for appendicitis and laparoscopy was performed. Inflammation of the terminal ileum was noted and then resected. The diagnosis of Crohn disease (CD) was made on histology of the specimen. The post-operative therapeutic regimen consisted of multiple ASAs. Due to a history of severe exacerbations, mercaptopurine (6-MP) and infliximab were added to her regimen. She has since transitioned to chronic therapy with 6-MP and mesalamine. While symptoms have improved, the patient continues to have episodes of abdominal pain and diarrhea approximately once every month.
Patient 4 The patient was diagnosed with GSD Ia at 5 months of age after presenting with failure to thrive, hepatomegaly and developmental delay. Treatment was overnight nasogastric feeds until the transition to cornstarch at 15 years of age. At 42 years old, the patient developed recurrent abdominal pain and diarrhea. An abdominal CT was suggestive of diffuse colitis. Two colonoscopies were performed when the patient was 45 years of age and showed mild active colitis at the terminal ileal valve, ascending and descending colon. A serologic screen for IBD was performed and consistent with CD. Therapy has consisted of multiple ASAs and anti-
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
motility medications. The patient had improved consistency of stools and fewer complaints of abdominal pain.
Patient 5 At 7 months of age, the patient was diagnosed with GSD Ia. Treatment was with continuous nasogastric feeds until 3 years of age. By 9 years of age, cornstarch was the only therapy. At the age of 18, an esophagogastroduodenoscopy (EGD) and colonoscopy were performed to evaluate complaints of abdominal pain, hematochezia and diarrhea. Histology was significant for chronic inflammation. The patient was diagnosed with UC. Treatment was escalated from an ASA to an immune modulator due to continued symptoms.
Discussion: The management of GSD has markedly improved over the past 40 years. Survival was rare prior to the 1970’s and most patients are now doing well into adulthood (6). With aging, long-term complications are appreciated, including the development of hepatic adenomas, hepatocellular carcinomas and hepcidin-induced anemia (6). IBD may be a new complication of the adult population with GSD Ia. Unlike most other complications, however, it appears to be unrelated to metabolic control since all of the afflicted patients had outstanding metabolic control at the time of diagnosis.
While an association between GSD Ib and IBD is well recognized, there are few reports focusing on the presence of diarrhea in GSD Ia, and none has linked this symptom to IBD. In this report, we presented five patients with enzymatically confirmed GSD Ia and endoscopically proven IBD
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
(two with CD and three with UC). The clinical and biochemical characteristics are presented (Tables 1 and 2). An additional four adult patients in our population are suspected to have IBD based on symptoms, inflammatory markers and serologic testing, but they were not included since histologic evidence is unavailable. The prevalence of symptomatic IBD in adults with GSD Ia followed at the University of Florida GSD program is 8.3% in contrast to the prevalence rate of IBD in adults in the United States which is reported to be 908 per 100,000 persons, or 0.9% (7).
In contrast to IBD found in the GSD Ib population, the patients with GSD Ia are developing this complication as adults. Colonic disease is also more common in GSD Ia while IBD in GSD Ib is almost exclusively limited to the small intestine (8). The IBD in GSD Ia also appears to be different from the general population since most go into remission with only ASA treatment. We suspect that IBD in GSD I may be caused by chronic uncooked cornstarch therapy, which could be altering the microbiota of the gastrointestinal tract, but further studies are needed to clarify the pathogenesis of this newly recognized complication.
At this time, we do not yet recommend screening procedures for IBD to be performed in the GSD Ia population in the absence of symptoms until further research can help clarify the cause of IBD development. If the patient starts to experience gastrointestinal abnormalities, then a serological panel or endoscopic procedure may be warranted in the case of persistent symptoms.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Conclusions: With improved survival of GSD patients, new co-morbidities are being recognized. The discovery of IBD in both subtypes of GSD I may provide valuable clues for understanding the development of IBD beyond this population. In general, there is no consensus regarding the pathophysiology of IBD. A complex interplay between genetic predisposition, impaired innate immunity, dysbiosis and environmental factors has been proposed. Future studies are warranted, and physicians should be aware of the possible association with GSD Ia.
Acknowledgements: This research was supported by philanthropic support provided by the following funds managed through the University Of Florida Office Of Development: Scott Miller GSD Program Fund and the GSD Dream Fund. Support for this project was also provided in part by the National Institutes of Health and National Center for Research Resources CTSA grants 1UL1RR029890 (University of Florida). The authors appreciate critical reading of an earlier version of the manuscript by Frank Hoentjen, MD, PhD (Radboud University Medical Center, Nijmegen, The Netherlands) and John E. Simmons, PhD (Trinity College, CT).
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
References: 1. Chen Y-T, Burchell A. Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease, 8th edition. New York: McGraw-Hill; 2001.
2. Lei KJ, Shelly LL, Lin B, et al. Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c.. J Clin Invest 1995;95(1):234-40.
3. Narisawa K, Igarashi Y, Otomo H, et al. A new variant of glycogen storage disease type I probably due to a defect in the glucose-6-phosphate transport system. Biochem Biophys Res Commun 1978;83(4): 1360-4.
4. Visser G, Rake JP, Fernandes J, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I. J Pediatr 2000;137:187-91.
5. Visser G, Rake JP, Kokke FT, et al. Intestinal function in glycogen storage disease type I. J Inherit Metab Dis 2002;25(4):261-7.
6. Weinstein DA, Wolfsdorf JI. Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease. Eur J Pediatr 2002;161 Suppl 1:S35-9.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
7. Nguyen GC, Chong CA, Chong RY. National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States. J Crohns Colitis 2014;8(4):288-95.
8. Davis MK, Valentine JF, Weinstein DA, Polyak S. Antibodies to CBir1 are associated with glycogen storage disease type Ib. J Pediatr Gastroenterol Nutr 2010;51(1):14-8.
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
Table 1. Clinical characteristics of patients at time of IBD diagnosis Patient 1 2 Sex F M
3 F
4 M
5 M
Age of diagnosis of GSD Ia (months) Mutation Adenomas Triglycerides (mg/dL) Uric Acid (mg/dL) Proteinuria (g/L)
3 R83C/R83C Yes 311 4 None
5 R83C/Q347X Yes 336 8 None
7 R83C/R83C None 124 4 None
7 W63X/V338F Yes 88 4 None
9 175delGG/866delA None 90 4 0.2
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Table 2. IBD characteristics and history of patients Patient 1 2
3
4
5
Age of diagnosis of IBD (years)
Symptoms
27
24
11
42
18
Hematochezia
Abdominal cramping and diarrhea
Abdominal pain and diarrhea
Abdominal pain and diarrhea
Abdominal pain, diarrhea and hematochezia
Resected tissue and colonoscopy
Colonoscopy
Colonoscopy
Ascending and transverse colon Crohn Disease 7 N/A
Pancolonic Ulcerative Colitis 58 N/A
Mesalamine
Mesalamine then infliximab
Endoscopy
Colonoscopy
Colonoscopy
Location of disease Prometheus Panel ESR at diagnosis (mm/hr) Calprotectin (mg/kg)
Pancolonic None N/A 305
Pancolonic None N/A N/A
Treatment
Mesalamine
Mesalamine
Ileal None 81 N/A Mesalamine then mercaptopurine, infliximab and mesalamine
Copyright © ESPGHAN and NASPGHAN. All rights reserved.
