Review of gastrointestinal symptoms for Fabry disease.
Review of impact from Fabry disease.
Review of differential diagnosis for Fabry disease.
Explanation of GI study for Fabry disease.
2. Disclosure
• I am involved in a Genzyme supported ISS examining GI dysfunction
in Fabry disease
• I have no other financial disclosures
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3. Topics
• What do we know about gastrointestinal
symptoms?
– Type and cause
• What are treatment options?
– ERT
– GI medications
• Fabry study on gastrointestinal symptoms
at Massachusetts General Hospital
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4. Prominent Symptoms
• Abdominal Pain
– Most common symptom
– Cramping, mid-abdominal
– Worsened with food intake or stress
• Increased metabolic demand
• Diarrhea
– Increased urgency and frequency
– Some exclusively intake-associated
• Fatty foods, lactose
– No blood or mucous
• Constipation
– Almost twice as common in females1
1. Buda et al, Curr Pharm Des, 20134
5. Other symptoms
• Nausea, vomiting, early satiety
– Slow in stomach emptying
• BMI
– Conflicting finding, some lower Body-Mass Index
(BMI) vs. normal
• Severe and rare:
– Perforation
– Colostomy
– Fistulas
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6. Quality of Life
• Gastrointestinal symptoms severe impact on quality of life
• Adult patients with gastrointestinal symptoms had lower
quality of life score than patients without gastrointestinal
symptoms
• Pediatric Fabry patients have lower quality of life scores as
compared to age-matched children in the general US
population
• Anecdotally
– School and work absence
– Social isolation due to discomfort and embarrassment
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8. Differential Diagnosis
• Irritable Bowel Syndrome-Diarrhea
• Gastroesophageal reflux
• Inflammatory Bowel Disease
• Celiac Disease
• Scleroderma
• Mitochondrial disease
• Dermatomyositis
• Appendicitis
• Other lysosomal and glycogen storage diseases
• Delay in diagnosis of up to 10 years as symptoms
nonspecific
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9. Treatment: Enzyme
Replacement Therapy
• Shown to reduce glycolipid accumulation in tissue
– Effective in stabilizing and sometimes reversing skin,
renal and cardiac disease1
– Variable effects on the GI symptoms
• Hoffman et al, 2007 studied 342 patients adult and
pediatric2
– Reduce overall prevalence gastrointestinal at 24 month
post initiation
– Improved quality of life (0.63 to 0.71)
– 2/3 patients continued to have gastrointestinal
symptoms
10. Evaluation & Management
Persistence of gastrointestinal symptoms even in
the setting of prolonged ERT
Role for more targeted therapeutic intervention
Fabry
Symptoms
Abdominal
Pain
Diarrhea Gastric
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11. Summary
• Gastrointestinal symptoms can be severe and lead to a
significant decrease in quality of life
• Little known about exact mechanism, but thought to be
due to similar mechanism of dysfunction seen in other
systems
– Suspected to be a motility disorder
• Enzyme replacement therapy can improve some
symptoms, however gastrointestinal symptoms continue
to be a significant source of problems among Fabry
patients.
• There is much that can and should be done in the
management of this aspect of the disease
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13. Goals & Objectives
• There is limited information about the underlying causes of
the gastrointestinal diseases in patients with Fabry
disease
– Muscle abnormalities
– Vessel Abnormalities
– Nerve Abnormalities
• Gastrointestinal symptoms frequently persist even when
being treated with enzyme replacement therapy.
• Much can be learned by examining the GI tract in order to
provide improved management and care for these types of
symptoms in Fabry disease
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14. Study Goals
• Dysmotility
– Examine how the GI tract moves
– Evaluate the types of abnormalities in the movement of the
gut, including changes in the muscles and the nerves, to
better understand the underlying GI dysfunction
• Histology
– Analysis of the tissue of the GI tract under a microscope to
study the cell changes
– Examine the cells to assess the amount of accumulation of
glycolipid in the GI tract
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15. Study Design
A. Validated Questionnaires
– GI symptoms
• Stool frequency
• Stool types
• Abdominal pain
• Depression/Anxiety
• Upper GI symptoms (nausea, vomit)
– Quality of life
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16. Study Design
• B. Motility
– SmartPill, 5 day assessment:
• Whole-gut transit
• pH
• Contractility
– Ingest SmartPill, receiver kept close
– Pass pill in stool and return receiver
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17. Study Design
• C. Histology
– Clinically warranted sigmoidoscopy (Diarrhea,
abdominal pain)
– Endoscopic mucosal resection taken during
sigmoidoscopy
• Tissue examined under microscope
– Light microscopy
– Electron microscopy
– Cellular changes (swelling, damage)
• Count amount of glycolipid accumulation
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18. Outcomes
• SmartPill
– Abnormalities of movement (slow or fast passage)
• Histology
– Cellular changes
– Glycolipid accumulation
• Psychosocial
– Depression/Anxiety
• Quality of life
– Quality of life scale
• Medical Care Use
– Doctor’s visits, ER visits
• GI Symptom Protocol
– Intention of creating a protocol to aid in evaluation of Fabry-related
gastrointestinal issues
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19. How to get involved?
• Do you meet criteria?
– SmartPill &Questionnaires
• Fabry disease
• GI symptoms, any severity
• 18-70 years old
• Do not have other GI diseases
– Biopsy/Sigmoidoscopy section:
• Meet criteria for above
• AND ERT naïve or < 6 months
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20. How to get involved?
• Study being conducted in Boston, MA
– Dr. Braden Kuo (GI)
– Dr. Claire Zar-Kessler (GI)
– Dr. Amel Kaara (Genetics)
• Patient needs to travel to Massachusetts General Hospital
– Typically 2 day study, stay overnight
– Travel and lodging for the night covered by study
– Compensation provided for participation in the study
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