Gastrointestinal Phenotype of Fabry Disease in a Patient with Pseudoobstruction Syndrome

Buda, Piotr; Wieteska-Klimczak, Anna; Książyk, Janusz; Gietka, Piotr; Smorczewska-Kiljan, Anna; Pronicki, Maciej; Czartoryska, Barbara; Tylki‐Szymańska, Anna

doi:10.1007/8904_2011_63

Cited by 13 publications

(14 citation statements)

References 13 publications

(14 reference statements)

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“…These were mostly mild to moderate in severity, although 4 (13%) patients experienced severe abdominal pain. One of these patients had been the subject of a separate, independent report, due to the unusually severe GI manifestations [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Wijburg

Bénichou²,

Bichet

et al. 2015

PLoS ONE

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Trial DesignThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial RegistrationClinicalTrials.gov NCT00701415

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Section: Resultsmentioning

confidence: 99%

Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Wijburg

Bénichou²,

Bichet

et al. 2015

PLoS ONE

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“…Although heterozygous females were previously considered carriers, almost half of females may experience gastrointestinal symptoms and some of those symptoms, such as constipation, are reported almost twice as often by female patients as by male patients . In some cases the gastrointestinal symptoms can dominate the clinical picture, presenting as a so‐called ‘gastrointestinal phenotype’ of Fabry disease . It is well known that gastrointestinal involvement can be the first and only manifestation of Fabry disease for years.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal involvement in Fabry disease. So important, yet often neglected

Politei

Thurberg²,

Wallace

et al. 2015

Clinical Genetics

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Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms-abdominal pain, nausea, diarrhea and diverticular disease--are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.

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“…GI symptoms are some of the earliest and most commonly reported symptoms in Fabry disease, and include abdominal pain, bloating, diarrhoea, constipation, nausea, and vomiting [101,140,143,144]. One study found that GI symptoms occurred in approximately 60% of children and in 50% of adults, and had a serious negative effect on QoL [143].…”

Section: Gastrointestinal Dysfunctionmentioning

confidence: 99%

European expert consensus statement on therapeutic goals in Fabry disease

Wanner

Arad

Baron

et al. 2018

Molecular Genetics and Metabolism

144

149

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Gastrointestinal Phenotype of Fabry Disease in a Patient with Pseudoobstruction Syndrome

Cited by 13 publications

References 13 publications

Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

Gastrointestinal involvement in Fabry disease. So important, yet often neglected

European expert consensus statement on therapeutic goals in Fabry disease

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