Pseudoxanthoma Elasticum
Conditions
Keywords
PXE, calcification, Gla proteins, gut microbiota, vitamin K2, menaquinones, taxonomic meta-sequencing
Brief summary
This study aims to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K, and severity of clinical manifestations of Pseudoxanthoma Elasticum (PXE).
Detailed description
Vitamin K deficiency contributes to pathological calcification which underlies the clinical picture of pseudoxanthoma elasticum (PXE), an inherited autosomal recessive disease. A substantial proportion of vitamin K, namely the K2 form (menaquinones), is produced by gut microbiota. In healthy volunteers fecal levels of the major menaquinone producers, Escherichia coli and Bacteroides species, are approximately 5 and 9 log10 CFU/g dry weight respectively. There is however a lack of data on gut microbiota in PXE patients. The objective of our project is to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K and severity of clinical manifestations in PXE patients. This study will be performed as Research surrounding bio collection Clinical and biological exploration of PXE patients kept at the Center of Biological Resources of Angers University Hospital (bio collection n° DC 20116-14-67, authorization to transfer n° 2016-27-99). Fecal samples, plasma samples and clinical data will be collected from patients diagnosed with PXE who will be monitored at the Angers University Hospital Referral Center (France) in 2019-2020. Clinical severity of PXE will be assessed using modified Phenodex score. Gut microbiota will be analyzed using metagenomic sequencing. Plasma Vitamin K species and fecal excretion of menaquinones will be assessed using HPLC. Plasma dp-ucMGP (circulating biomarker of vitamin K status) and serum PIVKA-II (protein induced by vitamin K absence-II) will be assessed using immunoassay. Results will be compared to healthy age- and gender-matched controls from the pre-existing Biofortis database.
Interventions
DIAGNOSTIC_TESTFecal and blood samples
Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K
Sponsors
Maastricht University
Biofortis Mérieux NutriSciences
University Hospital, Angers
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with phenotypically and genetically (ABCC6) proven PXE * Aged over 18 years * Written consent obtained for Angers University Hospital (France) PXE bio-collection
Exclusion criteria
* Patients under the age of 18 * Patients unwilling to participate in the study, or unable to sign the bio-collection consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fecal samples for assessment of various forms of vitamin K | 15 min | Fecal Vitamin K species |
| Blood samples for assessment of various forms of vitamin K | 15 min | Plasma Vitamin K species |
| Blood samples for assessment of dp-ucMGP | 15 min | Plasma dp-ucMGP |
| Blood samples for assessment of PIVKA-II | 15 min | Serum PIVKA-II |
| Fecal samples for intestinal microbiota analysis | 15 min | Gut microbiota composition and relative abundance of species (via metagenomic sequencing) |
| Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes | 15 min | Modified Phenodex score: * Skin lesions severity: S0=No sign; S1= Papules/bumps; S2= Plaques of coalesced papules; S3= Lax and redundant skin * Number of affected skin sites: for Typical and Nontypical areas * Ophthalmological involvement: E0= No sign; E1= Peau d'orange ; E2= Angioid streaks; E3a=Medical history of bleeding and/or scarring; E3b= Unilateral or bilateral blindness * Gastrointestinal bleeding: G0= No sign; G1= Gastrointestinal bleeding as related to PXE * Vascular involvement: V0= No sign; V1= Weak or absent pulse or peripheral artery disease revealed by vascular imaging; V2= Intermittent claudication; V3= Medical history of vascular surgery or Stroke/TIA * Cardiac involvement: C0= No sign; C1= medical history of chest pain/angina/abnormal EKG or abnormal stress test with no symptom, or Mitral insufficiency; C2= Heart attack * Renal involvement: R0= No sign; R1a= asymptomatic nephrocalcinosis revealed by imaging; R1b= Nephrolithiasis |
Countries
France, Netherlands
Contacts
Primary ContactLudovic MARTIN, MD, PhD
Outcome results
None listed