Pseudoxanthoma elasticum: a cohort study and design of a registry.

Pseudoxanthoma Elasticum (PXE) is a rare, but severe genetic disease affecting
elastic fibres in the skin, vasculature and eyes. Patients suffer from vascular
morbidity and visual impairment at a relatively young age. Up to now, no
preventative treatment exists and little is known on the prognosis of an
individual patient. New insights into this disease, e.g. the course of disease,
associations between different clinical parameters and possible future
treatments, are needed. The aim of this study is to make a registry, where
clinical data is collected for research. To improve international collaboration
for this rare disease we want add an international questionnaire to this
registration.

Recently, low levels of the calcification inhibitor inorganic pyrophosphate
(PPi) were shown to be present in PXE patients and PPi and ENPP1 acitvity (the
enzym that forms PPi) levels might therefore be predictive for disease onset
and progression and level may explain the large variation in severity of the
disease. To get more insights into the pathophysiology of PXE a second aim of
this study is to measure PPi and ENPP1 activity in patients included in the
PXE registry and link this to clinical parameters. Furthermore, there is a need
to quantify ophthalmological disease in an earlier stage than the final visual
loss, which is a subjective measure. Up to now, it is not possible to measure
the severity of retinal calcification disease. We have made progress in
quantifying progression of retinal disease using indocyanine green angiograms
(ICGA) and hypothesize that these can be used to monitor ocular disease. Thus,
a third aim of this study is to perform ICGA in patients with PXE and to
measure progression of retinal calcification.
Lastly, in some patients there is acute vision loss, one hypothesis is that
this is cause by an auto-immune phenomenon. Therefore we want to analyse the
blood of PXE patients for anti-retinal antibodies and cytokines.

To collect data in order to create a registry that can be used for research in
PXE, partly with an international questionnaire, and to measure PPi, ENPP1
activity, anti-retinal antibodies and cytokines, and retinal calcification in
all patients included in the PXE national registry and link this to other
clinical and ophthalmological parameters.

Longitudinal observational cohort study

The burden for patients to participate in this study is minimal. A total of 27
ml extra blood will be collected as much as possible along with blood
collection for routine medical care. Furthermore, patients will receive one
injection each visit every two years with ICG which is also used in routine
ophthalmological care for decades. This will take minimal extra time and has
minimal risks. Participation or refusal to participate in the study will
neither have consequences for their treatment.