Italia Meeting Report

Report of the Annual Meeting of the Association PXE-Italia


PXE Italia Meeting Brochure On the 16th of May 2009, at the University of Modena and Reggio Emilia, the Association PXE-Italia organized its 9th annual meeting open to patients, relatives, friends, doctors and researchers. There were more than 100 people in attendance. The great majority already had contact with PXE-Italia, but there were also patients new to the organization. The meeting lasted the entire day. We had lunch together at the cafeteria of the University and that was a good occasion to meet each other, to exchange experiences, and to discuss freely with doctors.

The goal of the meeting was to inform patients and relatives of the latest discoveries, to give them practical information on managing a heart-healthy diet and lifestyle, on how skin changes can be corrected with plastic surgery, and on new approaches to eye therapies.

The first talk was given by Deanna Guerra, PhD, who has been working with us for more than 20 years. She is an expert in the structural and ultrastructural analysis of biopsies, and now is in charge of the relationships with patients, sample collection and coordination of molecular biology analyses. She described what our group has done in the last 15 years: collection of samples from more than 200 Italian PXE patients, creation of the Association PXE-Italia that numbers more than 350 members, and that our laboratory is considered the reference center in Italy for the identification of ABCC6 mutations and for the study of the pathogenesis of elastic fiber calcification. 
(Photo: Deanna Guerra, PhD)
Daniela Quaglino, PHD Daniela Quaglino, PhD, Professor of General Pathology at the University of Modena and Reggio Emilia, is an expert in cell biology, gene expression and proteomic analyses. She spoke next, and showed that PXE is a complex disorder caused by mutations in the ABCC6 gene, but that there is no direct relationship between mutations in the gene and clinical signs of the disorder. Instead, clinical manifestations are the consequence of a series of metabolic alterations, first in the liver and then in peripheral cells. These peripheral cells probably have impaired production of molecules that normally inhibit calcium precipitation in the extracellular space and within the elastic fibers. The final result is mineralization and rupture of elastic fibers with several effects on the structure/function of connective tissues, especially of those containing a great amount of elastin, such as mid-sized arteries and the Bruch´s membrane of the retina. She also illustrated the metabolic pathways involved in elastic fiber calcification and possible points where specific treatments may modify and correct metabolic changes responsible for the fiber calcification. 
(Photo: Daniela Quaglino, PhD)
PXE Italia Meeting Ivonne Ronchetti and Valeria Azzaroni, President, PXE Italia
PXE Italia Audience Ivonne Ronchetti and
Valeria Azzaroni, President, PXE Italia

A number of Italian PXE patients are young women with severe skin laxity, especially in the axillae and groin. A young plastic surgeon, Fulvio Panico, MD, University of Modena and Reggio Emilia, described the experience and the satisfactory results obtained by the Modena´s group of plastic surgeons in reducing the skin sagging in three PXE patients (axilla, groin and neck). 
(Photo: Fulvio Panico, MD)

Alberto Martignani, MD Alberto Martignani, MD, vascular specialist at the S. Orsola Hospital in Bologna, has a great deal of experience with PXE, as he has been caring for Italian patients for more than 10 years. He´s the favorite vascular specialist of the Association PXE-Italia. He explained the first signs of vessel changes and which organs are affected. He also explained his experience with PXE patients and analyzed his own and the literature´s data to try to describe a correlation between blood vessel and eye changes in patients and the age of onset and severity of overall clinical manifestations in PXE. The conclusion is that blood vessel alterations generally affect all organs, the eyes included. By contrast, there is no apparent correlation between age of onset of peripheral vascular disease and progression and severity of global clinical manifestations in PXE.
(Photo: Alberto Martignani, MD)
Milena Cavazutti, MD The neurologist Milena Cavazzuti, MD, University of Modena and Reggio Emilia, is chief of the Stroke Unit of the S. Agostino Hospital in Modena and expert in neurovascular complications. She started to collaborate with PXE-Italia about two years ago, by preparing a questionnaire that was sent to all patients by mail. The questionnaire is rather simple, is used also for other neurological disorders and contains questions sufficient to understand if patients have neurological vascular involvement. She received responses from more than 120 patients. She presented very preliminary data suggesting that blood vessels in the brain may be affected in PXE. She described how to recognize preliminary signs of neurological involvement and what to do in such cases. 
(Photo: Milena Cavazzuti, MD)
Andrea Sodi, MD Andrea Sodi, MD, retinologist at the Careggi Hospital in Florence, University of Florence, has been collaborating with PXE-Italia since 2000. He examines and plans the follow up for a great number of PXE Italian patients. He has been studying for several years changes in blood vessels in Bruch´s membrane due to Age-Related Macular Degeneration, and has a great deal of experience in treating patients with injections of antiangiogenetic drugs. He explained in detail how PXE causes retinal hemorrhages in PXE, which changes in visual acuity are caused by PXE and which are due to other causes, and what can be done in various circumstances. His talk was very practical and several patients had retinal images, OCT (Optical Coherence Tomography) and fluoroangiographies to show him. During lunch Dr. Sodi could not be seen because of the wall of patients surrounding him! 
(Photo: Andrea Sodi, MD)
The last speaker was Dealba Gheduzzi, who received her degree in Biology by completing an experimental thesis on PXE, and stayed with us for a number of years working on PXE. She established the protocol for the identification of mutations of the ABCC6 gene, and started investigation on the expression of splice variants of ABCC6 by human skin fibroblasts. But then, for family reasons and her need for a more stable income in the future (her funding was only sporadic, mostly from PXE International), she decided to leave the University and to specialize in nutrition. She took specific courses and gained experience and now she can realistically approach the problem of what kind of nutrients, minerals, and vitamins can be helpful in PXE. Given her experience in biology, she can evaluate suggested nutritional interventions in the literature and which experimental and epidemiological data might validate these suggestions. She is rather skeptical that the addition of a single nutrient may help. Instead, she suggests a balanced diet, rich in vegetables and limited portions of meat, containing natural antioxidants, natural vitamins and minerals. She illustrated how vitamins, minerals and antioxidants, even in combination, are not properly absorbed if given in pills, but are much more active when administered through natural fresh vegetables, fruits and fish, where these compounds are associated with a nanomolar concentration of yet to be understood molecules that facilitate their absorption, transport and metabolism. While waiting for a specific and experimentally validated therapy, she suggests being careful with the addition of nutrients to a normal healthy diet. In agreement with Dr. Martignani, she also suggested moderate regular exercise to maintain and stimulate the peripheral circulation. 
(Photo: Dealba Gheduzzi)
PXE Italia Meeting
PXE Italia Meeting

Luigi Vanni, Vice President, PXE Italia


Sandra The audience was then invited to ask questions of the speakers. Two main issues were raised. The first, specific to Italy but having a corollary in other countries, was about convincing a number of regional health service administrators to consider PXE a genetic disorder that requires periodic exams and expensive eye treatments, but without any reimbursement. Although Italian law recognizes PXE as a genetic disorder that should be treated free of charge, this is not followed by all regional administrations. The second point discussed was how to find funding for research. A number of ideas were discussed and some were approved. Alessandra Giacomazzi, a journalist, suggested building an internet forum for exchanging ideas and suggestions. The idea will be explored.
(Photo: Allesandra Giacomazzi)
At the end, I tried to summarize the day. I presented my warmest thanks to the speakers and to participants. I announced my retirement in 2010, reminding everyone that the group composed of Daniela Quaglino, Deanna Guerra, Federica Boraldi and Giulia Annovi will continue to work on PXE and for the Italian patients. Finally, I confirmed my special thanks to PXE International, to Sharon and Pat Terry for their support and friendship during all these years.

Of course, I will not disappear, I hope, and I will continue to give my contributions. (Profile Ivonne Ronchetti)
(Photo: Ivonne Ronchetti)

Ivonne Ronchetti