All Articles

Hermann Gram*

Novartis Institutes of BioMedical Research, Forum 1, CH-4002 Basel, Switzerland

Inmaculada Martinez-Saguer^1* and Henriette Farkas²

¹Hemophilia Center Rhine Main, Germany
²Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Hungary

Sally Ann Lynch^1,2* & Jillian P Casey²

¹National Rare Disease Office, Mater Hospital Dublin 7, Ireland
²UCD Academic Centre of Rare Disease, School of Medicine and Medical Sciences, Belfield, Dublin 4, Ireland

 European Reference Networks are being established across the EU with the aim of improving the care of patients with rare diseases. Recognising that experts are rare, ERNs are tasked with the aim of encouraging collaboration of experts across individual member states. Membership of an ERN is dependent on fulfilling criteria to allow one to be described as a centre of expertise. ERNs will produce guidelines through consensus and the development of EU wide registries should help to facilitate clinical trials. However, the ERN entry requirements are such that some member states will struggle to fulfil the criteria. Investment in trained staff for rare diseases has been poor in some countries risking the possibility that ERN membership may be restricted to a limited number of member states.

Hugh James Freeman*

Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, Canada

 A rarely diagnosed clinical and pathological disorder was historically characterized by multiple benign small intestinal ulcers, involving the mucosa and, occasionally, the submucosa of the small intestine, and histopathologically by non-specific inflammatory changes without granulomas. These early reports also noted that recurrent episodes of abdominal pain often developed due to obstructive events, sometimes associated with localized stricture formation. This usually responded to steroid treatment, intestinal resection, or both. Recent advances owing largely to emerging imaging methods have provided added criteria for separation of this entity from other disorders, including Crohn’s disease and medication-related small bowel ulceration. Most important, recent long-term follow-up studies have suggested a potential for confusion with other functional or motility-based clinical disorders and emphasize the likelihood of a much more benign clinical course.

Michel Lebel*

Centre de recherche du CHU de Québec, Faculty of Medicine, Université Laval, Quebec City Quebec, Canada

 Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a pro-oxidant/pro-inflammatory status, genomic instability, and by the premature onset of several age-associated diseases. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication, repair, and transcription. This review focuses on the beneficial impact of vitamin C treatment in mutant mouse and worm models of WS with an emphasis on serum metabolomic and cytokinome profiles in Wrn mutant mice. Vitamin C normalizes the health and life span of these mutant animals. More importantly, our recent results indicate that it will be possible to follow the beneficial impact of vitamin C at a systemic level by monitoring specific serum metabolites and inflammatory cytokines in a longitudinal study involving WS patients.

Paula G. Franco^1,2, Ana M. Adamo^1,2, Patricia Mathieu^1,2, María J. Pérez^1,2, Patricia C. Setton-Avruj^1,2 and Lucas Silvestroff^1,2*

¹Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Química Biológica Patológica. Buenos Aires, Argentina
²Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica

Biológicas (IQUIFIB) Profesor Alejandro C. Paladini, Facultad de Farmacia y Bioquímica, Argentina

 Lysosomal Storage Disorders (LSD) are rare diseases that as a whole have a combined incidence ranging from 1:1500 to 1:7000 live births. One of such diseases is Mucopolysaccharidosis VI (MPS VI), or Maroteaux Lamy Syndrome. MPS VI patients undergo devastating and irreversible skeletal alterations and multisystemic failure as from early childhood due to reduced Arylsulfatse B (ARSB) enzyme activity.

Reaching a final diagnosis is not always a short cut path, but rather a years-long battle against uncertainty and unnecessary medical interventions. Our aim is to contribute from the bench table with different approaches that could serve as alternatives to pre-existing assays for screening and diagnosing MPS VI and other LSD.

The present work is based on our research article authored by Franco et al.1 where we studied the effect of blood-derived hemoglobin, and other blood components, on the fluorescence of 4-Methylumbelliferone when measuring ARSB enzyme activity from dried blood spot (DBS) samples.

Our experience indicates that to date there are plenty of different approaches for measuring ARSB enzyme activity, although the sample type required or the assay in itself often make them more adaptable for either high throughput screening or small scale diagnostics.

As a whole, the fluorometric determinations seem to be the most accessible to low budget laboratories with equally valuable performances as a sophisticated mass spectrometry analysis for this disease. Furthermore, the DBS serves as an attractive sample type for screening the disease in large populations.

Tu-Anh Tran^1*, Anne Filleron¹, Mathieu Simonin² and Pierre Corbeau³

¹Department of Pediatrics, Nîmes University Hospital, INSERM U 1183, Montpellier-Nîmes University, Nîmes, France
²Institut Gustave Roussy, Department of Pediatric Oncology, 114 Rue Paul Vaillant, 94800 Villejuif, France
³Department of Immunology, Nîmes university hospital, Montpellier-Nîmes university, Nîmes, France

 Systemic capillary leak syndrome (SCLS), is a rare condition characterized by a recurrent stereotypical triad: hypovolemic shock, generalized edema, paradoxical hemoconcentration and hypoalbuminemia. It is caused by massive fluid extravasation into the interstitial space. Mortality may result from hemodynamic failure in the acute phase or cardiac failure due to reflex circulatory overload in the sub-acute phase. To date, twenty-one pediatric cases were reported in the literature. Sex ratio (M/F) was 0.32 with a median age at disease onset of 5.7 years and at diagnosis of 6 years. The disease was recurrent in 81% of patients with a median of three attacks. Severe complications were possible involving central nervous system (n=2) or rhabdomyolysis, with a compartment syndrome needing fasciotomy (n=5). The median time to clinical recovery was five days. Although the clinical manifestations of pediatric and adult SCLS were similar; in the opposite of adult SCLS, none of the children showed evidence of monoclonal gammopathy and three pediatric cases had a family history of SCLS. Seventy five percent of the patients were treated with prophylactic treatment (mainly immunoglobulins, theophylline plus verapamil). Several inflammatory cytokines were suspected to be involved in the pathophysiology of SCLS, especially interleukin-17 and tumor necrosis factor -alpha.