The objectives аre to evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet’s disease (BD). Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet’s Syndrome Activity Score (BSAS), Behçet’s Disease Current Activity Form (BDCAF) score, Behçet’s Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P-value <0.05 was considered statistically significant. Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy. For more information click here.
Publications
Primary spontaneous pneumothorax (PSP) is not an uncommon disease, especially in patients with risk factors such as male gender, history of smoking, and low body mass index (BMI). Amyotrophic lateral sclerosis (ALS) is a rare disease caused by neurodegeneration of the motor neurons that share risk factors with PSP. The aim of this study was to determine the prevalence of PSP in ALS and find the significant risk factors related to PSP. We retrospectively reviewed the data from 86 patients with clinically probable or definite ALS from three different centers. Clinical characteristics, including age, sex, subtype, disease duration, body mass index, history of smoking, tracheostomy state, and ventilator use, were obtained. The ALS Functional Rating Scale-Revised Form (ALSFRS-R) total score and subscores were also retrieved from the medical records. In the results, six of the 86 patients (7%) had PSP. There were no statistically significant differences among the clinical characteristics and the ALSFRS-R scores between the patients with and without PSP, except for BMI and smoking (p < 0.022 and p < 0.019, respectively). A multivariate logistic regression analysis of smoking and BMI showed an odds ratio of 19.25. In conclusion, the existence of PSP in ALS may be under-recognized. Further well-designed, large studies are needed to elucidate the prevalence and pathophysiology of pneumothorax in ALS. For more information click here.
Multiple Endocrine Neoplasia type 1 (MEN1) has been causing problems for clinicians since it was described in 1954 by Wermer. Not only its rarity, but also variable clinical manifestations and no genotype-phenotype correlation make it hard to establish evidence-based guidelines for management of this syndrome. Nationwide registers and population-based researches are the best means to improve knowledge about this rare disease. By now, there was no example of such research in the Polish population of MEN1 patients. We performed a retrospective analysis of clinical and genetic data of patients diagnosed with MEN1 syndrome and followed-up in two polish referral centers in years 1994-2018. Polish population of patients with MEN1 is different than previously described European and Asian populations primarily in prevalence of functional NETs. Frameshift mutation with STOP codon of MEN1 gene increase significantly risk of PA. Further studies, with a larger cohort of patients, are needed to fully describe the Polish population and improve diagnosis and management of the syndrome. For more information click here.
The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60% of UCDs patients, and comparison between individual diseases showed a significant higher frequency in ASLD and in HHH syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients’ cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs. For more information click here.
Angiodysplastic (AD) lesion is the most common cause of recurrent gastrointestinal (GI) bleeding in inherited Von Willebrand disease (VWD) patients lacking high-molecular-weight multimers. Defect or dysfunction of von Willebrand factor (VWF) may lead to enhanced endothelial cell proliferation followed by the development of neoangiogenesis and vascular malformation, which result in severe bleeding. Recurrent bleeding causing by GI AD is a challenging complication of VWD. The management of VWD could be difficult due to frequent recurrence and severity of bleeding episodes. The primary aim of management is not only to stop but also to prevent bleeding. We present two patients of type 3 VWD associated with AD and severe GI bleeding, which were successfully treated by endoscopic coagulation and prophylactic therapy with different regimens of plasma-derived VWF/factor VIII (pdVWF/FVIII) concentrate to maintain a trough level in the patient unresponsive to standard treatment. For more information click here.
Тази година 10-та Юбилейна национална конференция за редки болести и лекарства сираци ще се проведе под официалния патронаж на Министерството на здравеопазването.
В писмото си министъра на здравеопазването Кирил Ананиев изказва своето уважение към дейностите на Информационния център за редки болести и лекарства сираци. Той посочва още същественото значение на информираността при лечението на хората с редки болести и техните близки, с което се подобрява качеството им на живот. Министъра споделя, че със съвместни усилия могат да се подобрят условията за лечение на всички пациенти, включително и на хората с редки болести, чрез предоставяне на достъпна и достоверна информация за тези заболявания, както и за възможностите за лечение и рехабилитация.
Конференцията ще се проведе на 13-15 септември 2019 г. в Конгресен център на Международен панаир Пловдив. Основна тема на събитието ще бъдат новостите и актуалните тенденции в диагностиката, лечението и проследяването на редките болести, развитието на европейските референти мрежи и достъпа до иновации в областта на редки болести. Подробна информация за събитието, програмата и възможност за регистрация може да получите на официалната страница на събитието.
The Nobel Prize winner of the Medicine Award in 1993, Prof. Philip Sharp will visit “Alexandrovska” University Hospital. Prof.Sharp will give a lecture on “RNA interference and its medical applications” on 12th July 2019 at 11.00h in the “Maxima” auditorium of University Hospital “St. Ekaterina”, Sofia. The audience will include academic researchers, neurologists, specialistis in medical genetics, biology, chemistry and biochemistry. Representatives of patients’ organizations of people with rare diseases, journalists, medical professionals and others are also invited. There will be a discussion after the end of the lecture on which Prof. Sharp will answer questions from the audience. The press release of the event can be downloaded from this link.
The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dubé Syndrome
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disorder characterized by inactivation of the gene Folliculin (FLCN), pulmonary cysts with recurrent spontaneous pneumothorax, dermatological lesions, and an increased risk of developing renal malignancies. We aimed to investigate the real prevalence of BHDS and its prevalence among patients with a familial history of pneumothorax. From July 2014 to December 2016, we consecutively studied all patients with spontaneous pneumothorax and a positive family history for the same condition referring to our Institution. The suspicious cases underwent genetic analysis of the BHDS-causative gene FLCN. FLCN-positive cases were further evaluated with routine blood tests, chest radiography, chest CT, abdominal MRI, and dermatological evaluation. Although BHDS is considered a rare disease, BHDS underlies spontaneous pneumothorax more often than usually believed, especially whenever a family history of pneumothorax is present. Diagnosis of BHDS is essential to start monitoring patients for the risk of developing renal malignancies. For more information click here.
Uncommon characteristics in genetically unsolved retinitis pigmentosa (RP) patients may indicate an incorrect clinical diagnosis or as yet unknown genetic causes resulting in specific retinal phenotypes. The diagnostic yield of targeted next-generation sequencing may be increased by a reasonable preselection of RP-patients. The participants in the study are one-hundred and twelve consecutive RP-patients who underwent extensive molecular genetic analysis. The methods, used in the study are characterization of patients based on multimodal imaging and medical history. Compared to genetically solved patients, genetically unsolved patients more frequently had an age of disease-onset above 30 years, showed atypical fundus features and indicators for phenocopies (eg, autoimmune diseases). Evidence for a particular inheritance pattern was less common. The diagnostic yield was 84% in patients with first symptoms below 30 years-of-age, compared to 69% in the overall cohort. The other selection criteria alone or in combination resulted in limited further increase of the diagnostic yield (up to 89%) while excluding considerably more patients (up to 56%) from genetic testing. The medical history and retinal phenotype differ between genetically solved and a subgroup of unsolved RP-patients, which may reflect undetected genotypes or retinal conditions mimicking RP. Patient stratification may inform on the individual likelihood of identifying disease-causing mutations and may impact patient counselling. For more information click here.
We present five Danish individuals with Hajdu-Cheney syndrome (HJCYS) (OMIM #102500), a rare multisystem skeletal disorder with distinctive facies, generalised osteoporosis and progressive focal bone destruction. In four cases positive genetic screening of exon 34 of NOTCH2 supported the clinical diagnosis; in one of these cases, mosaicism was demonstrated, which, to our knowledge, has not previously been reported. In one case no genetic testing was performed since the phenotype was definite, and the diagnosis in the mother was genetically confirmed. The age of the patients differs widely from ten to 57 years, allowing a natural history description of the phenotype associated with this ultra-rare condition. The evolution of the condition is most apparent in the incremental bone loss leading to osteoporosis and the acro-osteolysis, both of which contribute significantly to disease burden. For more information click here.