Outcomes of long term treatments of type I hereditary angioedema in a Turkish family.

BACKGROUND: Hereditary angioedema is a rare autosomal dominantly inherited immunodeficiency disorder characterized by potentially life-threatening angioedema attacks. OBJECTIVE: We aimed to investigate the clinical and genetic features of a family with angioedema attacks. METHODS: The medical history, clinical features and C1-INH gene mutation of a Turkish family were investigated and outcomes of long-term treatments were described. RESULTS: Five members had experienced recurrent swellings on the face and extremities triggered by trauma. They were all misdiagnosed as familial Mediterranean fever (FMF) depending on frequent abdominal pain and were on colchicine therapy for a long time. They had low C4 and C1-INH protein concentrations and functions. A mutation (c.1247T>A) in C1-INH gene was detected. They were diagnosed as having hereditary angioedema with C1-INH deficiency (C1-INH hereditary angioedema) for the first time. Three of them benefited from danazol treatment without any significant adverse events and one received weekly C1 esterase replacement treatment instead of danazol since she had a medical history of thromboembolic stroke. STUDY LIMITATIONS: Small sample size of participants. CONCLUSION: Patients with C1-INH hereditary angioedema may be misdiagnosed as having familial Mediterranean fever in regions where the disorder is endemic. Medical history, suspicion of hereditary angioedema and laboratory evaluations of patients and their family members lead the correct diagnoses of hereditary angioedema. Danazol and C1 replacement treatments provide significant reduction in hereditary angioedema attacks.

Outcomes of long term treatments of type I hereditary angioedema in a Turkish family

Abstract: Background: Hereditary angioedema is a rare autosomal dominantly inherited immunodeficiency disorder characterized by potentially life-threatening angioedema attacks. Objective: We aimed to investigate the clinical and genetic features of a family with angioedema attacks. Methods: The medical history, clinical features and C1-INH gene mutation of a Turkish family were investigated and outcomes of long-term treatments were described. Results: Five members had experienced recurrent swellings on the face and extremities triggered by trauma. They were all misdiagnosed as familial Mediterranean fever (FMF) depending on frequent abdominal pain and were on colchicine therapy for a long time. They had low C4 and C1-INH protein concentrations and functions. A mutation (c.1247T>A) in C1-INH gene was detected. They were diagnosed as having hereditary angioedema with C1-INH deficiency (C1-INH hereditary angioedema) for the first time. Three of them benefited from danazol treatment without any significant adverse events and one received weekly C1 esterase replacement treatment instead of danazol since she had a medical history of thromboembolic stroke. Study limitations: Small sample size of participants. Conclusion: Patients with C1-INH hereditary angioedema may be misdiagnosed as having familial Mediterranean fever in regions where the disorder is endemic. Medical history, suspicion of hereditary angioedema and laboratory evaluations of patients and their family members lead the correct diagnoses of hereditary angioedema. Danazol and C1 replacement treatments provide significant reduction in hereditary angioedema attacks.

An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics".

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.

Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics).

This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.

The Turkish Hereditary Angioedema Pilot Study (TURHAPS): the first Turkish series of hereditary angioedema.

BACKGROUND: No published data presently exist concerning hereditary angioedema (HAE) in Turkey. The aim of the study was to initiate a preliminary multicentric evaluation about HAE and to determine the genetic properties of Turkish patients. METHODS: Based on records drawn from four medical centers we identified a total of 70 subjects, belonging to 60 unrelated families, fulfilling clinical and laboratory criteria for diagnosis of HAE with C1 inhibitor deficiency. Ten type I patients, and their first-degree relatives, underwent genetic analysis for HAE. RESULTS: The majority of patients were female (60%), the mean age was 37.7 ± 14.1 years. The mean age at the time of first angioedema symptom was 12.5 ± 9.2 years. Mean time lag between first symptom and diagnosis was 26 ± 14.4 years. All but 3 subjects had HAE type I. Family history of angioedema was present in 75.7% of the cases. Cutaneous swelling was reported by 87.1% of the patients, facial edema by 65%, abdominal symptoms by 74.3% and approximately one half (55.7%) had experienced one or more laryngeal attack. Genetic analysis of 10 families demonstrated that 5 carried a mutation that had never been previously described. CONCLUSION: We found that the clinical features of Turkish HAE patients were consistent with previously described patterns of this rare disease. The most noteworthy feature identified in the study was a significantly long duration between the first symptom appearance and final diagnosis. Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease.

Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients.

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction-based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases.