Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

/pdf/guidelines-for-the-management-of-hemophilia-1x6t2d999b.pdf

Guidelines for the management of hemophilia.

A second gene for autosomal dominant polycystic kidney disease was identified by positional cloning. Nonsense mutations in this gene (PKD2) segregated with the disease in three PKD2 families. The predicted 968-amino acid sequence of the PKD2 gene product has six transmembrane spans with intracellular amino- and carboxyl-termini. The PKD2 protein has amino acid similarity with PKD1, the Caenorhabditis elegans homolog of PKD1, and the family of voltage-activated calcium (and sodium) channels, and it contains a potential calcium-binding domain.

http://science.sciencemag.org/content/sci/272/5266/1339.full.pdf

PKD2, a Gene for Polycystic Kidney Disease That Encodes an Integral Membrane Protein

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60601-1.pdf

Autosomal dominant polycystic kidney disease

In vivo gene replacement for the treatment of inherited disease is one of the most compelling concepts in modern medicine. Adeno-associated virus (AAV) vectors have been extensively used for this purpose and have shown therapeutic efficacy in a range of animal models. Successful translation to the clinic was initially slow, but long-term expression of donated genes at therapeutic levels has now been achieved in patients with inherited retinal disorders and haemophilia B. Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease.

Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease occurring in 1 in 200 to 1 in 1,000 individuals. ADPKD is characterized by cystic lesions in the kidneys and often by structural abnormalities in the gastrointestinal tract and cardiovascular system. The pathogenesis of the disorder appears to involve both cellular proliferation and altered extracellular matrix synthesis. Diagnosis can be established most readily by the sonographic demonstration of renal cysts or by gene linkage analysis. Renal manifestations of ADPKD include hypertension, infection, nephrolithiasis and malignancy. The prominent extrarenal manifestations include hepatic cysts, mitral valve prolapse and intracranial aneurysms. Although only 2% of nephrons appear to be involved in cyst formation, the renal function often slowly deteriorates. Presently, there is a 52% probability of an ADPKD subject’s being alive without renal replacement therapy at age 73. ADPKD patients with endstage renal disease respond to renal replacement therapy as well as other patient groups.

Autosomal dominant polycystic kidney disease.

Four cases of Kleeblattschadel demonstrated on prenatal ultrasound examinations are reported. Five additional cases from the literature are reviewed. Sonographic features include enlarged trilobed skull, hydrocephalus, polyhydramnios, and frequent association with thanatophoric dwarfism. The most common error in diagnosis was misinterpretation of this skull anomaly as encephalocele.

Kleeblattschadel anomaly: in utero sonographic appearance

Despite the vast number of published papers relating to the treatment of bleeding disorders there are relatively few controlled prospective studies in this ®eld. This means that many therapeutic decisions are made by reference to incomplete scienti®c data. It is clear that the management of bleeding disorders will continue to evolve, not only because of technological developments but also because of the accumulation of new treatment-related research. A 2-day meeting was held in London on January 15±16, 2001. The aim of the meeting was to discuss the current best practice and to identify areas where further research is required to make the most impact on the optimization of treatment regimes for individuals with bleeding disorders. The meeting was chaired by Louis Aledort, MD, and consisted of a small group of invited experts to discuss aspects of haemophilia care. This group presented and discussed data from existing and recent research in an attempt to identify areas of current consensus and areas that warrant future research. The meeting was sponsored by educational grants donated by a number of pharmaceutical companies, who were invited to send observers to the meeting. This paper is a resumeÂ of some of the main points presented and discussed during the 2 days.

Optimal treatments for patients with bleeding disorders.

Ventriculomegaly: evaluation and management.

The International Network for Pediatric Hemophilia (INPH) comprises a group of physicians committed to the unique care of and challenges facing pediatric hemophilia patients. By collaborating on an international level, extensive experience can be shared on current practice, new trends can be discussed and scientifically valid studies can be developed and performed. The three overall objectives of the group (scientific progress, education and networking) are achieved at each annual meeting starting with a round table on the members' current research and clinical activities, project reports of INPH study initiatives, followed by invited educational presentations and interactive discussions. The meetings close with proposals of new projects, future directions of the group and concluding remarks. The Fourth Annual INPH meeting, held in 2009 in Boston, MA, USA, focused on inhibitor development and hemophilic arthropathy in the clinical care of children with hemophilia.

/pdf/the-fourth-annual-meeting-of-the-international-network-for-2xyid1z5bp.pdf

The Fourth Annual Meeting of the International Network for Pediatric Hemophilia: Current Challenges and Recommendations in the Clinical Care of Children with Hemophilia.

M L Manco-Johnson

Papers

Kleeblattschadel anomaly: in utero sonographic appearance

Optimal treatments for patients with bleeding disorders.

Ventriculomegaly: evaluation and management.

The Fourth Annual Meeting of the International Network for Pediatric Hemophilia: Current Challenges and Recommendations in the Clinical Care of Children with Hemophilia.

Long-Term Orthopedic Effects Of Delaying Prophylaxis In Severe Hemophilia A Until Age 6 Years: Results Of The Joint Outcome Study Continuation (JOSc)