Orphanet J Rare Dis
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Orphanet J Rare Dis · Feb 2014
A past with uncertainty, a future with hope--rare disease day 2014 from a USA perspective.
We reflect on the worldwide research accomplishments, orphan product approvals, and the commitments by the rare diseases community. Major collaborative efforts by the public and private sectors increased interventions and diagnostics for rare diseases. ⋯ The global rare diseases community remains strong and responsive to the voices and needs of patients, families, and clinicians awaiting diagnosis and treatment for their disease. We anticipate even greater successes in 2014 to reflect on Rare Disease Day 2015.
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The pricing mechanism of orphan drugs appears arbitrary and has been referred to as a "black box". Therefore, the aim of this study is to investigate how drug- and disease-specific variables relate to orphan drug prices. Additionally, we aim to explore if certain country-specific pricing and reimbursement policies affect the price level of orphan drugs. ⋯ This study has shown that prices of orphan drugs are influenced by factors such as the availability of an alternative drug treatment, repurposing, etc. Current debate about the affordability of orphan drugs highlights the need for more transparency in orphan drug price setting.
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Orphanet J Rare Dis · Jan 2014
Multicenter StudyFunctional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers. ⋯ An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.
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Orphanet J Rare Dis · Jan 2014
Randomized Controlled TrialThe effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7-12 years). ⋯ This is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children.
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Orphanet J Rare Dis · Jan 2014
X-exome sequencing in Finnish families with intellectual disability--four novel mutations and two novel syndromic phenotypes.
X-linked intellectual disability (XLID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, social and behavioral adaptive skills. Next generation sequencing technologies have become a powerful approach for identifying molecular gene mutations relevant for diagnosis. ⋯ All of the mutations found in this study are being reported for the first time in Finnish families with several affected male patients whose etiological diagnoses have remained unknown to us, in some families, for more than 30 years. This study illustrates the impact of X-exome sequencing to identify rare gene mutations and the challenges of interpreting the results. Further functional studies are required to confirm the cause of the syndromic phenotypes associated with ZMYM3 and SYP in this study.