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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Orphanet J Rare Dis · Jan 2014
Multicenter StudyRenal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study.
The Birt-Hogg-Dubé syndrome is a rare cancer susceptibility syndrome characterised by renal tumours, lung cysts and pneumothoraces, and fibrofolliculomas. It is caused by dominantly inherited mutations in FLCN. Our objective was to report renal tumour characteristics in a large series of patients with the Birt-Hogg-Dubé syndrome. ⋯ Age at renal tumour diagnosis was highly variable, highlighting the need for regular surveillance from young adulthood to old age. Most cases had tumour types classically associated with Birt-Hogg-Dubé, i.e. oncocytoma or renal cell carcinoma of the chromophobe or hybrid type. Nevertheless, 9% had clear cell renal cell carcinoma. Geneticists, urologists and oncologists should therefore be alert to the possibility of Birt-Hogg-Dubé in patients with renal cell carcinoma of clear cell histology, especially if there are associated manifestations. Finally, the behaviour of metastatic carcinoma seemed more indolent than in sporadic renal cancers.
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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
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
Case ReportsEffectiveness of cladribine therapy in patients with pulmonary Langerhans cell histiocytosis.
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterised by granulomatous proliferation of CD1a-positive histiocytes forming granulomas within lung parenchyma, in strong association with tobacco smoking, and which may result in chronic respiratory failure. Smoking cessation is considered to be critical in management, but has variable effects on outcome. No drug therapy has been validated. Cladribine (chlorodeoxyadenosine, 2-CDA) down-regulates histiocyte proliferation and has been successful in curbing multi-system Langerhans cell histiocytosis and isolated PLCH. ⋯ Cladribine as a single agent may be effective therapy in patients with progressive PLCH.