Orphanet Journal of Rare Diseases via MedWorm.com

Gaucher disease and the synucleinopathies: refining the relationship

Orphanet Journal of Rare Diseases — Tue, 31 Jan 2012 05:00:00 +0100

Gaucher disease (OMIM 230800, 230900, 231000), the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. Gaucher patients display a wide spectrum of clinical presentation, with hepatosplenomegaly, haematological changes, and orthopaedic complications being the predominant symptoms. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (non-neuronopathic), Type 2 (acute neuronopathic), and Type 3 (subacute neuronopathic). Nearly 300 mutations have been identified in Gaucher patients, with the majority being missense mutations. Though studies of genotype-to-phenotype correlations have revealed significant heterogeneity, some consistent patterns have emerged to inform prognost...

Endocrine manifestations related to inherited metabolic diseases in adults

Orphanet Journal of Rare Diseases — Sat, 28 Jan 2012 05:00:00 +0100

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficien...

Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

Orphanet Journal of Rare Diseases — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: In summary, this unbiased and time-efficient NGS approach allowed mutation detection in 75% of control cases and in 57% of test cases. Furthermore, it has the possibility of associating known gene defects with novel phenotypes and mode of inheritance. (Source: Orphanet Journal of Rare Diseases)

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Orphanet Journal of Rare Diseases — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: Within the group of "classical" organic acidurias, IVA appears to be exceptional considering its milder neuropathologic implications. The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening. (Source: Orphanet Journal of Rare Diseases)

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

Orphanet Journal of Rare Diseases — Mon, 23 Jan 2012 05:00:00 +0100

Conclusions: In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients. (Source: Orphanet Journal of Rare Diseases)

Clinical expression of Menkes disease in females with normal karyotype

Orphanet Journal of Rare Diseases — Sun, 22 Jan 2012 05:00:00 +0100

Conclusion: The X- inactivation pattern alone cannot be used to predict the phenotypic outcome in female carriers, as even those with skewed X-inactivation of the X-chromosome harbouring the mutation might have neurological symptoms. (Source: Orphanet Journal of Rare Diseases)

ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure

Orphanet Journal of Rare Diseases — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions: : This largest association study undertaken to determine correlation between POF and AANM / EM revealed three significant SNPs (rs2278493, rs2234693, and rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes. (Source: Orphanet Journal of Rare Diseases)

Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI

Orphanet Journal of Rare Diseases — Wed, 11 Jan 2012 05:00:00 +0100

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes sever...

Chromosome 15q24 microdeletion syndrome

Orphanet Journal of Rare Diseases — Wed, 04 Jan 2012 05:00:00 +0100

is a recently described rare microdeletion syndrome that has been reported in 19 individuals. It is characterized by growth retardation, intellectual disability, and distinct facial features including long face with high anterior hairline, hypertelorism, epicanthal folds, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, small mouth, long smooth philtrum, and full lower lip. Other common findings include skeletal and digital abnormalities, genital abnormalities in males, hypotonia, behavior problems, recurrent infections, and eye problems. Other less frequent findings include hearing loss, growth hormone deficiency, hernias, and obesity. Congenital malformations, while rare, can be severe and include structural brain anomalies, cardiov...

Gastric lactobezoar - a rare disorder?

Orphanet Journal of Rare Diseases — Wed, 04 Jan 2012 05:00:00 +0100

In conclusion, gastric lactobezoar is a disorder of unknown prevalence and is nowadays very rarely published, possibly because of inadequate diagnostic sensitivity and/or not yet identified but beneficial modifications of patient management. (Source: Orphanet Journal of Rare Diseases)

Congenital Diaphragmatic Hernia

Orphanet Journal of Rare Diseases — Tue, 03 Jan 2012 05:00:00 +0100

(CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash , Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is (Source: Orphanet Journal of Rare Diseases)

Congenital Dyserythropoietic Anemia Type II: Molecular Analysis and Expression of the SEC23B Gene

Orphanet Journal of Rare Diseases — Fri, 30 Dec 2011 05:00:00 +0100

Conclusions: In this study, we identified four novel SEC23B mutations associated with CDAII disease. We also demonstrate that the genetic alteration results in a significant decrease of SEC23B transcript in erythroid precursors. Similar down-regulation was observed in peripheral lymphocytes, suggesting that the use of these cells might be sufficient in the identification of Sec23B gene alterations. Finally, we demonstrate that decreased Sec23B protein levels in erythroid precursors correlate with down-regulation of the SEC23B mRNA transcript. (Source: Orphanet Journal of Rare Diseases)

Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Orphanet Journal of Rare Diseases — Thu, 29 Dec 2011 05:00:00 +0100

Conclusions: Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI. (Source: Orphanet Journal of Rare Diseases)

A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K

Orphanet Journal of Rare Diseases — Mon, 26 Dec 2011 05:00:00 +0100

Conclusion: Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases. (Source: Orphanet Journal of Rare Diseases)

Population Pharmacokinetics and Pharmacodynamics of Cysteamine in Nephropathic Cystinosis Patients.

Orphanet Journal of Rare Diseases — Fri, 23 Dec 2011 05:00:00 +0100

Conclusions: According to simulations, in order to increase the percentage of patient with cystine levels below 1 nmol hemicystine/mg of protein, the current dosages could be changed as follows: 80 mg/kg/day (QID) from 10 to 17 kg, 70 mg/kg/day (QID) from 17 to 25 kg, 60 mg/kg/day (QID) from 25 to 40 kg and 50 mg/kg/day (QID) from 40 to 70 kg (these dosages remain under the maximum recommended dose). However an 8-hourly daily treatment (TID) did not provide acceptable cystine levels and should not be proposed. (Source: Orphanet Journal of Rare Diseases)

5'UTR mutations of ENG cause Hereditary Hemorrhagic Telangiectasia

Orphanet Journal of Rare Diseases — Thu, 22 Dec 2011 05:00:00 +0100

Conclusions: Our results emphasize the need for the inclusion of the 5'UTR region of ENG in clinical testing for HHT. (Source: Orphanet Journal of Rare Diseases)

Biomarker analysis of Morquio syndrome: Identification of disease state and drug responsive markers

Orphanet Journal of Rare Diseases — Fri, 16 Dec 2011 05:00:00 +0100

Conclusions: Candidate biomarkers alpha-1-antitrypsin, lipoprotein (a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPS VIA patients. (Source: Orphanet Journal of Rare Diseases)

Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nation wide retrospective study.

Orphanet Journal of Rare Diseases — Mon, 12 Dec 2011 05:00:00 +0100

Conclusion: VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication. (Source: Orphanet Journal of Rare Diseases)

Laryngo-tracheo-oesophageal clefts

Orphanet Journal of Rare Diseases — Wed, 07 Dec 2011 05:00:00 +0100

A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx, possibly extending downward between the trachea and the esophagus. The estimated annual incidence of LC is 1/10,000 to 1/20,000 live births, accounting for 0.2% to 1.5% of congenital malformations of the larynx. These incidence rates may however be underestimated due to difficulty in diagnosing minor forms and a high mortality rate in severe forms. A slightly higher incidence has been reported in boys than in girls. No specific geographic distribution has been found. Depending on the severity of the malformation, patients may present with stridor, hoarse cry, swallowing difficulties, aspirations, cough, dyspnea and cyanosis...

Type 1 autoimmune pancreatitis

Orphanet Journal of Rare Diseases — Wed, 07 Dec 2011 05:00:00 +0100

Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diag...

Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects

Orphanet Journal of Rare Diseases — Thu, 01 Dec 2011 05:00:00 +0100

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. Children who have FOP appear normal at birth except for congenital malformations of the great toes. During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups) occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. These flare-ups transform skeletal muscles, tendons, ...

Benefits, Challenges and Obstacles of Adaptive Clinical Trial Designs

Orphanet Journal of Rare Diseases — Wed, 30 Nov 2011 05:00:00 +0100

In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less w...

Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence

Orphanet Journal of Rare Diseases — Mon, 21 Nov 2011 05:00:00 +0100

Conclusions: This patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine. (Source: Orphanet Journal of Rare Diseases)

Coordinated multidisciplinary care for ambulatory Huntington's disease patients. Evaluation of 18 months of implementation.

Orphanet Journal of Rare Diseases — Fri, 18 Nov 2011 05:00:00 +0100

Conclusions. We concluded that coordinating outreaching multidisciplinary care from an outpatient clinic into the dwelling place of the patient is feasible and appreciated. (Source: Orphanet Journal of Rare Diseases)

The hyperimmunoglobulin E syndrome - clinical manifestation diversity in primary immune deficiency

Orphanet Journal of Rare Diseases — Tue, 15 Nov 2011 05:00:00 +0100

The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities - the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impai...

Ancient founder mutation is responsible for Imerslund-Grasbeck Syndrome among diverse ethnicities

Orphanet Journal of Rare Diseases — Sun, 13 Nov 2011 05:00:00 +0100

Conclusions: This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related. (Source: Orphanet Journal of Rare Diseases)

A rare bladder cancer - small cell carcinoma: review and update.

Orphanet Journal of Rare Diseases — Sun, 13 Nov 2011 05:00:00 +0100

Small cell carcinoma of the bladder (SCCB) is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC). Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease (< or = cT1-4aN0M0) should be managed with multimodal therapy associating chemotherapy...

Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour.

Orphanet Journal of Rare Diseases — Thu, 10 Nov 2011 05:00:00 +0100

Conclusions: In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the ATP7A gene. (Source: Orphanet Journal of Rare Diseases)

Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

Orphanet Journal of Rare Diseases — Mon, 07 Nov 2011 05:00:00 +0100

This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies.Take-home message: Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease. (Source: Orphanet Journal of Rare Diseases)

Spinal muscular atrophy

Orphanet Journal of Rare Diseases — Wed, 02 Nov 2011 04:00:00 +0100

(SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 9...

Xeroderma pigmentosum

Orphanet Journal of Rare Diseases — Tue, 01 Nov 2011 04:00:00 +0100

(XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. It is a rare autosomal recessive disorder and has been found in all continents and racial groups. Estimated incidences vary from 1 in 20,000 in Japan to 1 in 250,000 in the USA, and approximately 2.3 per million live births in Western Europe.The first features are either extreme sensitivity to sunlight, triggering severe sunburn, or, in patients who do not show this sun-sensitivity, abnormal lentiginosis (freckle-like pigmentation due to increased numbers of melanocytes) on sun-exposed areas. This is followed by areas of increased or decreased pigmentation, skin aging and multiple skin cancers, if the individuals are not protected from sun...

Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

Orphanet Journal of Rare Diseases — Mon, 31 Oct 2011 04:00:00 +0100

Conclusions: No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activity. (Source: Orphanet Journal of Rare Diseases)

Neuroacanthocytosis Syndromes

Orphanet Journal of Rare Diseases — Tue, 25 Oct 2011 04:00:00 +0100

Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome which have a Huntington's disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's...

Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

Orphanet Journal of Rare Diseases — Mon, 24 Oct 2011 04:00:00 +0100

Conclusions: This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore, SMS analogues appear to be less effective for treating genetic somatotropinoma than sporadic somatotropinoma. (Source: Orphanet Journal of Rare Diseases)

Mutational screening of the USH2A gene in Spanish patients reveals 23 novel pathogenic mutations

Orphanet Journal of Rare Diseases — Mon, 17 Oct 2011 04:00:00 +0100

Conclusions: This report provide a wide spectrum of USH2A mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin. (Source: Orphanet Journal of Rare Diseases)

Therapy of Fabry disease with pharmacological chaperones: from in silico predictions to in vitro tests

Orphanet Journal of Rare Diseases — Mon, 17 Oct 2011 04:00:00 +0100

Conclusions: In this paper we provide experimental support to an "in silico" method designed to predict missense mutations in the gene encoding lysosomal alpha galactosidase responsive to pharmacological chaperones. We demonstrated that responsive mutations can be predicted with a low percentage of false positive cases. Most of the mutations tested to validate the method were described in the literature as associated to classic or mild classic phenotype. The analysis can provide a guideline for the therapy with pharmacological chaperones supported by experimental results obtained in vitro. We are aware that our results were obtained in vitro and cannot be translated straightforwardly into benefit for patients, but need to be validated by clinical trials. (Source: Orphanet Journal of Rare D...

Congenital Hyperinsulinism: Current Trends in Diagnosis and Therapy

Orphanet Journal of Rare Diseases — Mon, 03 Oct 2011 04:00:00 +0100

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic beta-cells secondary to various genetic disorders. The incidence is estimated at 1/50,000 live births, but it may be as high as 1/2,500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions ...

Population-based evaluation of a suggested anatomic and clinical classification of congenital heart defects based on the International Paediatric and Congenital Cardiac Code.

Orphanet Journal of Rare Diseases — Mon, 03 Oct 2011 04:00:00 +0100

Conclusion: Our proposed classification is not new, but rather a regrouping of the known spectrum of CHD into a manageable number of categories based on anatomic and clinical criteria. The classification is designed to use the code numbers of the long list of IPCCC but can accommodate ICD-10 codes. Its exhaustiveness, simplicity, and anatomic basis make it useful for clinical and epidemiologic studies, including those aimed at assessment of risk factors and outcomes. (Source: Orphanet Journal of Rare Diseases)

Estimating the budget impact of orphan medicines in Europe: 2010 - 2020

Orphanet Journal of Rare Diseases — Tue, 27 Sep 2011 04:00:00 +0100

Conclusions: Although European orphan drug legislation has led to an increase in the number of approved orphan drugs, the growth in cost, as a proportion of total pharmaceutical expenditure, is likely to plateau over the next decade as orphan growth rates converge on those in the broader pharmaceutical market. Given the assumptions and simplifications inherent in such a projection, there is uncertainty around the base case forecast and further research is needed to monitor how trends develop. However, fears that growth in orphan drug expenditure will lead to unsustainable cost escalation do not appear to be justified. Furthermore, based on the results of this budget impact forecast, the European orphan drug legislation is not leading to a disproportionate impact on pharmaceutical expenditu...

Reducing Selection Bias in Case-Control Studies from Rare Disease Registries.

Orphanet Journal of Rare Diseases — Mon, 12 Sep 2011 04:00:00 +0100

Conclusions: We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries. (Source: Orphanet Journal of Rare Diseases)

Atypical hemolytic uremic syndrome

Orphanet Journal of Rare Diseases — Thu, 08 Sep 2011 04:00:00 +0100

Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10 % of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% di...

Does market exclusivity hinder the development of Follow-on Orphan Medicinal Products in Europe?

Orphanet Journal of Rare Diseases — Mon, 05 Sep 2011 04:00:00 +0100

Conclusions: This study provides evidence that absence of follow-on OMP development is a matter of time or market size, rather than that the market exclusivity incentive of the European Orphan Drug Regulation creates a market monopoly. (Source: Orphanet Journal of Rare Diseases)

Two new Rett syndrome families and review of the literature: expanding the knowledge of MECP2 frameshift mutations

Orphanet Journal of Rare Diseases — Mon, 29 Aug 2011 23:00:00 +0100

Conclusions: The present study suggests a correlation between the intrafamilial phenotypic differences observed in RTT families and their respective XCI pattern in blood, in contrast to sporadic RTT cases where a similar correlation has not been demonstrated. Furthermore, we found de novo MECP2 frameshift mutations frequently to be of paternal origin, although not with the same high paternal occurrence as in sporadic cases with C to T transitions. This suggests further investigations of more families. This study emphasizes the need for thorough genetic counselling of families with a newly diagnosed RTT patient. (Source: Orphanet Journal of Rare Diseases)

Awakening Australia to Rare Diseases: Symposium report and preliminary outcomes

Orphanet Journal of Rare Diseases — Wed, 17 Aug 2011 23:00:00 +0100

Western Australia recently hosted Australia's inaugural national rare disease symposium, entitled Awakening Australia to Rare Diseases: Global perspectives on establishing a coordinated approach to a national plan (www.raredisease.com.au) in the port city of Fremantle, Western Australia from the 17th-20th of April 2011.The Office of Population Health Genomics (OPHG), Department of Health Western Australia, in conjunction with the Australian Paediatric Surveillance Unit (APSU), initiated the Symposium and established National and Local Organizing Committees to compose a program that included plenary sessions of invited speakers followed by small group discussions to explore issues raised in the formal presentations. The sessions and content were informed by the Western Australian supporting...

VACTERL/VATER Association

Orphanet Journal of Rare Diseases — Mon, 15 Aug 2011 23:00:00 +0100