Posterior cortical atrophy as a primary clinical phenotype of corticobasal syndrome with a progranulin gene rs5848 TT genotype
Posterior cortical atrophy (PCA) represents a special clinicoradiologic syndrome characterized by progressive visuospatial and visuoperceptual deficits. PCA and corticobasal syndrome (CBS) may share similar pa... (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - February 6, 2016 Category: Internal Medicine Authors: Guoping Peng, Ping Liu, Fangping He and Benyan Luo Source Type: research

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study
There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening r... (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - February 3, 2016 Category: Internal Medicine Authors: Maria D. Karaceper, Pranesh Chakraborty, Doug Coyle, Kumanan Wilson, Jonathan B. Kronick, Steven Hawken, Christine Davies, Marni Brownell, Linda Dodds, Annette Feigenbaum, Deshayne B. Fell, Scott D. Grosse, Astrid Guttmann, Anne-Marie Laberge, Aizeddin Mh Source Type: research

Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions
Conclusions: Automated depletion of CD45RA+ naïve T-cells from unmobilized whole blood is a simple and rapid strategy to provide unmanipulated DLIs, with a potentially broad repertoire of pathogen specific memory T-cells. In the haploidentical setting, CD45RA+ depleted DLIs can be safely administered at low T-cell doses for efficient enhancement of viral immunity and limited risk of GvHD. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - January 15, 2016 Category: Internal Medicine Authors: Nicholas BrodszkiDominik TurkiewiczJacek ToporskiLennart TruedssonJosefina Dykes Source Type: research

Proteus syndrome: evaluation of the immunological profile
We report on the novel immunologic findings of a 15 years old girl affected with PS. Detailed T and B cell evaluation revealed maturational alterations for both subsets and functional hyperactivation for the latter. Such findings have not been reported previously in PS and may be the spy of more complex immune abnormalities in this syndrome. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - January 13, 2016 Category: Internal Medicine Authors: Vassilios LougarisVincenzo SalpietroMaricia CutrupiManuela BaronioDaniele MorattoM. PizzinoKshitij MankadSilvana BriugliaCarmelo SalpietroAlessandro Plebani Source Type: research

Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis
Conclusions: The possibility to analyze a large number of genes associated with various diseases allows to study cases with phenotypes not well-determined, giving the opportunity to make new genotype-phenotype correlation. In some cases there were discrepancies between clinical features and histology or electron microscopy and only molecular analysis allowed to definitively resolve the diagnostic dilemma. The genetic diagnosis of ichthyosis leads to a more accurate and effective genetic counseling, allowing correct evaluation of the risk of recurrence, particularly in families with consanguineous background. (Source: Orpha...
Source: Orphanet Journal of Rare Diseases - January 13, 2016 Category: Internal Medicine Authors: Andrea DiociaiutiMay El HachemElisa PisaneschiSimona GiancristoforoSilvia GenovesePietro SirletoRenata BoldriniAdriano Angioni Source Type: research

The involvement of patient organisations in rare disease research: a mixed methods study in Australia
Conclusion: This study provides unique information about the experiences of RDPOs generally, rather than experiences retrospectively reported by RDPOs associated with successful research. We describe RDPOs’ valuable contributions to research, while also providing insights into the difficulties for small organisations trying to promote research. The study is relevant internationally because of what it tells us about RDPOs; however, we draw attention to specific opportunities in Australia to support RDPOs’ involvement in research, for the benefit of current and future generations affected by rare diseases. (Sourc...
Source: Orphanet Journal of Rare Diseases - January 12, 2016 Category: Internal Medicine Authors: Deirdre PintoDominique MartinRichard Chenhall Source Type: research

Extending the phenotype of BMPER-related skeletal dysplasias to ischiospinal dysostosis
Ischiospinal dysostosis (ISD) is a polytopic dysostosis characterized by ischial hypoplasia, multiple segmental anomalies of the cervicothoracic spine, hypoplasia of the lumbrosacral spine and occasionally associated with nephroblastomatosis. ISD is similar to, but milder than the lethal/semilethal condition termed diaphanospondylodysostosis (DSD), which is associated with homozygous or compound heterozygous mutations of bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene. Here we report for the first time biallelic BMPER mutations in two patients with ISD, neither of whom had renal abnormalities....
Source: Orphanet Journal of Rare Diseases - January 4, 2016 Category: Internal Medicine Authors: Ekaterina KuchinskayaGiedre GrigelionieneAnna HammarsjöHye-Ran LeeLotta HögbergGintautas GrigelionisOk-Hwa KimGen NishimuraTae-Joon Cho Source Type: research

Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders
Conclusions: Greater efforts should be devoted to improve the methodological quality of guidelines and recommendations for iNMDs and AGREE II instrument seems advisable for new guideline development. The elaboration of new guidelines encompassing still uncovered disorders is badly needed. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 30, 2015 Category: Internal Medicine Authors: Linda CassisElisenda Cortès-SaladelafontMarta Molero-LuisDelia YuberoMaria GonzálezAida HerreroCarme FonsCristina JouCristina SierraEsperanza Castejon PonceFederico RamosJudith ArmstrongM. Mar O¿CallaghanMercedes CasadoRaquel MonteroSilvia OlivasRafael Source Type: research

Special low protein foods for phenylketonuria: availability in Europe and an examination of their nutritional profile
Conclusions: Whilst equal and free access to all SLPF is desirable, the widely variable nutritional composition requires careful nutritional knowledge of all products when prescribed for individual patients with PKU. There is a need for more specific nutritional standards for special low protein foods. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 22, 2015 Category: Internal Medicine Authors: Maria PenaManuela AlmeidaEsther van DamKirsten AhringAmaya Bélanger-QuintanaKatharina DokoupilHulya Gokmen-OzelAnna LammardoAnita MacDonaldMartine RobertJúlio Rocha Source Type: research

A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I
Conclusions: Dystonic patients predominantly showed motor speed impairment, whereas performance improved with higher cognitive load. Patients without motor symptoms did not differ from controls. Developmental functions of cognitive performances were similar in patients and controls. Performance in tests with higher cognitive demand might be preserved in GA-I, even in patients with striatal degeneration. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 22, 2015 Category: Internal Medicine Authors: Nikolas BoyJana HeringerGisela HaegeEsther GlahnGeorg HoffmannSven GarbadeStefan KölkerPeter Burgard Source Type: research

Longitudinal assessment of reflexive and volitional saccades in Niemann-Pick Type C disease during treatment with miglustat
Conclusions: Both qualitative examination of change scores and statistical evaluation with LME analysis support the idea that some saccadic parameters are robust indicators of efficacy, and that the variability observed across measures may indicate locally different effects of neurodegeneration and of drug actions. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 21, 2015 Category: Internal Medicine Authors: Larry AbelMark WalterfangMatthew StainerElizabeth BowmanDennis Velakoulis Source Type: research

Rare diseases and orphan drugs: 500 years ago
In 1581 Rembert Dodoens wrote “Medicinalium observationum exempla rara, recognita et aucta” a Latin book about the diagnosis and treatment of disorders with a low prevalence. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 21, 2015 Category: Internal Medicine Authors: Marc Dooms Source Type: research

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency
Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in t...
Source: Orphanet Journal of Rare Diseases - December 18, 2015 Category: Internal Medicine Authors: Hirsh KomarowRobert SokolicMichael HershfieldDonald KohnMichael YoungDean MetcalfeFabio Candotti Source Type: research

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness
Conclusions: This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 15, 2015 Category: Internal Medicine Authors: Elise Jeannesson-ThivisolFrançois FeilletCéline ChéryPascal PerrinShyue-Fang Battaglia-HsuBernard HerbethAline CanoMagalie BarthAlain FouilhouxKarine MentionFrançois LabartheJean-Baptiste ArnouxFrançois MaillotCatherine LenaertsCécile DumesnilKathy Source Type: research

Neutrophil activation during attacks in patients with hereditary angioedema due to C1-inhibitor deficiency
Background: Earlier studies have shown that the absolute number of neutrophil granulocytes (NGs) may increase during attack of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). Whether NGs undergo activation during attack has not yet been investigated. However, as neutrophil elastase (NE) can cleave and inactivate C1-INH which may contribute to the dysregulation of the kallikrein-kinin system and hence, to edema formation. Our aim was to investigate the possible activation of NGs during attacks. Methods: We studied blood samples obtained from 26 patients with C1-INH-HAE during symptom-free periods and duri...
Source: Orphanet Journal of Rare Diseases - December 10, 2015 Category: Internal Medicine Authors: Nóra VeszeliDorottya CsukaZsuzsanna ZotterÉva ImrehMihály JózsiSzabolcs BenedekLilian VargaHenriette Farkas Source Type: research

Novel grading system for quantification of cystic macular lesions in Usher syndrome
Conclusions: The novel grading system is a reproducible tool for grading OCT images in USH complicated by CML, and potentially could be used for objective tracking of macular pathology in clinical therapy trials. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 10, 2015 Category: Internal Medicine Authors: Ieva SliesoraityteTunde PetoSaddek Mohand-SaidJose Sahel Source Type: research

Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study
Background: Ataxia-telangiectasia (A-T) is a devastating human autosomal recessive disorder that causes progressive cerebellar ataxia, immunodeficiency, premature aging, chromosomal instability and increased cancer risk. Affected patients show growth failure, poor weight gain, low body mass index (BMI), myopenia and increased fatigue during adolescence.The prevalence of alterations in body composition, muscle strength and hormonal status has not been well described in classical A-T patients. Additionally, no current guidelines are available for the assessment and management of these changes. Methods: We analyzed body compo...
Source: Orphanet Journal of Rare Diseases - December 9, 2015 Category: Internal Medicine Authors: H. PommereningS. van DullemenM. KieslichR. SchubertS. ZielenS. Voss Source Type: research

Prevalence, incidence, and age at diagnosis in Marfan Syndrome
Background: Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome.MethodUsing unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977–2014). Following, we confirm...
Source: Orphanet Journal of Rare Diseases - December 2, 2015 Category: Internal Medicine Authors: Kristian GrothHanne HoveKasper KyhlLars FolkestadMette GaustadnesNiels VejlstrupKirstine StochholmJohn ØstergaardNiels AndersenClaus Gravholt Source Type: research

Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers
Conclusions: Our study showed a prevalence of ASD of 40.5 %, confirming the higher risk for this disorder in patients with TSC. However, the severity seems to have a notable variability in TSC patients. Risk factors for ASD are epilepsy, infantile spams, and mutations in TSC2. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 2, 2015 Category: Internal Medicine Authors: Aglaia VignoliFrancesca La BriolaAngela PeronKatherine TurnerChiara VannicolaMonica SaccaniElisabetta MagnaghiGiulia ScornavaccaMaria Canevini Source Type: research

Zellweger spectrum disorders: clinical overview and management approach
Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focu...
Source: Orphanet Journal of Rare Diseases - December 1, 2015 Category: Internal Medicine Authors: Femke KlouwerKevin BerendseSacha FerdinandusseRonald WandersMarc EngelenBwee Poll-The Source Type: research

Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta
Background: Osteogenesis imperfecta (OI) is a congenital disorder characterized by increased bone fragility and low bone mass. Methods: The presence of COL1A1 or COL1A2 mutation was investigated by direct sequencing in 72 patients with OI type I, III, or IV (27 males and 45 females; age range 0.2-62 years) from 37 unrelated families. The clinical features of these patients were also recorded. Results: Thirty-seven COL1A1 and COL1A2 mutations were identified, including 28 COL1A1 mutations and 9 COL1A2 mutations. Fifteen (41 %) were novel mutations, and twelve (32 %) were familial mutations. A review of their medic...
Source: Orphanet Journal of Rare Diseases - December 1, 2015 Category: Internal Medicine Authors: Hsiang-Yu LinChih-Kuang ChuangYi-Ning SuMing-Ren ChenHui-Chin ChiuDau-Ming NiuShuan-Pei Lin Source Type: research

Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers
Background: Up to now, only limited data on long-term medical treatment in congenital hyperinsulinism (CHI) is available. Moreover, most of the drugs used in CHI are therefore not approved. We aimed to assemble more objective information on medical treatment in CHI with regard to type and duration, dosage as well as side effects. Methods: We searched MEDLINE (from 1947) and EMBASE (from 1988) using the OVID interface for relevant data to evaluate medical treatment in a large cohort of patients with CHI from different clinical centers. Randomized, controlled trials were not available. We evaluated case reports and case seri...
Source: Orphanet Journal of Rare Diseases - November 25, 2015 Category: Internal Medicine Authors: Alena WeltersChristian LerchSebastian KummerJan MarquardBurak SalginErtan MayatepekThomas Meissner Source Type: research

High quality, patient centred and coordinated care for Alstrom syndrome: a model of care for an ultra-rare disease
Conclusions: Our study has shown that organised, multidisciplinary “one stop” clinics are patient centred and individually tailored to the patient need with a better outcome and comparable cost compared with the current standard of care for rare disease. Our proposed care model can be adapted to several other rare and ultra-rare diseases. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 24, 2015 Category: Internal Medicine Authors: Stephanie Van GroenendaelLuca GiacovazziFabian DavisonOliver HoltkemperZexin HuangQiaoying WangKay ParkinsonTimothy BarrettTarekegn Geberhiwot Source Type: research

Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth
Conclusions: By using next generation sequencing on a cohort of 38 unrelated families with fetal akinesia/hypokinesia, arthrogryposis, or severe congenital myopathy we therefore obtained a genetic diagnosis for 47 % of families. This study highlights the power and capacity of next generation sequencing (i) to determine the aetiology of genetically heterogeneous neuromuscular diseases, (ii) to identify novel disease genes in small pedigrees or isolated cases and (iii) to refine the interplay between genetic diagnosis and clinical evaluation and management. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 17, 2015 Category: Internal Medicine Authors: Emily ToddKyle YauRoyston OngJennie SleeGeorge McGillivrayChristopher BarnettGoknur HalilogluBeril TalimZuhal AkcorenAriana KariminejadAnita CairnsNigel ClarkeMary-Louise FreckmannNorma RomeroDenise WilliamsCaroline SewryAlison ColleyMonique RyanCathy Kir Source Type: research

The spectrum of KIAA0196 variants, and characterization of a murine knockout: implications for the mutational mechanism in hereditary spastic paraplegia type SPG8
Conclusions: Our data do not support the current view that heterozygous loss of strumpellin/SHRC function leads to haploinsufficiency and, in turn, to HSP. The lethality of homozygous knockout mice, i.e. the effect of complete loss of function, also argues against a dominant negative effect of mutant on wild-type strumpellin in patients. Toxic gain-of-function represents a potential alternative explanation. Confirmation of this therapeutically relevant hypothesis in vivo, however, will require availability of appropriate knockin models. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 16, 2015 Category: Internal Medicine Authors: Amir JahicMukhran KhundadzeNadine JaenischRebecca SchüleSven KlimpeStephan KlebeChristiane FrahmJan KassubekGiovanni StevaninLudger SchölsAlexis BriceChristian HübnerChristian Beetz Source Type: research

Initial report of the osteogenesis imperfecta adult natural history initiative
Background: A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. Methods: The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and ...
Source: Orphanet Journal of Rare Diseases - November 14, 2015 Category: Internal Medicine Authors: Laura TosiMatthew OetgenMarianne FloorMary HuberAnn KennellyRobert McCarterMelanie RakBarbara SimmondsMelissa SimpsonCarole TuckerFergus McKiernan Source Type: research

Bruch’s membrane abnormalities in PRDM5-related brittle cornea syndrome
Conclusions: PDRM5-related disease is known to affect the cornea, skin and joints. Here we demonstrate, to the best of our knowledge for the first time, that PRDM5 localizes not only in the human cornea, but is also widely expressed in the retina. Our findings suggest that ECM abnormalities in PRDM5-associated disease are more widespread than previously reported. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 11, 2015 Category: Internal Medicine Authors: Louise PorterRoberto Gallego-PinazoCatherine KeelingMartyna KamieniorzNicoletta ZoppiMarina ColombiCecilia GiuntaRichard BonshekForbes MansonGraeme Black Source Type: research

Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia
Conclusions: Patients with late infantile metachromatic leukodystrophy exhibited a rapid and devastating clinical course. The pattern of dysmyelination on brain MRI together with peripheral demyelination polyneuropathy indicates that evaluation of ARSA activity in leukocytes is warranted. A wide diversity of ARSA gene mutations was noted in Asia. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 9, 2015 Category: Internal Medicine Authors: Hsiang-Ru LiawHsiu-Fen LeeChing-Shiang ChiChi-Ren Tsai Source Type: research

The effects of intracisternal enzyme replacement versus sham treatment on central neuropathology in preclinical canine fucosidosis
Conclusions: Despite reduced severity of fucosidosis neuropathology with partial enzyme replacement, more complete and sustained biochemical correction is required to halt neuropathological processes in this large animal model of lysosomal storage disease. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 4, 2015 Category: Internal Medicine Authors: Gauthami KondagariJessica FletcherRachel CruzPeter WilliamsonJohn HopwoodRosanne Taylor Source Type: research

Focusing on rare diseases in China: are we there yet?
The Chinese researchers have made significant progress in studying rare diseases in the recent years. From 2000 to 2014, 269 out of 1892 clinically relevant original research papers published on high impact journals by Chinese institutions, and 2678 out of 6040 clinical trials conducted by Chinese institutions and registered at ClinicalTrial.gov are focused on rare diseases. The number of research papers and of clinical trials has shown a steady trend of increase. Creating public databases for rare disease will escalate progress in rare disease and enable multicenter studies. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - November 2, 2015 Category: Internal Medicine Authors: Li YangChang SuAshley LeeHarrison Bai Source Type: research

Effect of systemic high dose enzyme replacement therapy on the improvement of CNS defects in a mouse model of mucopolysaccharidosis type II
Conclusions: These results suggest that high-dose ERT given to mice of earlier ages may play a role in preventing GAG accumulation and preventing CNS damage in IDS KO mice. Therefore, ERT above the present standard dose, starting in early childhood, could be a promising treatment regimen for reducing neurological impairment in Hunter syndrome. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 31, 2015 Category: Internal Medicine Authors: Sung Yoon ChoJeehun LeeAh-Ra KoMin Jung KwakSujin KimYoung Bae SohnSung Won ParkDong-Kyu Jin Source Type: research

Rare genetic disease in China: a call to improve clinical services
No description available (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 29, 2015 Category: Internal Medicine Authors: M. ChopraT. Duan Source Type: research

Review and comparison of clinical evidence submitted to support European Medicines Agency market authorization of orphan-designated oncological treatments
Conclusions: Clinical trials of orphan treatments are often limited by low patient numbers and inadequate follow-up. Pooling of expertise in single centres and the establishment of rare disease reference networks and patient registries may facilitate appropriate trial design for orphan-designated treatments. This analysis found that the pivotal clinical trial for mifamurtide in osteosarcoma had the largest number of patient-years of follow-up, despite a small eligible patient population, showing that it is possible to conduct studies with an adequate patient population size and duration of follow-up in patient-years, and a...
Source: Orphanet Journal of Rare Diseases - October 28, 2015 Category: Internal Medicine Authors: Julie WinstoneShkun ChaddaStephen RalstonPeter Sajosi Source Type: research

Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment
Background: Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS...
Source: Orphanet Journal of Rare Diseases - October 26, 2015 Category: Internal Medicine Authors: Mercedes SerranoVíctor de DiegoJordi MuchartDaniel CuadrasAna FelipeAlfons MacayaRamón VelázquezM. PooCarmen FonsM. O¿CallaghanAngels García-CazorlaCristina BoixBernabé RoblesFrancisco CarrataláMarisa GirósPaz BrionesLaura GortRafael ArtuchCelia P Source Type: research

Mortality-related resource utilization in the inpatient care of hypoplastic left heart syndrome
Background: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF). Methods: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children’s hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21&...
Source: Orphanet Journal of Rare Diseases - October 22, 2015 Category: Internal Medicine Authors: David DanfordQuentin KarelsAparna KulkarniAysha HussainYunbin XiaoShelby Kutty Source Type: research

Immunosuppressive drugs and fertility
Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 21, 2015 Category: Internal Medicine Authors: Clara LeroyJean-Marc RigotMaryse LeroyChristine DecanterKristell Le MapihanAnne-Sophie ParentAnne-Claire Le GuillouIbrahim Yakoub-AghaSébastien DharancyChristian NoelMarie-Christine Vantyghem Source Type: research

47 patients with FLNA associated periventricular nodular heterotopia
Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for ...
Source: Orphanet Journal of Rare Diseases - October 15, 2015 Category: Internal Medicine Authors: Max LangeBurkhard KasperAxel BohringFrank RutschGerhard KlugerSabine HoffjanStephanie SprangerAnne BehneckeAndreas FerbertAndreas HahnBarbara Oehl-JaschkowitzLuitgard Graul-NeumannKatharina DiepoldIsolde SchreyerMatthias BernhardFranziska MuellerUlrike Si Source Type: research

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations
Conclusions: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 15, 2015 Category: Internal Medicine Authors: Sandra MercierSébastien KüryEmmanuelle Salort-CampanaArmelle MagotUchenna AgbimThomas BesnardNathalie BodakChantal Bou-HannaFlora BréhéretPerrine BrunelleFlorence CaillonBrigitte ChabrolValérie Cormier-DaireAlbert DavidBruno EymardLaurence FaivreDomi Source Type: research

Visual evoked potentials of Niemann-Pick type C1 mice reveal an impairment of the visual pathway that is rescued by 2-hydroxypropyl-ß-cyclodextrin
Conclusions: This study pinpoints the analysis of VEP response as a potentially accurate and non-invasive approach to assess neural activity and visual information processing in NPC1 patients, as well as for monitoring the progression of the disease and assessing the efficacy of potential therapies. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 12, 2015 Category: Internal Medicine Authors: Giampiero PalladinoStefano LoizzoAndrea FortunaSonia CanteriniFioretta PalombiRobert EricksonFranco MangiaMaria Fiorenza Source Type: research

Comprehensive study into the activation of the plasma enzyme systems during attacks of hereditary angioedema due to C1-inhibitor deficiency
Background: The activation of plasma enzyme systems contributes to hereditary angioedema attacks. We aimed to study the activation markers of the fibrinolytic, coagulation, and contact systems in a larger number of paired samples obtained from the same C1-INH-HAE patients in symptom-free periods and during attacks. Methods: Eleven parameters (Factors XI, XII, and C1-inhibitor activity; the concentrations of the D-dimer, prothrombin fragments 1 + 2, plasminogen, plasminogen activator inhibitor-1 [PAI-1], thrombin-anti-thrombin III [TAT] complex, fibrinogen) were measured along with prothrombin time and activat...
Source: Orphanet Journal of Rare Diseases - October 9, 2015 Category: Internal Medicine Authors: Dorottya CsukaNóra VeszeliÉva ImrehZsuzsanna ZotterJudit SkopálZoltán ProhászkaLilian VargaHenriette Farkas Source Type: research

Clinical heterogeneity and potential high pathogenicity of the Mmalton Alpha 1 antitrypsin allele at the homozygous, compound heterozygous and heterozygous states
Conclusions: Our study provides another example of Pi Mmalton homozygosity associated with a severe liver disease that emphasizes the necessity of a not delayed diagnosis. The great clinical heterogeneity of the other genotypes (which is in agreement with the literature data) questions about the role of environmental and other modifier genes in the pathogenicity of A1ATD. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 7, 2015 Category: Internal Medicine Authors: Philippe JolyOlivier GuillaudValérie HervieuAlain FrancinaJean-François MornexColette Chapuis-Cellier Source Type: research

Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships
Conclusions: These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 7, 2015 Category: Internal Medicine Authors: Nouriya Al-SannaaLuisa BayDeborah BarbouthYoussef BenhayounCyril GoizetNorberto GuelbertSimon JonesSandra KyosenAna MartinsChanika PhornphutkulCelia ReigRebecca PleatShari FalletIva Ivanovska Holder Source Type: research

Primary erythromelalgia: a review
Primary erythromelalgia (PE ORPHA90026) is a rare autosomal dominant neuropathy characterized by the combination of recurrent burning pain, warmth and redness of the extremities. The incidence rate of PE ranges from 0.36 to 1.1 per 100,000 persons. Gender ratio differs according to different studies and no evidence showed a gender preference. Clinical onset of PE is often in the first decade of life. Burning pain is the most predominant symptom and is usually caused and precipitated by warmth and physical activities. Reported cases of PE contain both inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9...
Source: Orphanet Journal of Rare Diseases - September 30, 2015 Category: Internal Medicine Authors: Zhaoli TangZhao ChenBeisha TangHong Jiang Source Type: research

Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome
Conclusion: Novel mutations and additional phenotypic features expand the genotypic and phenotypic spectrum of 3MC1 syndrome. Although patients with MASP-1 dysfunction in addition to disrupted MASP-3 have an altered complement system, their disease phenotype is not different from those having only MASP-3 dysfunction. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 30, 2015 Category: Internal Medicine Authors: Tahir AtikAsuman KoparirGuney BademciJoseph FosterUmut AltunogluGül MutluSarah BowdinNursel ElciogluGulsen TayfunSevinc AtikMustafa OzenFerda OzkinayYasemin AlanayHulya KayseriliSteffen ThielMustafa Tekin Source Type: research

Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years’ treatment
Conclusions: Approximately 10 years of agalsidase alfa treatment appeared to have beneficial effects for controlling progression and improving some symptoms of Fabry-associated cardiomyopathy. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 29, 2015 Category: Internal Medicine Authors: Christoph KampmannAmandine PerrinMichael Beck Source Type: research

Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms
Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk has been calculated to be 95 % at the age of 65 in one large family, however the frequency of the disorder in the general population is not known and is likely to be less than one in 1,000,000. Oesophageal lesions appear as small (2–5 mm), white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis has also been described. Although symptoms of oesophageal ...
Source: Orphanet Journal of Rare Diseases - September 29, 2015 Category: Internal Medicine Authors: Anthony EllisJanet RiskThiviyani MaruthappuDavid Kelsell Source Type: research

Unmet needs for healthcare and social support services in patients with Huntington’s disease: a cross-sectional population-based study
Conclusions: Needs for healthcare and social services in patients with HD should be assessed in a systematic manner, in order to provide adequate comprehensive care during the course of disease. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 28, 2015 Category: Internal Medicine Authors: Marleen van WalsemEmilie HoweKristin IversenJan FrichNada Andelic Source Type: research

Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood—a study of 155 patients
Background: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. Methods: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. Results: In total, 34 differe...
Source: Orphanet Journal of Rare Diseases - September 26, 2015 Category: Internal Medicine Authors: Eleni PanagiotakakiElisa De GrandisMichela StagnaroErin HeinzenCarmen FonsSanjay SisodiyaBoukje de VriesChristophe GoubauSarah WeckhuysenDavid KemlinkIngrid SchefferGaëtan LescaMuriel RabilloudAmna KlichAlia Ramirez-CamachoAdriana Ulate-CamposJaume Campi Source Type: research

Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome
Conclusions: We generated a new IDUA KO mouse, tested open field, rotarod and grip strength and demonstrated decrease in grip strength, decreased performance and hypo-activity, which may be useful for investigating therapeutic approaches, and studying the pathogenesis of joint and locomotion symptoms in MPS I. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 25, 2015 Category: Internal Medicine Authors: Chihwa KimMin KwakSung ChoAh-ra KoJinguen RheeyJeong-Yi KwonYokyung ChungDong-Kyu Jin Source Type: research

Categorizing diffuse parenchymal lung disease in children
Conclusions: This study provides a suitable workflow and hand-on rules for the categorization of pediatric DPLD. Potential pitfalls were identified and a foundation was laid for the development of consensus-based, international categorization guidelines. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 25, 2015 Category: Internal Medicine Authors: Matthias GrieseArmin IrnstetterMeike HengstHelen BurmesterFelicitas NagelJan RipperMaria FeilckeIngo PawlitaFlorian GotheMatthias KapplerAndrea SchamsTraudl WesselakDaniela RauchThomas WittmannPeter LohseFrank BraschCarolin Kröner Source Type: research