1,604 results match your criteria Orphanet Journal of Rare Diseases [Journal]


Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.

Orphanet J Rare Dis 2019 Feb 15;14(1):44. Epub 2019 Feb 15.

Dietetic Department, Birmingham Childrens Hospital, Steelhouse Lane, Birmingham, B4 6 NH, UK.

In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined.

Aim: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. Read More

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http://dx.doi.org/10.1186/s13023-019-1011-yDOI Listing
February 2019

Next generation sequencing identified two novel mutations in NIPBL and a frame shift mutation in CREBBP in three Chinese children.

Orphanet J Rare Dis 2019 Feb 15;14(1):45. Epub 2019 Feb 15.

Center for Medical Genetics, School of life sciences, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, People's Republic of China.

Background: Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RSTS) are both rare congenital multiple malformation disorders caused by genes associated with transcription. They share a number of similar features clinically. In addition, it is difficult to make a molecular diagnosis rapidly and detect the mosaic mutation when only sanger sequencing is taken. Read More

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http://dx.doi.org/10.1186/s13023-019-1022-8DOI Listing
February 2019

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients.

Orphanet J Rare Dis 2019 Feb 14;14(1):43. Epub 2019 Feb 14.

Department of Neurology, Peking University First Hospital, 8 Xishiku St, Xicheng District, Beijing, 100034, China.

Background: Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG, SGCA, SGCB, and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them. Read More

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http://dx.doi.org/10.1186/s13023-019-1021-9DOI Listing
February 2019

Systematic literature review and meta-analysis on the epidemiology of propionic acidemia.

Orphanet J Rare Dis 2019 Feb 13;14(1):40. Epub 2019 Feb 13.

Syreon Research Institute, Mexikói str. 65/A, Budapest, H-1142, Hungary.

Propionic acidemia (PA, OMIM #606054) is a serious, life-threatening, inherited, metabolic disorder caused by the deficiency of the mitochondrial enzyme propionyl-coenzyme A (CoA) carboxylase (EC 6.4.1. Read More

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http://dx.doi.org/10.1186/s13023-018-0987-zDOI Listing
February 2019

Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis.

Orphanet J Rare Dis 2019 Feb 13;14(1):39. Epub 2019 Feb 13.

Department of Pharmacy, Peking University First Hospital, 6 Dahongluochang Street, Xicheng District, Beijing, 100034, China.

Background: The treatment of tuberous sclerosis complex (TSC) using mammalian target of rapamycin (mTOR) inhibitors is clinically promising. The aim of the present study was to evaluate the efficacy and safety of mTOR inhibitors for improving the clinical symptoms of TSC.

Methods: We performed a systematic search of major electronic databases (PubMed, EMBASE, Cochrane Library and WanFang, CNKI, and VIP databases) to identify randomized controlled trials (RCTs) and quasi-randomized studies from the date of database inception to November 2017; the Chinese Food and Drug Administration and clinicaltrials. Read More

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http://dx.doi.org/10.1186/s13023-019-1012-xDOI Listing
February 2019

Mimicry and well known genetic friends: molecular diagnosis in an Iranian cohort of suspected Bartter syndrome and proposition of an algorithm for clinical differential diagnosis.

Orphanet J Rare Dis 2019 Feb 13;14(1):41. Epub 2019 Feb 13.

Genome Research Division, Human Genetics department, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525KL, Nijmegen, The Netherlands.

Background: Bartter Syndrome is a rare, genetically heterogeneous, mainly autosomal recessively inherited condition characterized by hypochloremic hypokalemic metabolic alkalosis. Mutations in several genes encoding for ion channels localizing to the renal tubules including SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, MAGED2 and CASR have been identified as underlying molecular cause. No genetically defined cases have been described in the Iranian population to date. Read More

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http://dx.doi.org/10.1186/s13023-018-0981-5DOI Listing
February 2019

Systematic thyroid screening in myotonic dystrophy: link between thyroid volume and insulin resistance.

Orphanet J Rare Dis 2019 Feb 13;14(1):42. Epub 2019 Feb 13.

CHU Lille, Endocrinology, Diabetology and Metabolism, F-59000, Lille, France.

Background: Myotonic dystrophy (DM1), a neuromuscular disease related to DMPK gene mutations, is associated to endocrine disorders and cancer. A routine endocrine work-up, including thyroid ultrasound (US), was conducted in 115 genetically-proven DM1 patients in a neuromuscular reference center. The aim of this study was to determine the prevalence and the causes of US thyroid abnormalities in DM1. Read More

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http://dx.doi.org/10.1186/s13023-019-1019-3DOI Listing
February 2019

The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy.

Orphanet J Rare Dis 2019 Feb 11;14(1):38. Epub 2019 Feb 11.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany.

Background: The TUBA1A-associated tubulinopathy is clinically heterogeneous with brain malformations, microcephaly, developmental delay and epilepsy being the main clinical features. It is an autosomal dominant disorder mostly caused by de novo variants in TUBA1A.

Results: In three individuals with developmental delay we identified heterozygous de novo missense variants in TUBA1A using exome sequencing. Read More

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http://dx.doi.org/10.1186/s13023-019-1020-xDOI Listing
February 2019

Functional exercise capacity, strength, balance and motion reaction time in Barth syndrome.

Orphanet J Rare Dis 2019 Feb 11;14(1):37. Epub 2019 Feb 11.

Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.

Background: Barth syndrome (BTHS) is an X-linked disorder caused by defects in TAZ with key clinical features including cardiomyopathy, neutropenia and skeletal myopathy. In order to gain a better understanding of the range of clinical features, identify targets for monitoring, and increase knowledge of natural history of the disease, we conducted muscle strength testing, functional exercise capacity testing, physical activity assessment, balance assessment and motion reaction time testing in 33 affected individuals and 14 controls. We analyzed data points to provide a cross-sectional quantitative spectrum of disease characteristics. Read More

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http://dx.doi.org/10.1186/s13023-019-1006-8DOI Listing
February 2019

Regulatory strategies for rare diseases under current global regulatory statutes: a discussion with stakeholders.

Orphanet J Rare Dis 2019 Feb 8;14(1):36. Epub 2019 Feb 8.

Amicus Therapeutics, Inc., 1 Cedar Brook Drive, Cranbury, NJ, 08512, USA.

Rare or orphan diseases often are inherited and overwhelmingly affect children. Many of these diseases have no treatments, are incurable, and have a devastating impact on patients and their families. Regulatory standards for drug approval for rare diseases must ensure that patients receive safe and efficacious treatments. Read More

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http://dx.doi.org/10.1186/s13023-019-1017-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368795PMC
February 2019

Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal.

Orphanet J Rare Dis 2019 Feb 8;14(1):33. Epub 2019 Feb 8.

Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

Background: MNGIE is a rare and fatal disease in which absence of the enzyme thymidine phosphorylase induces systemic accumulation of thymidine and deoxyuridine and secondary mitochondrial DNA alterations. Gastrointestinal (GI) symptoms are frequently reported in MNGIE patients, however, they are not resolved with the current treatment interventions. Recently, our understanding of the GI pathology has increased, which rationalizes the pursuit of more targeted therapeutic strategies. Read More

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http://dx.doi.org/10.1186/s13023-019-1016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368792PMC
February 2019

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series.

Orphanet J Rare Dis 2019 Feb 8;14(1):34. Epub 2019 Feb 8.

Pfizer Inc., Collegeville, PA, USA.

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e. Read More

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http://dx.doi.org/10.1186/s13023-019-1000-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368811PMC
February 2019
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Primary pulmonary lymphoma in children.

Orphanet J Rare Dis 2019 Feb 8;14(1):35. Epub 2019 Feb 8.

Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, Nanlishi Road 56, Xicheng District, Beijing, China.

Background: Primary pulmonary lymphoma (PPL) is a rare disease, especially in children. We analyse the clinical features of PPL in 4 children to strengthen a understanding of it.

Results: We reported a case series of 4 pediatric patients with PPLs including three diffuse large B-cell lymphomas and one natural killer-T cell lymphoma. Read More

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http://dx.doi.org/10.1186/s13023-019-1009-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368794PMC
February 2019
1 Read

Disease progression in women with X-linked adrenoleukodystrophy is slow.

Orphanet J Rare Dis 2019 Feb 7;14(1):30. Epub 2019 Feb 7.

Department of Pediatric Neurology/Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: Over 80% of women with X-linked adrenoleukodystrophy (ALD) develop spinal cord disease in adulthood for which treatment is supportive only. For future clinical trials quantitative data on disease progression rates are essential. Moreover, diagnosis can be challenging in ALD women, as the most important diagnostic biomarker is normal in 15-20%. Read More

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http://dx.doi.org/10.1186/s13023-019-1008-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367840PMC
February 2019

Clinical and mutation profile of pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: results from a Chinese cohort.

Orphanet J Rare Dis 2019 Feb 7;14(1):29. Epub 2019 Feb 7.

Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

Background: The RASopathies are a class of developmental disorders caused by germline mutations in the RAS-mitogen-activated protein kinase (MAPK) pathway. Hypertrophic cardiomyopathy (HCM) has been frequently described in children with RASopathy, but only a minority of patients have received formal genotyping. The purpose of this study was to evaluate the genetic basis and clinical outcome of pediatric patients with RASopathy-associated HCM. Read More

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http://dx.doi.org/10.1186/s13023-019-1010-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367752PMC
February 2019
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Disease characteristics, prognosis and miglustat treatment effects on disease progression in patients with Niemann-Pick disease Type C: an international, multicenter, retrospective chart review.

Orphanet J Rare Dis 2019 Feb 7;14(1):32. Epub 2019 Feb 7.

Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Read More

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http://dx.doi.org/10.1186/s13023-019-0996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367842PMC
February 2019
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The patient's view on rare disease trial design - a qualitative study.

Orphanet J Rare Dis 2019 Feb 7;14(1):31. Epub 2019 Feb 7.

Pediatric clinical Research Office, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.

Background: Clinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a 'classical' Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. Read More

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http://dx.doi.org/10.1186/s13023-019-1002-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367834PMC
February 2019
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Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia.

Orphanet J Rare Dis 2019 Feb 4;14(1):28. Epub 2019 Feb 4.

VASCERN HHT Reference Center, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, and Vascular Sciences, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular dysplasia that leads to nosebleeds and visceral arteriovenous malformations (AVMs). Anti-angiogenic drugs thalidomide and bevacizumab have been increasingly used off-label with variable results. The HHT working group within the ERN for Rare Multisystemic Vascular Diseases (VASCERN), developed a questionnaire-based retrospective capture of adverse events (AEs) classified using the Common Terminology Criteria for Adverse Events. Read More

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http://dx.doi.org/10.1186/s13023-018-0982-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360670PMC
February 2019
1 Read

Advancing the pathologic phenotype of giant axonal neuropathy: early involvement of the ocular lens.

Orphanet J Rare Dis 2019 Feb 1;14(1):27. Epub 2019 Feb 1.

Gene Therapy Center, University of North Carolina at Chapel Hill Chapel Hill, Chapel Hill, NC, USA.

Giant axonal neuropathy (GAN; ORPHA: 643; OMIM# 256850) is a rare, hereditary, pediatric neurodegenerative disorder associated with intracellular accumulations of intermediate filaments (IFs). GAN knockout (KO) mouse models mirror the IF dysregulation and widespread nervous system pathology seen in human GAN. Validation of therapeutic efficacy and viral vector delivery systems with these GAN KO models has provided the springboard for the development of a viral vector being delivered intrathecally in an ongoing Phase I gene therapy clinical trial for the treatment of children with GAN ( https://clinicaltrials. Read More

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http://dx.doi.org/10.1186/s13023-018-0957-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359799PMC
February 2019

Hemophilia carrier's awareness, diagnosis, and management in emerging countries: a cross-sectional study in Côte d'Ivoire (Ivory Coast).

Orphanet J Rare Dis 2019 Feb 1;14(1):26. Epub 2019 Feb 1.

Hemostasis and Thrombosis Unit, Division of Hematology, Cliniques universitaires Saint-Luc, Brussels, Belgium.

Background: Little data is available on awareness of hemophilia carrier condition or associated bleeding risk and management in Sub-Saharan African countries. This study sought to identify hemophilia carriers in Côte d'Ivoire in order to collect data on demographics, bleeding phenotype, and laboratory results. Another purpose was to provide Ivorian hemophilia carriers with counseling on their risk of bleeding and of having children with hemophilia. Read More

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http://dx.doi.org/10.1186/s13023-019-1005-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359866PMC
February 2019
1 Read

Incidental screen positive findings in a prospective cohort study in Matlab, Bangladesh: insights into expanded newborn screening for low-resource settings.

Orphanet J Rare Dis 2019 Jan 30;14(1):25. Epub 2019 Jan 30.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, K1Y 4E9, Canada.

Background: Newborn screening programs are essential preventative public health initiatives but are not widely available in low-resource settings. The objective of this study was to describe the frequency and nature of screen positive determinations as made by a Canadian newborn screening program in a cohort of infants born in Matlab, Bangladesh. Dried newborn cord and heel-prick blood spot samples collected as part of a validation study nested within a preterm birth research cohort were collected between January 2017 and July 2018 and analyzed in a Canadian newborn screening laboratory where the laboratory's disease panel and screening thresholds were applied. Read More

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http://dx.doi.org/10.1186/s13023-018-0993-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354381PMC
January 2019
1 Read

Profiling of patient-specific myocytes identifies altered gene expression in the ophthalmoplegic subphenotype of myasthenia gravis.

Orphanet J Rare Dis 2019 Jan 29;14(1):24. Epub 2019 Jan 29.

Neurology Research Group, Division of Neurology, E8-30, New Groote Schuur Hospital, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.

Background: While extraocular muscles are affected early in myasthenia gravis (MG), but respond to treatment, we observe a high incidence of treatment-resistant ophthalmoplegia (OP-MG) among MG subjects with African genetic ancestry. Previously, using whole exome sequencing, we reported potentially functional variants which associated with OP-MG. The aim of this study was to profile the expression of genes harbouring the OP-MG associated variants using patient-derived subphenotype-specific 'myocyte' cultures. Read More

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http://dx.doi.org/10.1186/s13023-019-1003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352355PMC
January 2019

Assessing disease experience across the life span for individuals with osteogenesis imperfecta: challenges and opportunities for patient-reported outcomes (PROs) measurement: a pilot study.

Orphanet J Rare Dis 2019 Jan 29;14(1):23. Epub 2019 Jan 29.

College of Medicine, University of South Florida, Tampa, Florida, USA.

Background: Patient reported outcome (PRO) information is crucial for establishing better patient-provider communication, improving shared decision-making between clinicians and patients, assessing patient responses to therapeutic interventions, and increasing satisfaction with care. We used the Brittle Bones Disease Consortium (BBDC) Contact Registry for People with OI, managed by the Rare Disease Clinical Research Network (RDCRN) to (1) to evaluate the construct validity of the Patient-Reported Outcome Measurement Information System® (PROMIS®) to record important components of the disease experience among individuals with OI; and (2) explore the feasibility of using a registry to recruit individuals with OI to report on health status. Our long-term goal is to enhance communication of health and disease management findings back to the OI community, especially those who do not have access to major OI clinical centers. Read More

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http://dx.doi.org/10.1186/s13023-019-1004-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350324PMC
January 2019

Cardiac and autonomic function in patients with Wilson's disease.

Orphanet J Rare Dis 2019 Jan 28;14(1):22. Epub 2019 Jan 28.

Department for Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307, Dresden, Germany.

Background: The clinical effect of copper accumulation on the heart of patients suffering from Wilson's disease (WD) is not completely understood. We aimed to determine if patients with WD show signs of cardiac involvement, structural heart disease or autonomic dysfunction. In this prospective trial, we studied 61 patients (mean age 44. Read More

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http://dx.doi.org/10.1186/s13023-019-1007-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348666PMC
January 2019

Patient involvement in medical research: what patients and physicians learn from each other.

Orphanet J Rare Dis 2019 Jan 24;14(1):21. Epub 2019 Jan 24.

Division of Rheumatology and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, White Building, 5th Floor 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Background: There is increasing interest in actively involving patients in the process of medical research to help ensure research is relevant and important to both researchers and people affected by the disease under study. This project examined the recently formed Vasculitis Patient-Powered Research Network (VPPRN), a rare disease research network, to better understand what investigators and patients learned from working on research teams together.

Methods: Qualitative interviews were conducted by phone with patients, physician/PhD-investigators, and study managers/staff who participated in the network. Read More

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http://dx.doi.org/10.1186/s13023-018-0969-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346573PMC
January 2019

Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Orphanet J Rare Dis 2019 Jan 21;14(1):20. Epub 2019 Jan 21.

University of Pretoria, Pretoria, South Africa.

Background: Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. Read More

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http://dx.doi.org/10.1186/s13023-018-0985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341610PMC
January 2019
1 Read

Tracking sex-dependent differences in a mouse model of CLN6-Batten disease.

Orphanet J Rare Dis 2019 Jan 21;14(1):19. Epub 2019 Jan 21.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Background: CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression.

Results: A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Read More

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http://dx.doi.org/10.1186/s13023-019-0994-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341540PMC
January 2019

SMArtCARE - A platform to collect real-life outcome data of patients with spinal muscular atrophy.

Orphanet J Rare Dis 2019 Jan 21;14(1):18. Epub 2019 Jan 21.

Department of Neuropediatrics and Muscle Disorders, Medical Center- University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Survival and quality of life for patients affected by spinal muscular atrophy (SMA) are thought to have improved over the last decade due to changes in care. In addition, targeted treatments for SMA have been developed based on a better understanding of the molecular pathology. In 2016 and 2017, nusinersen was the first drug to be approved for treatment of all types of SMA in the United States and in Europe based on well-controlled clinical trials in a small subgroup of pediatric SMA patients. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-0
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http://dx.doi.org/10.1186/s13023-019-0998-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341722PMC
January 2019
2 Reads

Treatment of thoracolumbar kyphosis in patients with mucopolysaccharidosis type I: results of an international consensus procedure.

Orphanet J Rare Dis 2019 Jan 18;14(1):17. Epub 2019 Jan 18.

Amsterdam UMC, University of Amsterdam, Pediatric Metabolic Diseases, Emma Children's Hospital and Amsterdam Lysosome Center "Sphinx", Meibergdreef 9, Amsterdam, Netherlands.

Background: In all patients with mucopolysaccharidosis type I (MPS I), skeletal disease (dysostosis multiplex) is a prominent, debilitating, condition related complication that may impact strongly on activities of daily living. Unfortunately, it is not alleviated by treatment with hematopoietic cell transplantation (HCT) or enzyme replacement therapy (ERT). Although early kyphosis is one of the key features of dysostosis multiplex, there is no international consensus on the optimal management. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-0
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http://dx.doi.org/10.1186/s13023-019-0997-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339313PMC
January 2019
8 Reads

Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study.

Orphanet J Rare Dis 2019 Jan 14;14(1):16. Epub 2019 Jan 14.

Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

Background: Knowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y).

Methods: This study is a nationwide cohort study in a public health care system. Read More

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http://dx.doi.org/10.1186/s13023-018-0976-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332849PMC
January 2019
4 Reads

Infection risk among adults with down syndrome: a two group series of 101 patients in a tertiary center.

Orphanet J Rare Dis 2019 Jan 11;14(1):15. Epub 2019 Jan 11.

Department of Clinical Immunology and Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, 1, place de l'Hôpital, 67091, Strasbourg, France.

Background: Down syndrome (DS) is the most common form of viable chromosomal abnormality. DS is associated with recurrent infections, auto-immunity and malignancies in children. Little is known about immunity and infections in DS at adulthood. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0989-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329099PMC
January 2019
5 Reads

Clinical and positron emission tomography responses to long-term high-dose interferon-α treatment among patients with Erdheim-Chester disease.

Orphanet J Rare Dis 2019 Jan 10;14(1):11. Epub 2019 Jan 10.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuai Fu Yuan Hu Tong, Dongcheng District, Beijing, 100730, China.

Background: Erdheim-Chester disease (ECD) is a rare multi-systemic form of histiocytosis. Treatment with BRAF inhibitors has markedly improved outcomes of ECD; however, this targeted therapy is expensive (estimated annual cost is $50,000). Since estimated annual cost of interferon-α (IFN-α) is only approximately $1600 in China, we retrospectively evaluated the long-term therapeutic efficacy of IFN-α and the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an assessment method among 32 ECD patients who received high dose IFN-α therapy at Peking Union Medical College Hospital. Read More

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http://dx.doi.org/10.1186/s13023-018-0988-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327591PMC
January 2019
1 Read

Freeman-Burian syndrome.

Orphanet J Rare Dis 2019 Jan 10;14(1):14. Epub 2019 Jan 10.

FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, USA.

Clinical Description: Freeman-Burian syndrome (FBS) is a rare congenital myopathic craniofacial syndrome. Considerable variability in severity is seen, but diagnosis requires the following: microstomia, whistling-face appearance (pursed lips), H or V-shaped chin defect, and prominent nasolabial folds. Some patients do not have limb malformations, but essentially all do, typically camptodactyly with ulnar deviation of the hand and talipes equinovarus. Read More

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http://dx.doi.org/10.1186/s13023-018-0984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327538PMC
January 2019
5 Reads
3.358 Impact Factor

DeepNEU: cellular reprogramming comes of age - a machine learning platform with application to rare diseases research.

Authors:
Wayne R Danter

Orphanet J Rare Dis 2019 Jan 10;14(1):13. Epub 2019 Jan 10.

123Genetix, 147 Chesham Ave, London, ON, N6G 3V2, Canada.

Background: Conversion of human somatic cells into induced pluripotent stem cells (iPSCs) is often an inefficient, time consuming and expensive process. Also, the tendency of iPSCs to revert to their original somatic cell type over time continues to be problematic. A computational model of iPSCs identifying genes/molecules necessary for iPSC generation and maintenance could represent a crucial step forward for improved stem cell research. Read More

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http://dx.doi.org/10.1186/s13023-018-0983-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327463PMC
January 2019
4 Reads

Estimating the clinical cost of drug development for orphan versus non-orphan drugs.

Orphanet J Rare Dis 2019 Jan 10;14(1):12. Epub 2019 Jan 10.

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.

Background: High orphan drug prices have gained the attention of payers and policy makers. These prices may reflect the need to recoup the cost of drug development from a small patient pool. However, estimates of the cost of orphan drug development are sparse. Read More

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http://dx.doi.org/10.1186/s13023-018-0990-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327525PMC
January 2019
1 Read

An ontological foundation for ocular phenotypes and rare eye diseases.

Orphanet J Rare Dis 2019 Jan 9;14(1). Epub 2019 Jan 9.

Centre for Rare Eye Diseases CARGO, SENSGENE FSMR Network, Strasbourg University Hospital, Strasbourg, France.

Background: The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Read More

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http://dx.doi.org/10.1186/s13023-018-0980-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327432PMC
January 2019
1 Read

Cardiac profile of the Czech population of Duchenne muscular dystrophy patients: a cardiovascular magnetic resonance study with T1 mapping.

Orphanet J Rare Dis 2019 Jan 9;14(1):10. Epub 2019 Jan 9.

International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.

Background: The progressive cardiomyopathy that develops in boys with Duchenne and Becker muscular dystrophy (DMD/BMD) is presumed to be a secondary consequence of the fibrosis within the myocardium. There are only limited data on using parametric imaging in these patients. The purpose of this study was to assess native T1 and extracellular volume (ECV) values in DMD patients. Read More

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http://dx.doi.org/10.1186/s13023-018-0986-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327529PMC
January 2019
2 Reads

Experiences in the treatment of refractory chylothorax associated with lymphoproliferative disorders.

Orphanet J Rare Dis 2019 Jan 9;14(1). Epub 2019 Jan 9.

4th Department of Internal Medicine - Hematology, University Hospital, Sokolska Street 581, 5005, Hradec Kralove, Czech Republic.

Background: Chylothorax is a rare condition which can be associated with malignant lymphoproliferative disorders (LPDs). We retrospectively analyzed the results of the conservative treatment of 10 patients with persistent non-traumatic malignant chylothorax.

Results: Conservative treatment lead to a decline of chylothorax after mean of 66 days and consisted of the treatment of the underlying disease and of simultaneous long-term supportive care (drainage of the thoracic cavity, dietary measures and nutrition management). Read More

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http://dx.doi.org/10.1186/s13023-018-0991-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327395PMC
January 2019
1 Read

Nutritional management of phenylalanine hydroxylase (PAH) deficiency in pediatric patients in Canada: a survey of dietitians' current practices.

Orphanet J Rare Dis 2019 Jan 8;14(1). Epub 2019 Jan 8.

McMaster Children's hospital, Hamilton, Ontario, Canada.

Background: Phenylalanine hydroxylase (PAH) deficiency is one of 31 targeted inherited metabolic diseases (IMD) for the Canadian Inherited Metabolic Diseases Research Network (CIMDRN). Early diagnosis and initiation of treatment through newborn screening has gradually shifted treatment goals from the prevention of disabling complications to the optimization of long term outcomes. However, clinical evidence demonstrates that subtle suboptimal neurocognitive outcomes are present in the early and continuously diet-treated population with PAH deficiency. Read More

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http://dx.doi.org/10.1186/s13023-018-0978-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323774PMC
January 2019

Of the importance of the clinical phenotypes in the interpretation of the studies dealing with Fabry disease.

Orphanet J Rare Dis 2019 Jan 7;14(1). Epub 2019 Jan 7.

Sorbonne Université, INSERM, UMR 974, Centre of Research in Myology, Association Institut de Myologie, Pitié-Salpêtrière University Hospital, 75013, Paris, France.

Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies with agalsidase alfa and beta have been available. In this letter we underline the different clinical and technical considerations the readers have to be aware of to interpret the results of studies dealing with Fabry disease and anti-agalsidase antibodies. Read More

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http://dx.doi.org/10.1186/s13023-018-0979-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322341PMC
January 2019
1 Read

Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease.

Orphanet J Rare Dis 2019 Jan 7;14(1). Epub 2019 Jan 7.

Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia.

Background: MicroRNAs (miRNAs) have been associated with the Hirschsprung disease (HSCR) pathogenesis, however, the findings are still inconclusive. We aimed to investigate the effect of miRNA-206 and its targets, fibronectin 1 (FN1), serum deprivation response (SDPR), and paired box 3 (PAX3) expressions on multifactorial HSCR in Indonesia, a genetically distinct group within Asia.

Methods: We determined the miRNA-206, FN1, SDPR and PAX3 expressions in both the ganglionic and aganglionic colon of HSCR patients and control colon by quantitative real-time polymerase chain reaction (qRT-PCR). Read More

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http://dx.doi.org/10.1186/s13023-018-0973-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323865PMC
January 2019
1 Read

Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG.

Orphanet J Rare Dis 2019 Jan 7;14(1). Epub 2019 Jan 7.

Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.

Background: Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated with severe intellectual disability (ID) in a geographically isolated consanguineous family in Northeastern Brazil (Figueredo et al., 2016). Read More

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http://dx.doi.org/10.1186/s13023-018-0977-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322245PMC
January 2019
5 Reads

Genotypic and phenotypic correlations of biotinidase deficiency in the Chinese population.

Orphanet J Rare Dis 2019 Jan 7;14(1). Epub 2019 Jan 7.

Department of Medical Genetics, National Taiwan University Hospital, No. 8, Chung-Shan S. Rd., Zhongzheng Dist., Taipei, 10041, Taiwan.

Biotinidase deficiency is an autosomal recessive disorder that affects the endogenous recycling and release of biotin from dietary protein. This disease was thought to be rare in East Asia. In this report, we delineate the phenotype of biotinidase deficiency in our cohort. Read More

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http://dx.doi.org/10.1186/s13023-018-0992-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323711PMC
January 2019
1 Read

Development of national consensus statements on food labelling interpretation and protein allocation in a low phenylalanine diet for PKU.

Orphanet J Rare Dis 2019 Jan 3;14(1). Epub 2019 Jan 3.

Dietetic Department, Birmingham Women's & Children's NHS Foundation Trust, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.

Background: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients.

Methodology: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Read More

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http://dx.doi.org/10.1186/s13023-018-0950-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318866PMC
January 2019
2 Reads
3.358 Impact Factor

Achondroplasia: a comprehensive clinical review.

Authors:
Richard M Pauli

Orphanet J Rare Dis 2019 Jan 3;14(1). Epub 2019 Jan 3.

Midwest Regional Bone Dysplasia Clinic, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 1500 Highland Ave., Madison, WI, 53705, USA.

Achondroplasia is the most common of the skeletal dysplasias that result in marked short stature (dwarfism). Although its clinical and radiologic phenotype has been described for more than 50 years, there is still a great deal to be learned about the medical issues that arise secondary to this diagnosis, the manner in which these are best diagnosed and addressed, and whether preventive strategies can ameliorate the problems that can compromise the health and well being of affected individuals. This review provides both an updated discussion of the care needs of those with achondroplasia and an exploration of the limits of evidence that is available regarding care recommendations, controversies that are currently present, and the many areas of ignorance that remain. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318916PMC
January 2019
2 Reads

Is sleep apnea underdiagnosed in adult patients with osteogenesis imperfecta? -a single-center cross-sectional study.

Orphanet J Rare Dis 2018 Dec 29;13(1):231. Epub 2018 Dec 29.

Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Patients with Osteogenesis imperfecta (OI) suffer from increased bone fracture tendency generally caused by a mutation in genes coding for type I collagen. OI is also characterized by numerous co-morbidities, and recent data from questionnaire studies suggest that these may include increased risk for sleep apnea, a finding that lacks clinical evidence from cohort studies. In this cross-sectional study, 25 adults with OI underwent clinical otorhinolaryngology examination as well as overnight polysomnography to address the question. Read More

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http://dx.doi.org/10.1186/s13023-018-0971-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310950PMC
December 2018
2 Reads

X-linked Alport syndrome: pathogenic variant features and further auditory genotype-phenotype correlations in males.

Orphanet J Rare Dis 2018 Dec 22;13(1):229. Epub 2018 Dec 22.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.

Objective: To analyze the clinical audiological characteristics of X-Linked Alport syndrome (XLAS) in males and their relationships with genotypes.

Methods: The clinical data of 87 male patients with AS were reviewed. Hearing levels were evaluated using pure tone audiometry (PTA) testing, acoustic immittance, and otoacoustic emissions (OAE) testing. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0974-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303895PMC
December 2018
12 Reads

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism.

Orphanet J Rare Dis 2018 Dec 22;13(1):230. Epub 2018 Dec 22.

Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Read More

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http://dx.doi.org/10.1186/s13023-018-0970-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304089PMC
December 2018
2 Reads

Illustration of patient-reported outcome challenges and solutions in rare diseases: a systematic review in Cushing's syndrome.

Orphanet J Rare Dis 2018 Dec 19;13(1):228. Epub 2018 Dec 19.

Mapi, an ICON plc Company, 27 rue de la Villette, 69003, Lyon, France.

Rare diseases are often not fully understood and efforts put in investigating it from patient perspective are usually met with challenges. We performed a systematic literature review (SLR) for the last 20 years in Cushing's Syndrome (CS) to illustrate Patient-Reported Outcome (PRO) challenges, and show what solutions were found.PROs and other Clinical Outcome Assessment (COA) used with CS patients were reviewed in 36 studies. Read More

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http://dx.doi.org/10.1186/s13023-018-0958-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299940PMC
December 2018

Evaluation of DSD training schools organized by cost action BM1303 "DSDnet".

Orphanet J Rare Dis 2018 Dec 18;13(1):227. Epub 2018 Dec 18.

Division of Paediatric Endocrinology and Diabetes, University of Lübeck, Lübeck, Germany.

Background: The Differences of Sex Development network (DSDnet) aims to establish interactive relationships between clinicians, scientists, support groups and people with a difference of sex development (DSD) to improve the overall care for people affected by such condition. DSDnet has hosted three Training Schools (TSs) in Ghent, Bologna and Budapest between 2015 and 2017 with the primary purpose of providing multidisciplinary training to young professionals and encouraging ongoing activity in the field of DSD. The aim of our study was to evaluate the success and long-term effect effectiveness of these three TSs. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0967-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299629PMC
December 2018
4 Reads