Articles

The TAND checklist: a useful screening tool in children with tuberous sclerosis and neurofibromatosis type 1

Tuberous Sclerosis Complex (TSC) and Neurofibromatosis type 1 (NF1) are neurocutaneous disorders commonly characterized by neuropsychiatric comorbidities. The TAND (Tuberous Sclerosis Associated Neuropsychiatr...

Authors: Francesca Cervi, Veronica Saletti, Katherine Turner, Angela Peron, Sara Bulgheroni, Matilde Taddei, Francesca La Briola, Maria Paola Canevini and Aglaia Vignoli

Bone mineral density and bone microarchitecture in a cohort of patients with Erdheim-Chester Disease

Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans histiocytosis. Skeletal structures are affected in over 95% ECD patients. Due to the lack of proper imaging assessment tools, the alteration of bo...

Authors: Tianhua He, Lijia Cui, Na Niu, Fengdan Wang, Huilei Miao, Hao Zhao, Xuemin Gao, Chang Liu, Fan Yu, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Daobin Zhou, Jian Li, Xinxin Cao…

Registries for orphan drugs: generating evidence or marketing tools?

Independent disease registries for pre-and post-approval of novel treatments for rare diseases are increasingly important for healthcare professionals, patients, regulators and the pharmaceutical industry. Cur...

Authors: Carla E. M. Hollak, Sandra Sirrs, Sibren van den Berg, Vincent van der Wel, Mirjam Langeveld, Hanka Dekker, Robin Lachmann and Saco J. de Visser

FDA orphan products clinical trial grants: assessment of outcomes and impact on rare disease product development

The Office of Orphan Products Development (OOPD) of the United States (U.S.) Food and Drug Administration (FDA) has awarded over 700 grants to conduct clinical trials of medicals products for rare diseases sin...

Authors: Kathleen L. Miller, Christine Mueller, Gumei Liu, Katherine I. Miller Needleman and Janet Maynard

Variability and change over time of weight and BMI among adolescents and adults with Prader-Willi syndrome: a 6-month text-based observational study

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for...

Authors: Caroline J. Vrana-Diaz, Priya Balasubramanian, Nathalie Kayadjanian, Jessica Bohonowych and Theresa V. Strong

Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study

Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease.

Authors: Meng Yuan, Eleni-Rosalina Andrinopoulou, Michelle E. Kruijshaar, Aglina Lika, Laurike Harlaar, Ans T. van der Ploeg, Dimitris Rizopoulos and Nadine A. M. E. van der Beek

Alternating Hemiplegia of Childhood: gastrointestinal manifestations and correlation with neurological impairments

Alternating Hemiplegia of Childhood (AHC) is caused by mutations of the ATP1A3 gene which is expressed in brain areas that include structures controling autonomic, gastrointestinal, gut motility and GABAergic ...

Authors: Milton Pratt, Julie Uchitel, Nancy McGreal, Kelly Gordon, Lyndsey Prange, Melissa McLean, Richard J. Noel, Blaire Rikard, Mary K. Rogers Boruta and Mohamad A. Mikati

Correction to: PKU dietary handbook to accompany PKU guidelines

An amendment to this paper has been published and can be accessed via the original article.

Authors: A. MacDonald, A. M. J. van Wegberg, K. Ahring, S. Beblo, A. Bélanger-Quintana, A. Burlina, J. Campistol, T. Coşkun, F. Feillet, M. Giżewska, S. C. Huijbregts, V. Leuzzi, F. Maillot, A. C. Muntau, J. C. Rocha, C. Romani…

Clinical profiles and risk factors of 7-day and 30-day mortality among 160 pediatric patients with hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and...

Authors: Xun Li, Haipeng Yan, Xinping Zhang, Jiaotian Huang, Shi-Ting Xiang, Zhenya Yao, Ping Zang, Desheng Zhu, Zhenghui Xiao and Xiulan Lu

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the “COVID-19 Helpline for Rare B...

Authors: E. Brizola, G. Adami, G. I. Baroncelli, M. F. Bedeschi, P. Berardi, S. Boero, M. L. Brandi, L. Casareto, E. Castagnola, P. Fraschini, D. Gatti, S. Giannini, M. V. Gonfiantini, V. Landoni, A. Magrelli, G. Mantovani…

Multi-level consistent changes of the ECM pathway identified in a typical keratoconus twin’s family by multi-omics analysis

Keratoconus (KC) is a common, degenerative disorder of the cornea, and genetic factors play a key role in its development. However, the genetic etiology of KC is still unclear. This study used the family of tw...

Authors: Xiao-dan Hao, Xiu-nian Chen, Yang-yang Zhang, Peng Chen, Chao Wei, Wei-yun Shi and Hua Gao

Participation in patient support forums may put rare disease patient data at risk of re-identification

Rare disease patients often struggle to find both medical advice and emotional support for their diagnosis. Consequently, many rare disease patient support forums have appeared on hospital webpages, social med...

Authors: James Gow, Colin Moffatt and Jamie Blackport

Immune-mediated thrombotic thrombocytopenic purpura in patients with and without systemic lupus erythematosus: a retrospective study

Thrombotic thrombocytopenic purpura (TTP) is associated with more deleterious outcomes in patients with systemic lupus erythematosus (SLE). However, ADAMTS13 (a disintegrin and metalloproteinase with a thrombo...

Authors: Cai Yue, Jian Su, Xiaohong Fan, Li Song, Wei Jiang, Jinghua Xia, Tao Shi, Xuan Zhang and Xuemei Li

Impact of the therapeutic positioning report in the P&R process in Spain: analysis of orphan drugs approved by the European Commission and reimbursed in Spain from 2003 to 2019

Pricing and reimbursement decisions for orphan drugs are faced with differences access between European countries depending on each reimbursement policies, evaluation processes and timings. In 2013, the therap...

Authors: Xavier Badia, Tania Vico, John Shepherd, Alicia Gil, José Luis Poveda-Andrés and César Hernández

Early management of sight threatening retinopathy in incontinentia pigmenti

Early blindness secondary to incurable retinal detachment is one of the main complications of incontinentia pigmenti (IP). The efficiency of ophthalmological management for preventing such evolution has not been ...

Authors: Sarah Michel, Clothilde Reynaud, Alejandra Daruich, Smail Hadj-Rabia, Dominique Bremond-Gignac, Christine Bodemer and Matthieu P. Robert

Variant c.2158-2A>G in MANBA is an important and frequent cause of hereditary hearing loss and beta-mannosidosis among the Czech and Slovak Roma population- evidence for a new ethnic-specific variant

The Roma are a European ethnic minority threatened by several recessive diseases.

Authors: Dana Safka Brozkova, Lukas Varga, Anna Uhrova Meszarosova, Zuzana Slobodova, Martina Skopkova, Andrea Soltysova, Andrej Ficek, Jan Jencik, Jana Lastuvkova, Daniela Gasperikova and Pavel Seeman

A Germany-wide survey study on the patient journey of patients with hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disease and characterized by clinical features such as paroxysmal, recurrent angioedema of the skin, the gastrointestinal tract, and the upper airways. Swelling of...

Authors: Markus Magerl, Holger Gothe, Simon Krupka, Anja Lachmann and Christoph Ohlmeier

Fabry disease screening in high-risk populations in Japan: a nationwide study

Fabry disease (FD) is a X-linked inherited disorder caused by mutations in the GLA gene, which results in the deficiency of α-galactosidase A (α-Gal A). This leads to the progressive accumulation of metabolites, ...

Authors: Shinichiro Yoshida, Jun Kido, Takaaki Sawada, Ken Momosaki, Keishin Sugawara, Shirou Matsumoto, Fumio Endo and Kimitoshi Nakamura

European principles of inhibitor management in patients with haemophilia: implications of new treatment options

Authors: C. Hermans, P. L. F. Giangrande, B. O’Mahony, P. de Kleijn, M. Bedford, A. Batorova, J. Blatný and K. Jansone

Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib

Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropen...

Authors: Sarah C. Grünert, Roland Elling, Bärbel Maag, Saskia B. Wortmann, Terry G. J. Derks, Luciana Hannibal, Anke Schumann, Stefanie Rosenbaum-Fabian and Ute Spiekerkoetter

Quality of life data for individuals affected by spinal muscular atrophy: a baseline dataset from the Cure SMA Community Update Survey

Individuals and/or caregivers of individuals affected by spinal muscular atrophy (SMA) completed the 2019 Cure SMA Community Update Survey, online, assessing health-related quality of life (HRQoL), loss of wor...

Authors: Lisa Belter, Rosángel Cruz and Jill Jarecki

Screening for Fabry disease in unknown origin axonal polyneuropathy: to do or not to do, this is the question!

Fabry disease (FD) is a systemic X-linked lysosomal disorder. A ‘peripheral nerve variant’ of FD has been hypothesized in subjects with neuropathy, without the early manifestations of the classic phenotype. A ...

Authors: Eugenia Rota, Marina Grandis, Alessia Di Sapio, Elisabetta Ghiglione, Pietro Fiorentino, Alessandra Repetto, Claudia Giliberto, Chiara Gemelli, Nicola Morelli, Angelo Schenone and Dario Cocito

A novel prognostic model for adult patients with Hemophagocytic Lymphohistiocytosis

Hemophagocytic Lymphohistiocytosis (HLH) is a type of rare disease with low survival rate. We aimed to develop a model to evaluate the six-month prognosis in adult HLH patients. The data at discharge (will be ...

Authors: Jun Zhou, Jing Zhou, Zhi-Qi Wu, Hemant Goyal and Hua-Guo Xu

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal second...

Authors: Morten Krogh Herlin, Michael Bjørn Petersen and Mats Brännström

Increased phototoxic burn tolerance time and quality of life in patients with erythropoietic protoporphyria treated with afamelanotide – a three years observational study

Erythropoietic protoporphyria (EPP) is an ultra-rare genetic disorder (prevalence 1:150`000) characterized by instant painful phototoxic burn reactions in skin exposed to visible light. Afamelanotide is the fi...

Authors: Jasmin Barman-Aksözen, Michèle Nydegger, Xiaoye Schneider-Yin and Anna-Elisabeth Minder

Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children

Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical pres...

Authors: Marius Vogt, Hermann Girschick, Tilmann Schweitzer, Clemens Benoit, Annette Holl-Wieden, Lothar Seefried, Franz Jakob and Christine Hofmann

Synergistic apoptosis following endoplasmic reticulum stress aggravation in mucinous colon cancer

Mucinous colon cancers (MCC) are characterized by abundant production of mucin 2 (MUC2) protein and are less sensitive to standard systemic chemotherapy. We postulated that severe/persistent endoplasmic reticu...

Authors: Ashok K. Dilly, Brendon D. Honick, Yong J. Lee, David L. Bartlett and Haroon A. Choudry

Clouds over IMD? Perspectives for inherited metabolic diseases in adults from a retrospective cohort study in two Swiss adult metabolic clinics

Inherited metabolic diseases (IMD) are complex medical conditions. Thanks to improvements in diagnosis and treatment, a growing number of pediatric IMD patients reach adulthood. Thus, clinical care of adults w...

Authors: Karim Gariani, Marina Nascimento, Andrea Superti-Furga and Christel Tran

Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a genetic disorder that cause tumors to form in many organs. These lesions may lead to epilepsy, autism, developmental delay, renal, and pulmonary failure. Loss of function ...

Authors: Yiyang Lu, Erik Y. Zhang, Jie Liu and Jane J. Yu

Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction

Peutz-Jeghers Syndrome (PJS) is known as a rare inherited polyposis due to the malfunction of serine/threonine kinase gene LKB1. However, not all of PJS patients carry LKB1 germline mutation. Previous researches ...

Authors: Teng Li, Wensheng Lin, Yilei Zhao, Jianping Zhu, Tao Sun and Li Ren

Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis

Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract–microcornea syndromes.

Authors: Andrey V. Marakhonov, Anna A. Voskresenskaya, Maria Jose Ballesta, Fedor A. Konovalov, Tatyana A. Vasilyeva, Fiona Blanco-Kelly, Nadezhda A. Pozdeyeva, Vitaly V. Kadyshev, Vanesa López-González, Encarna Guillen, Carmen Ayuso, Rena A. Zinchenko and Marta Corton

A guide to writing systematic reviews of rare disease treatments to generate FAIR-compliant datasets: building a Treatabolome

Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients ...

Authors: Antonio Atalaia, Rachel Thompson, Alberto Corvo, Leigh Carmody, Davide Piscia, Leslie Matalonga, Alfons Macaya, Angela Lochmuller, Bertrand Fontaine, Birte Zurek, Carles Hernandez-Ferrer, Carola Rheinard, David Gómez-Andrés, Jean-François Desaphy, Katherine Schon, Katja Lohmann…

Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) belongs to a group of conditions called the PIK3CA-related overgrowth spectrum (PROS). The varying phenotypes and low frequencies of each somat...

Authors: Hyun Jin Park, Chang Ho Shin, Won Joon Yoo, Tae-Joon Cho, Man Jin Kim, Moon-Woo Seong, Sung Sup Park, Jeong Ho Lee, Nam Suk Sim and Jung Min Ko

Characterization of tracheobronchomalacia in infants with hypophosphatasia

Perinatal and infantile hypophosphatasia (HPP) are associated with respiratory failure and respiratory complications. Effective management of such complications is of key clinical importance. In some infants w...

Authors: Raja Padidela, Robert Yates, Dan Benscoter, Gary McPhail, Elaine Chan, Jaya Nichani, M. Zulf Mughal, Charles Myer IV, Omendra Narayan, Claire Nissenbaum, Stuart Wilkinson, Shanggen Zhou and Howard M. Saal

Cyclin-dependent kinases and rare developmental disorders

Extensive studies in the past 30 years have established that cyclin-dependent kinases (CDKs) exert many diverse, important functions in a number of molecular and cellular processes that are at play during deve...

Authors: Pierre Colas

Correction to: Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

An amendment to this paper has been published and can be accessed via the original article.

Authors: Thomas Opladen, Eduardo López-Laso, Elisenda Cortès-Saladelafont, Toni S. Pearson, H. Serap Sivri, Yilmaz Yildiz, Birgit Assmann, Manju A. Kurian, Vincenzo Leuzzi, Simon Heales, Simon Pope, Francesco Porta, Angeles García-Cazorla, Tomáš Honzík, Roser Pons, Luc Regal…

Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence)

Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast,...

Authors: Ilaria Baldelli, Alessio Baccarani, Chiara Barone, Francesca Bedeschi, Sebastiano Bianca, Olga Calabrese, Marco Castori, Nunzio Catena, Massimo Corain, Sara Costanzo, Giacomo De Paoli Barbato, Santa De Stefano, Maria Teresa Divizia, Francesco Feletti, Matteo Formica, Mario Lando…

PKU dietary handbook to accompany PKU guidelines

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine.

Authors: A. MacDonald, A. M. J. van Wegberg, K. Ahring, S. Beblo, A. Bélanger-Quintana, A. Burlina, J. Campistol, T. Coşkun, F. Feillet, M. Giżewska, S. C. Huijbregts, V. Leuzzi, F. Maillot, A. C. Muntau, J. C. Rocha, C. Romani…

Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases

Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients...

Authors: Ruxuan He, Ruo Mo, Ming Shen, Lulu Kang, Jinqing Song, Yi Liu, Zhehui Chen, Hongwu Zhang, Hongxin Yao, Yupeng Liu, Yao Zhang, Hui Dong, Ying Jin, Mengqiu Li, Jiong Qin, Hong Zheng…

A feasibility study of mHealth and wearable technology in late onset GM2 gangliosidosis (Tay-Sachs and Sandhoff Disease)

As part of a late onset GM2 gangliosidosis natural history study, digital health technology was utilized to monitor a group of patients remotely between hospital visits. This approach was explored as a means o...

Authors: Elin Haf Davies, Jean Johnston, Camilo Toro and Cynthia J. Tifft

Onset features and time to diagnosis in Friedreich’s Ataxia

In rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich’s Ataxia (FRDA), a genetic disorder usuall...

Authors: Elisabetta Indelicato, Wolfgang Nachbauer, Andreas Eigentler, Matthias Amprosi, Raffaella Matteucci Gothe, Paola Giunti, Caterina Mariotti, Javier Arpa, Alexandra Durr, Thomas Klopstock, Ludger Schöls, Ilaria Giordano, Katrin Bürk, Massimo Pandolfo, Claire Didszdun, Jörg B. Schulz…

Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

The Ehlers-Danlos syndromes (EDS) are rare connective tissue disorders consisting of 13 subtypes with overlapping features including joint hypermobility, skin and generalized connective tissue fragility. Class...

Authors: Marco Ritelli, Marina Venturini, Valeria Cinquina, Nicola Chiarelli and Marina Colombi

Impact of cardiovascular involvement on the clinical course of paediatric mitochondrial disorders

Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related preva...

Authors: Alice Brambilla, Iacopo Olivotto, Silvia Favilli, Gaia Spaziani, Silvia Passantino, Elena Procopio, Amelia Morrone and Maria Alice Donati

The infantile neuroaxonal dystrophy rating scale (INAD-RS)

INAD is an autosomal recessive neurogenetic disorder caused by biallelic pathogenic variants in PLA2G6. The downstream enzyme, iPLA₂, plays a critical role in cell membrane homeostasis by helping to regulate leve...

Authors: Paldeep S. Atwal, Mark Midei, Darius Adams, Alexander Fay, Frederic Heerinckx and Peter Milner

Experiences of caregivers of children with spinal muscular atrophy participating in the expanded access program for nusinersen: a longitudinal qualitative study

Expanded access programs (EAPs) allow patients with serious, life-threatening conditions access to drugs prior to their formal approval. Despite the possible benefits for patients, EAPs present several challen...

Authors: Petra Kiefer, Janbernd Kirschner, Astrid Pechmann and Thorsten Langer

Patients with ACVR1^R206H mutations have an increased prevalence of cardiac conduction abnormalities on electrocardiogram in a natural history study of Fibrodysplasia Ossificans Progressiva

Genetic contributors to cardiac arrhythmias are often found in cardiovascular conduction pathways and ion channel proteins. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease of massive heter...

Authors: Samuel Kou, Carmen De Cunto, Geneviève Baujat, Kelly L. Wentworth, Donna R. Grogan, Matthew A. Brown, Maja Di Rocco, Richard Keen, Mona Al Mukaddam, Kim-Hanh le Quan Sang, Umesh Masharani, Frederick S. Kaplan, Robert J. Pignolo and Edward C. Hsiao

ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes

ETV6-ACSL6 is a fusion gene rarely reported in myeloid malignancies, and its clinical characteristics, proper treatment strategies, and effect on prognosis are poorly understood.

Authors: Xia Wu, Hao Cai, Yu Qiu, Jian Li, Dao-bin Zhou and Xin-xin Cao

Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: evaluation of outcomes after liver transplantation

Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver trans...

Authors: Masaru Shimura, Naomi Kuranobu, Minako Ogawa-Tominaga, Nana Akiyama, Yohei Sugiyama, Tomohiro Ebihara, Takuya Fushimi, Keiko Ichimoto, Ayako Matsunaga, Tomoko Tsuruoka, Yoshihito Kishita, Shuichiro Umetsu, Ayano Inui, Tomoo Fujisawa, Ken Tanikawa, Reiko Ito…

Clinician-centric diagnosis of rare genetic diseases: performance of a gene pertinence metric in decision support for clinicians

In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a ...

Authors: Michael M. Segal, Renee George, Peter Waltman, Ayman W. El-Hattab, Kiely N. James, Valentina Stanley and Joseph Gleeson

Wound closure in epidermolysis bullosa: data from the vehicle arm of the phase 3 ESSENCE Study

Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control...

Authors: Dedee F. Murrell, Amy S. Paller, Christine Bodemer, John Browning, Milos Nikolic, Jay A. Barth, Hjalmar Lagast, Eva Krusinska and Allen Reha