Orphanet Journal of Rare Diseases

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates...

BACKGROUND: The Ehlers-Danlos syndromes are a group of clinically and genetically heterogeneous hereditary diseases affecting the connective tissue. They are characterized by hypermobility of the joints, hyperextensible skin and friable tissue. According to current classification, 13 subtypes can be distinguished, of which the hypermobile and the classical subtype are the most prevalent. This study aimed to evaluate patients with classical (cEDS) and hypermobile (hEDS) Ehlers-Danlos syndrome regarding temporomandibular disorder (TMD), chronic pain, and psychological distress...

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan...

OBJECTIVE: To obtain updated estimates of the incidence and prevalence of neurofibromatosis type 1 (NF1) and type 2 (NF2). STUDY DESIGN: We conducted a systematic search of NF1 and NF2 incidence or prevalence studies, in OVID Medline, OVID Embase, Web of Science, and Cinahl. Studies were appraised with the Joanna Briggs Institute Prevalence Critical Appraisal tool. Pooled incidence and prevalence rates were estimated through random-effects meta-analysis. RESULTS: From 1,939 abstracts, 20 studies were fully appraised and 12 were included in the final review...

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients...

BACKGROUND: An association between punctate palmoplantar keratoderma type 1 (PPPK1) and malignancy has been proposed for decades. Some authors suggest that individuals with PPPK1 should undergo screening for various types of malignancies while others caution that an association is not well-established. In this systematic review, we summarized and evaluated the current evidence for a possible association between PPPK1 and malignancy. METHODS: The review was conducted along PRISMA guidelines...

BACKGROUND: Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM. METHODS: We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data...

Klippel-Trénaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. Gastrointestinal involvement is not infrequent in Klippel-Trénaunay syndrome. Rectal bleeding is the most common complication. In recent years, this condition has been increasingly reported. However, most authors simply described extreme manifestations or various combinations of clinical observations. The underlying pathophysiology of gastrointestinal involvement in Klippel-Trénaunay syndrome has been underrecognized...

BACKGROUND: The Covid pandemic seems to have had several detrimental effects on managing patients affected by inherited metabolic diseases (IMD), although published data about the impact of COVID-19 on patients suffering from IMD are very scarce. The scope of our work was to evaluate adherence to the vaccination plan, the side effects experienced by our adult IMD patients, and the symptoms of the SARS-CoV-2 infection. RESULTS: Sixty-seven patients agreed to respond to a phone interview...

BACKGROUND: We consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences-a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules-throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases...

BACKGROUND: Cardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants. RESULTS: Twenty Chinese CFC patients, aged 0.6-9.5 years old, were included in this study and their clinical phenotypic spectrum was compared with that of 186 patients with CFC from non-Chinese ethnicities...

BACKGROUND: Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS)...

BACKGROUND: Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging...

Necessity driven organisational change in the post-pandemic landscape has seen health care providers adopting innovations to manage and process health data. These include the use of 'real-world' datasets of routinely collected clinical information, enabling data-driven delivery. Rare disease risks being 'left-behind' unless our clinical and research communities engage with the challenges and opportunities afforded by the burgeoning field of health data informatics. We address the challenges to the meaningful use and reuse of rare disease data, and, through a series of recommendations around workforce education, harmonisation of taxonomy, and ensuring an inclusive health data environment, we highlight the role that those who manage rare disease must play in addressing them...

BACKGROUND: Early diagnosis of Gaucher disease (GD) allows for disease-specific treatment before significant symptoms arise, preventing/delaying onset of complications. Yet, many endure years-long diagnostic odysseys. We report the development of a machine learning algorithm to identify patients with GD from electronic health records. METHODS: We utilized Optum's de-identified Integrated Claims-Clinical dataset (2007-2019) for feature engineering and algorithm training/testing, based on clinical characteristics of GD...

Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. Early-onset PA can lead to acute deterioration, metabolic acidosis, and hyperammonemia shortly after birth, which can result in high mortality and disability. Late-onset cases of PA have a more heterogeneous clinical spectra, including growth retardation, intellectual disability, seizures, basal ganglia lesions, pancreatitis, cardiomyopathy, arrhythmias, adaptive immune defects, rhabdomyolysis, optic atrophy, hearing loss, premature ovarian failure, and chronic kidney disease...

BACKGROUND: Skeletal dysplasias are a diverse group of rare disorders in the chondro-osseous tissue that can have a significant impact on patient's functionality. The worldwide prevalence of skeletal dysplasias at birth is approximately 1:5000 births. To date, disease burden and trends of skeletal dysplasias in the Sri Lankan population have not been described in any epidemiological study. Our aim was to evaluate the burden and the current trends in hospital admissions for skeletal dysplasias in the Sri Lankan population...

OBJECTIVE: This study aimed to establish a cell-free fetal DNA (cffDNA) assay using multiplex digital PCR (dPCR) for identifying fetuses at increased risk of 22q11.2 deletion/duplication syndrome. METHODS: Six detection sites and their corresponding probes were designed for the 22q11.2 recurrent region. A dPCR assay for the noninvasive screening of 22q11.2 deletion/duplication syndrome was established. A total of 130 plasma samples from pregnant women (including 15 samples with fetal 22q11...

BACKGROUND: Childhood dementias are a group of rare and ultra-rare paediatric conditions clinically characterised by enduring global decline in central nervous system function, associated with a progressive loss of developmentally acquired skills, quality of life and shortened life expectancy. Traditional research, service development and advocacy efforts have been fragmented due to a focus on individual disorders, or groups classified by specific mechanisms or molecular pathogenesis...

INTRODUCTION: Sarcoidosis is a multisystemic disease, with the lungs being the main site of manifestation. Although the exact etiology remains unclear, both genetic and environmental factors are being discussed. Diagnostic evaluation is challenging, and the management of chronic patients and assessment of their needs proves difficult, especially in the absence of targeted therapy. Studies on sarcoidosis patients have shown that quality of life is limited even after clinically measurable parameters have resolved...