Orphanet J Rare Dis
-
Orphanet J Rare Dis · Jul 2020
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. Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants and rarely by the COL1A1 p.(Arg312Cys) substitution. Current major criteria are (1) skin hyperextensibility plus atrophic scars and (2) generalized joint hypermobility (gJHM). Minor criteria include additional mucocutaneous signs, epicanthal folds, gJHM complications, and an affected first-degree relative. Minimal criteria prompting molecular testing are major criterion 1 plus either major criterion 2 or 3 minor criteria. In addition to these features, the clinical picture also involves multiple organ systems, but large-scale cohort studies are still missing. This study aimed to investigate the multisystemic involvement and natural history of cEDS through a cross-sectional study on a cohort of 75 molecularly confirmed patients evaluated from 2010 to 2019 in a tertiary referral center. The diagnostic criteria, additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, and atopic issues, and facial/ocular features were ascertained, and feature rates compared by sex and age. ⋯ Our findings define the diagnostic relevance of cutaneous and articular features and additional clinical signs associated to cEDS. Furthermore, our data suggest an update of the current EDS nosology concerning scarring that should be considered separately from skin hyperextensibility and that the clinical diagnosis of cEDS may be enhanced by the accurate evaluation of orthopedic manifestations at all ages, faciocutaneous indicators in children, and some acquired traits related to joint instability complications, premature skin aging, and patterning of abnormal scarring in older individuals.
-
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. ⋯ This handbook can support dietitians, nutritionists and physicians in starting, adjusting and maintaining dietary treatment.
-
Orphanet J Rare Dis · May 2020
ReviewPreclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.
Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics. ⋯ Over the past 30 years, there were 262 publications on MH and RYR1-RM preclinical model systems featuring more than 200 unique RYR1 variations tested in a broad range of species. Findings from these studies have set the foundation for therapeutic development for MH and RYR1-RM.
-
Orphanet J Rare Dis · Mar 2020
Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis.
Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical syndrome with high mortality rate. The diagnosis of HLH draws on a constellation of clinical and laboratory abnormalities including extremely high serum ferritin levels. However, no biomarker has been firmly established as a clinically useful prognostic tool in HLH patients. We aimed to perform a retrospective analysis of two independent cohorts to explore the prognostic value of discharge serum ferritin for newly diagnosed adult HLH patients who recently started treatment. The prognostic value of serum ferritin levels at discharge (will be called as post-treatment ferritin level) was initially evaluated in a "test cohort" of 161 previously untreated consecutive adult HLH patients. It was then validated in a second cohort of 68 consecutive previously untreated patients (validation cohort). ⋯ These results suggest that the serum ferritin level can be used as an independent prognostic marker in the adult HLH patients.
-
Orphanet J Rare Dis · Jan 2020
Multicenter StudyManagement and current status of spinal muscular atrophy: a retrospective multicentre claims database analysis.
The interest in patient demographics and disease management has increased in the past years due to their utility in developing measures that allow healthcare providers to reflect disease complexity. ⋯ Patients exhibited similar characteristics to prior European studies. Multiple admissions in younger patients, mostly due to respiratory issues, have a central role in increasing medical costs of SMA. Equally, the higher risk of patients and increased number of multimorbidity groups translate in an elevated number of admissions in health centres and ER, deriving in higher expenses.