The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype

BACKGROUND: The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive deterioration with a rapidly or slowly progressing phenotype. The presented MPS III case series demonstrates adult onset phenotypes with mild cognitive impairment or non-neuronopathic phenotypes. METHODS: In this case series all adult MPS III patients with a mild- or non-neuronopathic phenotype, who attend the outpatient clinic of 3 expert centers for lysosomal storage disorders were included. A mild- or non-neuronopathic phenotype was defined as having completed regular secondary education and attaining a level of independency during adulthood, involving either independent living or a paid job. RESULTS: Twelve patients from six families, with a median age at diagnosis of 43 years (range 3-68) were included (11 MPS IIIA, 1 MPS IIIB). In the four index patients symptoms which led to diagnostic studies (whole exome sequencing and metabolomics) resulting in the diagnosis of MPS III; two patients presented with retinal dystrophy, one with hypertrophic cardiomyopathy and one with neurocognitive decline. The other eight patients were diagnosed by family screening. At a median age of 47 years (range 19-74) 9 out of the 12 patients had normal cognitive functions. Nine patients had retinal dystrophy and 8 patients hypertrophic cardiomyopathy. CONCLUSION: We show the very mild end of the phenotypic spectrum of MPS III, ranging from late-onset stable neurocognitive impairment to a fully non-neuronopathic phenotype. Awareness of this phenotype could lead to timely diagnosis and genetic counseling

Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Analysis of selected chemical parameters in Piemontese wines

Background. Piemontese wines are well known and valued all over the world. The most popular of them are Barolo and Barbaresco wines. However, in Poland, they are still little known and only now are being gradually introduced to a wider range of consumers. Objective. The aim of this study was to evaluate the content of inorganic anions, minerals, sugars and glycerol of Piemontese wines from micro-region Langhe, classified as DOCG („Denominazione di Origine Controllata e Garantita”, ie. controlled designation of origin guaranteed) and DOC („Denominazione di Origine Controllata”, ie. controlled designation of origin) products. Material and Methods. Seven types of red wines and one type of white wine were tested. High Performance Ion Chromatography with conductometric detection (HPLC-CD) was used to measure the content of inorganic anions, ie. fluorides, chlorides, sulfates and phosphates. Flame atomic absorption spectrometry (F-AAS) was used to measure the content of minerals, ie. magnesium, calcium, sodium, copper, potassium, zinc and iron, while High Performance Liquid Chromatography with charged aerosol detection (HPLC-CAD) was used to measure the content of glycerol and sugars, ie. fructose, glucose and sucrose. Results. Our studies show that although Piemontese wines are characterized by a relatively low content of minerals in comparison with the wines from other regions, they contain a lot of ingredients that have beneficial effects for human health. Moreover, we observed that the studied wines contain particularly high concentration of inorganic ions – phosphates and fluorides. Furthermore, all tested red wines show far reaching similarities in their chemical properties, which is possibly a direct consequence of using in their production locally cultivated grape varieties. Conclusions. Analysis of the wines from the Piemont region, classified as DOCG, DOC, confirmed that these are dry wines of a high quality.Wprowadzenie. Wina piemonckie są znane i cenione na całym świecie. Wśród najpopularniejszych wymienia się wina Barolo i Barbaresco. W Polsce wina piemonckie są nadal mało znane i wprowadzane dopiero do dystrybucji. Cel. Celem badań była ocena zawartości anionów nieorganicznych, składników mineralnych oraz cukrów i glicerolu w winach piemonckich, klasyfikowanych jako wina DOCG („Denominazione di Origine Controllata e Garantita”, tj. o kontrolowanym oznaczeniu gwarantowanego pochodzenia) i DOC („Denominazione di Origine Controllata”, tj. o kontrolowanym oznaczeniu pochodzenia) z mikroregionu Langhe. Materiał i metody. W siedmiu czerwonych i jednym białym piemonckich winach oznaczano zawartość: składników mineralnych, tj. magnezu, wapnia, sodu, miedzi, potasu, cynku i żelaza z użyciem metody absorpcyjnej spektrometrii atomowej (ASA), anionów nieorganicznych, tj. fluorków, chlorków, siarczanów (VI) i fosforanów (V) z użyciem metody wysokosprawnej chromatografii jonowej z detekcją konduktometryczną (HPIC-CD) oraz glicerolu i cukrów, tj. fruktozy, glukozy i sacharozy z użyciem metody wysokosprawnej chromatografii cieczowej z detekcją wyładowań koronowych (HPLC-CAD). Wyniki: Badania wykazały, że wina piemonckie mogą być korzystnym źródłem składników prozdrowotnych, choć w porównaniu z innymi winami z całego świata charakteryzują się niską zawartością składników mineralnych. Wykazują także specyfikę pod względem wysokiej zawartości anionów nieorganicznych, tj. fluorków i fosforanów. Odnotowano równocześnie duże podobieństwa w składzie chemicznym win czerwonych, co może być charakterystyczne dla danego rejonu upraw winorośli. Wnioski. Analiza win piemonckich, klasyfikowanych jako DOCG i DOC potwierdziła, że są to wina wysokojakościowe i wytrawne

Transition of patients with mucopolysaccharidosis from paediatric to adult care

Mucopolysaccharidoses (MPS) are rare disorders associated with enzyme deficiencies, resulting in glycosaminoglycan (GAG) accumulation in multiple organ systems. As patients increasingly survive to adulthood, the need for a smooth transition into adult care is essential. Using case studies, we outline strategies and highlight the challenges of transition, illustrating practical solutions that may be used to optimise the transition process for patients with MPS disorders. Seven MPS case studies were provided by four European inherited metabolic disease centres; six of these patients transferred to an adult care setting and the final patient remained under paediatric care. Of the patients who transferred, age at the start of transition ranged between 14 and 18 years (age at transfer ranged from 16 to 19 years). While there were some shared features of transition strategies, they varied in duration, the healthcare professionals involved and the management of adult patients with MPS. Challenges included complex symptoms, patients' unwillingness to attend appointments with unfamiliar team members and attachment to paediatricians. Challenges were resolved by starting transition at an early age, educating patients and families, and providing regular communication with and reassurance to the patient and family. Sufficient time should be provided to allow patients to understand their responsibilities in the adult care setting while feeling assured of continued support from healthcare professionals. The involvement of a coordinated multidisciplinary team with expertise in MPS is also key. Overall, transition strategies must be comprehensive and individualised to patients' needs.Appendix A. Supplementary dataBioMarin Europe Ltd.http://www.elsevier.com/locate/ymgmram2020Industrial and Systems Engineerin