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Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long-term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme-replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I., (© 2022 Wiley Periodicals LLC.)

Monitoring the proteins and lipids that mediate all cellular processes requires imaging methods with increased spatial and temporal resolution. STED (stimulated emission depletion) nanoscopy enables fast imaging of nanoscale structures in living cells but is limited by photobleaching. Here, we present event-triggered STED, an automated multiscale method capable of rapidly initiating two-dimensional (2D) and 3D STED imaging after detecting cellular events such as protein recruitment, vesicle trafficking and second messengers activity using biosensors. STED is applied in the vicinity of detected events to maximize the temporal resolution. We imaged synaptic vesicle dynamics at up to 24 Hz, 40 ms after local calcium activity; endocytosis and exocytosis events at up to 11 Hz, 40 ms after local protein recruitment or pH changes; and the interaction between endosomal vesicles at up to 3 Hz, 70 ms after approaching one another. Event-triggered STED extends the capabilities of live nanoscale imaging, enabling novel biological observations in real time., (© 2022. The Author(s).)

Background: Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is mainly associated with mutations in the EDA, EDAR, and EDARADD responsible for the development of ectodermal-derived structures. HED displays different modes of inheritance according to the gene that is involved, with X-linked EDA-related HED being the most frequent form of the disease., Methods: Two families with tooth agenesis and manifestations of HED underwent clinical examination and EDA, EDAR, and EDARADD genetic analysis. The impact of the novel variant on the protein was evaluated through bioinformatics tools, whereas molecular modeling was used to predict the effect on the protein structure., Results: A novel missense variant was identified in the EDAR (c.287T>C, p.Phe96Ser) of a female child proband and her mother, accounting for autosomal dominant HED. The genetic variant c.866G>A (p.Arg289His) in EDA, which has been previously described, was observed in the male proband of another family confirming its role in X-linked HED. The inheritance model of the missense mutation showed a different relationship with X-linked HED and non-syndromic tooth agenesis., Conclusion: Our findings provide evidence of variable expression of HED in heterozygous females, which should be considered for genetic counseling, and different modes of inheritance related to tooth development., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

BACKGROUND: Biliopancreatic Diversion (BPD), excluding the jejunum and part of the ileum from the transit of the food, reduces the absorptive intestinal area available to 250 cm of the distal ileum. The Intestinal Permeability Test (IPT) with Lactulose/Mannitol is performed to assess the intestinal mucosa function. The aim of this study was to investigate the effect of intestinal anatomical modifications induced by BPD on IPT in a group of severely obese patients. METHODS: Group A: 18 severely obese subjects who underwent BPD; the IPT was performed before (T0) and 8.2 +/- 0.9 days after BPD (T1). Group B: nine subjects of Group A; IPT was repeated 96.1 +/- 12.7 days (T2) and 180.4 +/- 19.7 days (T3) after BPD, respectively. IPT was expressed as the %Lactulose/%Mannitol ratio in the urine collected during 5 h after oral administration (normal %L/%M < 0.04). RESULTS: Data from Group A (paired Student's t-test) exhibited significantly higher values in T, with respect to T0 for %L/%M (p < 0.05) and for %L (p < 0.05), and significantly lower values in T, with respect to T0 (p < 0.001) for %M. In the Group B analysis of Variance from T0-T1-T2-T3 resulted statistically significant (p < 0.05) for % L/ % M and % M. CONCLUSIONS: The reduction of intestinal absorption surface induced by BPD causes a significant increase of the Lactulose/Mannitol IPT values, showing an intestinal mucosa function impairment. The IPT values improve progressively at 3 and 6 months after this surgical procedure.