This study provides longitudinal data of NSAA and 6MWT over a 12-month period. These data can be useful when designing a clinical trial.

Italy is the second exposed country worldwide, after China, and Lombardia is the most affected region in Italy, with more than half of the national cases, with 13% of whom being healthcare professionals. The Clinica Pediatrica Università degli Studi di Milano Bicocca is a general pediatric and hematology oncology and transplant center embedded within the designated COVID-19 general Hospital San Gerardo in Monza, located in Lombardia, Italy. Preventive and control measures specifically undertaken to cope with the emergency within hemato-oncology, transplant, and outpatient unit in the pediatric department have been described. Preliminary COVID-19 experiences with the first Italian pediatric hemato-oncology patients are reported. The few available data regarding pediatrics and specifically hemato-oncological patients are discussed. The purpose of this report is to share pediatric hemato-oncology issues encountered in the first few weeks of the COVID-19 outbreak in Italy and to alert healthcare professionals worldwide to be prepared accordingly. Background-the SARS-CoV-2 outbreak in ItalyAs of March 18, at 4 p.m., according to the WHO dashboard, updated every 15 min, 194,029 cases of SARS CoV-2 infection in 164 countries have been confirmed worldwide, yielding 7873 deaths [1].On the same date, the Istituto Superiore di Sanità (ISS) reported 31,506 cases in Italy, the second exposed country in the worldwide list, after China. Healthcare professionals constitute 9% of the confirmed case. Overall 2503 deaths have been reported in Italy. Cases are defined by positive molecular tests analyzed in specific regional laboratories, designated by the health authority. In the cases reported above, symptoms were absent in 6%, mild in 55%, unspecified in 10%, severe in 25%, life-threatening in 4%. Criteria for performing swabs varied overtime, with most symptomatic cases and contacts of confirmed cases being included in the first weeks and mainly severe cases being the majority of the tested cases more recently. 13% of the positive cases have been admitted in hospitals so far and 12% of them have been assisted in intensive care units (ICU) [2].Lombardia is, by far, the most affected region in Italy, with more than half of the national cases (median age 65 years, range 0-101), with 13% of whom being healthcare professionals. Most cases are concentrated in the Bergamo area [3].

GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000– 1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes, showed that all the amino acids replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease.

Common, clinical findings of SRD, aside from oculogyric crises and diurnal fluctuation, are nonspecific and mimic CP with hypotonia or dystonia. Patients usually improve dramatically with treatment. Consequently, we recommend consideration of SRD not only in patients with levodopa-responsive motor disorders, but also in patients with developmental delays with axial hypotonia, and patients with unexplained or atypical presumed CP. Biochemical investigation of cerebrospinal fluid is the preferred method of initial investigation. Early diagnosis and treatment are recommended to prevent ongoing brain dysfunction.