Classic galactosemia is an autosomal recessive disorder caused by deficient galactose-1-phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long-term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of GALT gene that characterizes this disorder is thought to play a determinant role in biochemical and clinical phenotypes. We aimed to characterize the mutational spectrum of GALT deficiency in Portugal and to assess potential genotype-phenotype correlations. Direct sequencing of the GALT gene and in silico analyses were employed to evaluate the impact of uncharacterized mutations upon GALT functionality. Molecular characterization of 42 galactosemic Portuguese patients revealed a mutational spectrum comprising 14 nucleotide substitutions: ten missense, two nonsense and two putative splicing mutations. Sixteen different genotypic combinations were detected, half of the patients being p.Q188R homozygotes. Notably, the second most frequent variation is a splicing mutation. In silico predictions complemented by a close-up on the mutations in the protein structure suggest that uncharacterized missense mutations have cumulative point effects on protein stability, oligomeric state, or substrate binding. One splicing mutation is predicted to cause an alternative splicing event. This study reinforces the difficulty in establishing a genotype-phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this "cloudy" disorder.

IntroductionHealthcare workers account for 10% of the EU’s total workforce, with a significant proportion of those employed in hospitals. Musculoskeletal injuries are the predominant group of injuries in healthcare professionals due to the physical demands of their work, such as the mobilization and positioning of the dependent patients. The management of this type of problem should take into account direct and indirect costs, such as periods of incapacity for work due to illness, hiring and training of new employees during periods of absence, reduced levels of productivity and the effects on production and quality of work.Objectives1—Characterization of injuries resulting from occupational accidents in hospital workers according to the International Classification of Diseases ICD-10; 2—Identification of the predictive factors of absenteeism duration due to temporary work incapacity in workplace accidents.MethodsA retrospective observational study was conducted based on the analysis of 1621 cases of work-related accidents of employees of Centro Hospitalar São João from January 2011 to December 2014.An ICD-10 classification code was associated with each of the accident cases, based on pre-established criteria for classification of the specific diagnoses of musculoskeletal injuries. The duration of temporary work incapacity was compared between the categories of sociodemographic variables, among six categories of ICD-10 primary diagnosis (reclassification), and between the two major chapters of ICD-10 classification—chapter XIX (direct trauma) and chapter XIII (indirect trauma—strain injuries). The sociodemographic predictors of the occurrence of strain injuries were determined by logistic regression. A multinomial logistic regression analysis was conducted with selection of duration of work incapacity as the dependent variable.ResultsA total of 824 cases of musculoskeletal injuries occurred on hospital premises during the study period, which corresponded to a total of 22159 lost workdays in the context of temporary work incapacity due to work injury. According to the ICD-10 reclassification, the three most frequent diagnostic groups were direct lower limb trauma (n = 230, 27.9%), spinal strain injuries (n = 194, 23.5%) and direct upper limb trauma (n = 174, 21.1%). Significant differences were observed in temporary work incapacity duration among the ICD-10 diagnostic categories: spinal strain injuries were the diagnostic group associated with longer duration of temporary work incapacity, with a median = 14.0 (25-75th percentile: 6.0–35.0). The only variable that demonstrated to be significantly predictive of temporary work incapacity less than or greater than 20 days was the ICD-10 diagnostic group. The regression results revealed a 5-fold increase in risk in the case of spinal strain injuries for temporary work incapacity durations of less than or greater than 20 days (OR = 5.58 and OR = 5.89 respectively).ConclusionsThe study findings support the benefits of the characterization of workplace injuries by medical d...