ABSTRACT
D-2-hydroxyglutaric aciduria type II (D2HGA2) is a severe inborn disorder of metabolism caused by heterozygous R140 mutations in the IDH2 (isocitrate dehydrogenase 2) gene. Here we report the results of treatment of two children with D2HGA2, one of whom exhibited severe dilated cardiomyopathy, with the selective mutant IDH2 enzyme inhibitor enasidenib. In both children, enasidenib treatment led to normalization of D-2-hydroxyglutarate (D-2-HG) concentrations in body fluids. At doses of 50 mg and 60 mg per day, no side effects were observed, except for asymptomatic hyperbilirubinemia. For the child with cardiomyopathy, chronic D-2-HG inhibition was associated with improved cardiac function, and for both children, therapy was associated with improved daily functioning, global motility and social interactions. Treatment of the child with cardiomyopathy led to therapy-coordinated changes in serum phospholipid levels, which were partly recapitulated in cultured fibroblasts, associated with complex effects on lipid and redox-related gene pathways. These findings indicate that targeted inhibition of a mutant enzyme can partly reverse the pathology of a chronic neurometabolic genetic disorder.
Subject(s)
Cardiomyopathies , Isocitrate Dehydrogenase , Child , Humans , Cardiomyopathies/drug therapy , Cardiomyopathies/genetics , Enzyme Inhibitors/adverse effects , Germ Cells/metabolism , Isocitrate Dehydrogenase/metabolism , Mutation/geneticsABSTRACT
INTRODUCTION: Attitudes and knowledge of health professionals are critical dimensions in the management of suicidal behavior. The "Suicide Behavioral Attitude Questionnaire" (SBAQ) was designed in Brazil to measure these variables in paramedical personnel. AIM: To translate and validate the SBAQ in literary Arabic. METHODS: After author-approved translation and back-translation, the Arabic version of the SBAQ was distributed to 125 Tunisian caregivers working in psychiatric departments. Factor analysis and internal consistency were calculated. The stability was measured overtime using the paired Student's T-test. RESULTS: Cronbach's alpha value was 0.741. The adequacy index of the factorization factor Kaiser-Meyer-Olkin (KMO) of our sample was 0.74. This value was higher than 0.5 which indicates that our data was suited for factor analysis. Bartlett's sphericity test result was significant, rejecting the null hypothesis. Three factors were extracted explaining 50.7% of the overall variance. Cronbach's alpha value for the three subscales was 0.735, 0.713 and 0.798. The instrument had good stability over time. CONCLUSIONS: The Arabic version of the SBAQ showed good reliability and validity allowing its use in Arabic speaking paramedical personnel.
