Krabbe disease: the importance of early diagnosis to prognosis / Doença de Krabbe: a importância do diagnóstico precoce para seu prognóstico

Krabbe disease (globoid cell leukodystrophy) is an inherited recessive autosomal leukodystrophy caused by deficiency of the enzyme galactocerebrosidase. The lack of this enzyme leads to the build-up of galactolipids that will promote the death of oligodendrocytes and the demyelination of the central and peripheral nervous systems. There are two clinical forms: early onset and late onset. This article reports a case of late onset Krabbe disease and discusses the importance of early diagnosis for its prognosis.

Doença de Krabbe (leucodistrofia de células globoides) é uma leucodistrofia de herança autossômica recessiva causada pela deficiência da enzima galactocerebrosidase. A falta dessa enzima leva ao acúmulo de galactolipídeos que irão promover a morte dos oligodendrócitos e a desmielinização do sistema nervoso central e periférico. Possui duas formas clínicas: de início precoce e de aparecimento tardio. O presente artigo relata um caso da apresentação tardia da doença de Krabbe e discute a importância do diagnóstico precoce para o seu prognóstico.

Confiabilidad y validez de la versión chilena de la Hare PCL-R / Chilean version of Hare PCL-R: a study of reliability and validity

Antecedentes. En Chile, al igual que en otros países latinoamericanos, diversas modificaciones judiciales y el interés de los profesionales en sistematizar sus métodos de evaluación en psicopatía promovieron la traducción, adaptación y revisión de las propiedades psicométricas de la Hare Psychopathy Checklist Revised (PCL-R). Objetivo. Evaluar aspectos de la confiabilidad y validez de la versión chilena del PCL-R en población forense masculina chilena. Material y métodos. Se realizó traducción y retrotraducción de la escala con la autorización del autor y editorial; se constituyó una muestra de 293 sujetos varones penados que aceptaron participar en la investigación. Entre otros análisis, se contrastó el diagnóstico obtenido a ciegas con la PCL-R con el aportado por el equipo técnico de Gendarmería de Chile. Resultados. La congruencia interna medida con Alfa de Cronbach fue la siguiente: total =0,91; F1= 0,86; F2 = 0,87; F3 = 0,67; F4= 0,77. Valor Kappa ambos tipos de evaluaciones = 0,804; p < 0,001. Se obtuvo significativa asociación entre condición psicópata y reincidente (OR = 12,8; 95 % IC = 5; 33). El análisis factorial confirmatorio resultó compatible con el modelo de cuatro factores. Conclusión. Los resultados orientan a sostener la validez de la versión chilena de la PCL-R y la solución de cuatro factores para el constructo de Psicopatía medido con el instrumento.

A Korean Case of Infantile Krabbe Disease with a Novel GALC Gene Mutation / 대한소아신경학회지

Krabbe disease is a rare autosomal recessive neurodegenerative disorder caused by mutations in the galactocerebrosidase(GALC) gene. The deficiency of GALC activity leads to the accumulation of psychosine, resulting in apoptosis of myelin-forming cells of the central and peripheral nervous system. The patients with typical infantile onset Krabbe disease have extreme irritability, developmental regression, spasticity, and seizures with an onset prior to six months of age. These children usually die within two years after birth. We report a female infant who showed the characteristic clinical manifestations, disease course, and neuroimaging features of infantile onset Krabbe disease that was confirmed by the identification of a compound heterozygous mutation of the GALC gene.

Effect of psychosine on mitochondrial function.

The effect of psychosine on the rate of respiration at different segments of the electron transport chain, respiratory control ratio and the efficiency of phosphorylation was studied. The transfer of electrons through site I, site II and site III was studied independently. The transfer through site I and site III was inhibited by psychosine, whereas the transfer through site II was not inhibited. Cardiolipin, which is essential for the electron transfer through site I and III, was implicated to be responsible for the inhibition of electron transfer by psychosine. Electron carriers of site II are not sensitive to cardiolipin, so psychosine could not inhibit the electron transfer through this site. The ADP/O ratio and respiratory control ratio were inhibited by psychosine showing that it has an uncoupler like effect. Mitochondria isolated from rat liver, kidney and brain behaved essentially the same way in their response to psychosine. Cytochrome c oxidase was significantly inhibited by psychosine and the degree of inhibition was almost same in mitochondria and sub mitochondrial particles. The preence of outer membrane in mitochondria did not make any difference with respect to the action of psychosine on electron transport chain. Psychosine interacts at site I and site III and a change in the lipid environment of the membrane is responsible for the mitochondrial dysfunctions induced by psychosine. This represents a possible mechanism for the destruction of cells in Gaucher's and Krabbe's disease.