Krabbe disease: the importance of early diagnosis for prognosis

Abstract

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.Keywords: Leukodystrophy, globoid cell; Galactosylceramidase; Psychosine; Galactolipids; Early diagnosis; Case reports RESUMO 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.

Acute-onset paralytic strabismus in toddlers is important to consider as a potential early sign of late-infantile Metachromatic Leukodystrophy

“…With this study, we therefore emphasize that presentation of paralytic strabismus in toddlers younger than 2.5 years, especially when characterized by an acute onset esotropia or when accompanied by abnormal motor development or other eye movement disorders, could be an early or presenting clinical sign of MLD, even if brain white matter abnormalities are still absent. In addition, since acute-onset of strabismus has also been reported as an early sign in Krabbe disease, multiple sulfatase deficiency and mucolipidosis (7,21,(31)(32)(33)(34)(35) , we recommend immediate referral to a pediatric neurologist who should also consider lysosomal leukodystrophies.…”

A qualitative assessment of parental experiences with false‐positive newborn screening for Krabbe disease

“…Krabbe disease does not meet traditional NBS criteria, as differentiating infantile onset from late onset disease makes determining who to treat quite difficult and long‐term data to support HSCT as an accepted treatment is limited. Despite the fact that Krabbe disease fails to meet traditional NBS criteria, and against the recommendation of the American College of Medical Genetics (Duffner et al., 2009; Salveson, 2011; Watson et al., 2006; Wilson & Jungner, 1968), Krabbe NBS was first initiated in New York State in 2006 (Salveson, 2011; Sano, 2012; Wasserstein et al., 2016). Since 2006, seven additional states (Illinois, Kentucky, Missouri, New Jersey, Ohio, Pennsylvania, and Tennessee) have implemented Krabbe NBS.…”