Krabbe´s disease: case report on the phenotypic spectrum of a multifaceted metabolic leukodystrophy

Abstract

Introduction: Krabbe's disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive disorder caused by galactocerebrosidase (GALC) deficiency. Its diagnosis is based on an enzymatic test followed by molecular genetic study of the GALC gene. Clinical manifestations are diverse and include motor alterations, cognitive involvement with irritability, spasticity and developmental regression, with death at a very early age in the classic infantile form. In late-onset forms, the phenotypes are more attenuated with gait abnormalities and slower progression. Objectives: To demonstrate the phenotypic variability of a Brazilian cohort considering the multiethnic character of this population, and to emphasize=point out the importance of early diagnosis for the possibility of treatment, since there is evidence of improvement in evolution and prognosis. Case Study: Three cases of male patients with Globoid Cell Leukodystrophy are presented, all children of non-consanguineous parents, with molecular diagnosis and without common variation, reinforcing the multiethnic character of the Brazilian population. The onset age of clinical manifestations varied (one month, eight months and  two years) and the disease was diagnosed between three months and wo years of age. The patients had neuropsychomotor development delay, different neurological manifestations and brain magnetic resonance imaging was similar between them. The study patients did not receive treatment because they were not diagnosed early and two of them had complications of the disease and died. Conclusion: Globoid Cell Leukodystrophy presents a high phenotypic variability with multiple manifestations. Furthermore, the early diagnosis of the disease is a challenge that directly impacts the prognosis and the only therapy currently available; bone marrow transplantation. Additionally, the accurate diagnosis of the disease enables family genetic counseling and helps to improve the patient's rehabilitation care.