Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review
The majority of newborns screening positive for Krabbe disease have not exhibited the expected early infantile phenotype, with most clinically normal despite low galactocerebrosidase activity and two mutations. Most are expected to develop the later onset phenotypes. The World-Wide Krabbe Registry was developed in part to expand our understanding of the natural history of these rare variants. As of June 2011, 122 patients were enrolled in the registry: 62% manifested early infantile onset (previously reported), 10% manifested onset at 7-12 months (late infantile), 22% manifested onset at 13 months to 10 years (later onset), and 5% manifested adolescent/adult onset. Data on disease course, galactocerebrosidase activity, DNA mutations, and results of neurodiagnostic studies were obtained from questionnaires and medical records. Initial signs (late infantile) included loss of milestones and poor feeding, whereas later onset and adolescent/adult phenotypes presented with changes in gait. Elevated cerebrospinal fluid protein and abnormal magnetic resonance imaging results were present in most, but not all, patients at diagnosis. Phenotypic variability occurred in four sibships. Five-year and 10-year survivals for all later onset phenotypes were at least 50%. The later onset Krabbe phenotypes differ from those with early infantile disease, but no specific predictor of phenotype was identified.