title: Does galactocerebrosidase activity predict Krabbe phenotype?
abstract: This study sought to determine whether galactocerebrosidase activity is predictive of Krabbe onset age, or of survival from onset when controlling for age at onset of signs. We analyzed data on 55 symptomatic patients from the Hunter James Kelly Research Institute's World-Wide Registry. They were tested for galactocerebrosidase activity at Jefferson Medical College (Philadelphia, PA), using survival models in a path model context. Higher galactocerebrosidase activity was predictive of later symptom onset times (P = 0.0011), but did not predict survival after symptom onset (P = 0.9064) when controlling for the logarithm of age at onset. No child with early infantile (aged 0-6 months) phenotype demonstrated galactocerebrosidase activity >0.1 nmol/hour/mg protein. Survival times within a given phenotype did not vary with galactocerebrosidase activity. Although low galactocerebrosidase activity does not predict phenotype, higher activity in the abnormal range (>0.1 nmol/hour/mg protein in this sample) was not identified in the early infantile variant. Galactocerebrosidase activity may be important to consider when predicting phenotype in the newborn screening population. Our findings provide empiric evidence that the upper end (0.15 nmol/hour/mg protein) of the high-risk galactocerebrosidase group in the New York State newborn screening program is conservatively appropriate.
authors.affiliation: Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Kabir
authors.initials: K
authors.lastname: Jalal
authors.forename: Randy
authors.initials: R
authors.lastname: Carter
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Amy
authors.initials: A
authors.lastname: Barczykowski
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Duffner
mesh_terms: D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation / Q000502:physiology; D005698:Galactosylceramidase / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D012042:Registries; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D005698:Galactosylceramidase