Sjgren-Larsson综合征成年同胞的表型可变性

Phenotypic variability among adult siblings with Sjgren-Larsson syndrome

Background: Sjgren-Larsson syndrome (SLS) is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene (the gene that encodes microsomal fatty aldehyde dehydrogenase). Cerebral proton magnetic resonance spectroscopy in those with SLS demonstrates an abnormal white matter peak at 1.3 ppm, consistent wit h long-chain fatty alcohol accumulation. Objective: To define the clinical cour se and proton magnetic resonance spectroscopic findings of SLS in adults. Design and Setting: Case series in a tertiary care center. Patients: Six siblings of a consanguineous Arab family with early childhood-onset SLS who carry the 682C→T mutation in the ALDH3A2 gene were reinvestigated in adulthood. Results: The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical c linical and imaging manifestations of SLS, but their severity markedly varied. N eurological involvement was apparently nonprogressive, and its severity showed n o correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings. Conclus ion: These observations document significant clinical variability and the nonpro gressive neurological course of SLS in adult siblings with the same ALDH3A2 geno type, and demonstrate possible correlation of proton magnetic resonance spectros copic changes with age, suggesting unknown pathogenic mechanisms to compensate f or the responsible biochemical defect in this disease.

Background： Sjoegren-Larsson syndrome （SLS） is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene （the gene that encodes microsomal fatty aldehyde dehydrogenase）. Cerebral proton magnetic resonance spectroscopy in those with SIS demonstrates an abnormal white matter peak at 1.3 ppm, consistent with long-chain fatty alcohol accumulation. Objective： To define the clinical course and proton magnetic resonance spectroscopic findings of SIS in adults. Design and Setting： Case series in a tertiary care center. Patients： Six siblings of a consanguineous Arab family with early childhood-onset SLS who carry the 682C→T mutation in the ALDH3A2 gene were reinvestigated in adulthood. Results： The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical clinical and imaging manifestations of SLS, but their severity markedly varied. Neurological involvement was apparently nonprogressive, and its severity showed no correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings. Conclusion： These observations document significant clinical variability and the nonprogressive neurological course of SLS in adult siblings with the same ALDH3A2 genotype, and demonstrate possible correlation of proton magnetic resonance spectroscopic changes with age, suggesting unknown pathogenic mechanisms to compensate for the responsible biochemical defect in this disease.