Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns. CONCLUSIONS: The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.

Neuronal ceroid lipofuscinoses: a clinical and morphological study of 17 patients from Southern Brazil

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited progressive neurodegenerative disorders with presentation from infancy to adulthood. Three main childhood forms can be established on the basis of age of onset, clinical course, and ultrastructural morphology: infantile (INCL), late infantile (LINCL), and juvenile (JNCL). Several variant subtypes have been described. Genetic and biochemical analysis are helping to better understand, diagnose and classify these disorders. We report on clinical, neurophysiological, neuroradiological, and morphological data from 17 patients with different forms (infantile, late infantile, and juvenile ) of neuronal ceroid lipofuscinoses (NCL) evaluated at Hospital de Clínicas de Porto Alegre, Southern Brazil, during 6 years (1992-1997). Seven cases were infantile; 5 were late infantile; and 5 were juvenile NCL. Gender ratio was male:female, 11:6. Age at presentation varied from 2-24 months for INCL; 2,5 to 5 years for LINCL ; and 4-10 years for the JNCL cases. Seizures (6 patients) and psychomotor retardation (1 patient) were the initial symptoms in the INCL group. All the patients in the group of LINCL had the usual findings. JNCL patients manifested different initial symptoms, although tending to follow a similar clinical picture within familial cases. Epidemiological data on the prevalence of NCLs in Brazil are not available, we expect this series of cases to contribute to further research in our population