Sphingolipidosis is due to defects in
enzymes involved in hydrolysis of
sphingolipids. We analyzed
sphingolipids in tissues from patients with
sphingolipidosis, including
Farber disease (FD,
acid ceramidase deficiency),
Gaucher disease (GD),
Niemann-Pick disease type C (NPDC), and GM1-gangliosidosis (GM1G), using delayed extraction matrix-assisted
laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). Crude
lipids were extracted from about 100 mg wet weight of autopsied tissues, including liver, spleen, cerebrum or cerebellum. After mild alkaline treatment, a
sphingolipid fraction was prepared from the crude
lipids and analyzed by DE MALDI-TOF-MS. The results were as follows: (a) In FD liver both the
ceramide/
sphingomyelin and
ceramide/
monohexosylceramide ratios were significantly high; (b) in both liver and spleen from a GD patient, the
glucosylceramide/
sphingomyelin ratio was raised; (c) in liver from a NPDC patient, the
monohexosylceramide/
sphingomyelin ratio was markedly low, suggesting an increase of
sphingomyelin; and (d) in all tissues examined in the GM1G patient, GM1-gangliosides or asialo-GM1-gangliosides, that are undetectable in a normal control, were increased. In conclusion,
sphingolipids in human tissues could be directly determined by DE MALDI-TOF-MS, with only a small amount of specimens. This method will be useful for the diagnosis and biochemical evaluation of
sphingolipidosis patients.