## 6 Farber disease  
Farber disease (also known as Farber lipogranulomatosis) is a hereditary lysosomal storage disorder inherited in an autosomal recessive manner. It arises from a deficiency in acid ceramidase, an enzyme critical for cellular processes, resulting in distinct clinical manifestations. The clinical phenotypes associated with Farber disease vary, with children experiencing severe neurological issues often succumbing in infancy, while individuals with milder neurological involvement facing progressive joint deformation, contractures, subcutaneous nodules, periarticular granulomas, hoarse voice, and eventually respiratory insufficiency. The outcome of the disease is respiratory failure and eventual death in the third or fourth decade of life for those without severe neurological symptoms [190].  
Derived from liver tissue samples of an individual with Farber disease (Voyager Elite XL (PerSeptive Biosystem, Framingham, MA, USA) DE-MALDI-TOF MS, 2.5 DHB and CHCA matrices, positive ion mode), ceramides with different fatty acid carbon numbers were identified, which were not detectable in the control samples: ceramide (d18:1/C20), as \(\left[\mathrm{M+Na}\right]^{+}\) at \(m/z\) 616, ceramide (d18:1/C21), as \(\left[\mathrm{M+Na}\right]^{+}\) at \(m/z\) 630 and ceramide (d18:1/C22), as \(\left[\mathrm{M+Na}\right]^{+}\) at \(m/z\) 644. The elevated accumulation of ceramide was further indicated by the notably high ratios of ceramide/sphingomyelin and ceramide/monohexosylceramide [137]. Fujiwaki T. et al. [137] noted the presence of abnormal ceramide accumulation and altered lipid ratios in human tissue samples from individuals with Farber disease, highlighting the crucial role of GSLs, particularly ceramics, in cellular health and function. The disruption of these lipids can contribute to the pathogenesis of the disorder and may be associated with clinical symptoms.  
Fabry disease is an X-linked inherited lysosomal storage disorder caused by a deficiency of the enzyme \(\alpha\)-galactosidase A, which leads to the accumulation of Gb3 in various tissues, including nerves, dorsal root ganglia, the walls of capillary vessels, renal glomerular and tubular epithelial cells, as well as cardiomyocytes. Clinically, it is characterized by chronic pain, gastrointestinal disturbances, acroparesthesia, distinctive skin lesions, progressive renal dysfunction, cardiomyopathy, and strokes [191]. Taketomi et al. [162] performed an extraction of GSLs using the method of saponification described earlier, for the purpose of examining multiple sphingolipids originating from a single sample (DE-MALDI-TOF MS, Voyager Elite XL (PerSeptive Biosystem, Framingham, MA, USA), 2,5 DHB matrix, positive ion mode). Employing the necrotic femoral head tissue from an individual affected by Fabry disease and a control subject, the mass spectra indicated an accumulation of Gb3 Cer, with the highest intensity of the peaks at \(m/z\) 1130.99--Gb3 Cer (d18:1/C22:0), as \(\left[\mathrm{M+Na}\right]^{+}\), \(m/z\) 1156.98--Gb3 Cer (d18:1/C24:1), as \(\left[\mathrm{M+Na}\right]^{+}\) and \(m/z\) 1159.01--Gb3 Cer (d18:1/C24:0), among sphingomyelin (at \(m/z\) 703, 725, 758, 788, 810, 824, 836, 838, and 846) and GlcCer (at \(m/z\) 778, 834), which were of lower intensities. These peaks highlighted the specific molecular signatures of the disease.  
The scope of the study is to prove that using MS it is possible to determine multiple GSLs from a single sample, with a quick method of sample preparation.