## 3 MALDI Non-Imaging MS Analysis of GSLs
### MALDI Non-Imaging MS Analysis of GSLs in Pathology
#### 3.5.1 GSLs in Storage Diseases
This investigation underscores the utility of AP-MALDI as a straightforward technique for accurate identification of ganglioside ceramide moieties without subjecting the samples to vacuum conditions that might impact their structural integrity. However, it is important to note that this method is suitable solely for purified samples. 3. Spielmeyer-Vogt type amaurotic idiocy (Niemann-Pick disease type C)  
Niemann-Pick disease type C (NPC) represents a recessive autosomal lipid storage disorder that encompasses a diverse range of clinical manifestations. At the cellular level, this condition is marked by the buildup of unesterified cholesterol and glycolipids within the lysosomal/late endosomal system [187]. Taketomi et al. [142] discovered that the anomalous composition of long-chain bases in GM1 within brain tissues from a patient diagnosed with Spielmeyer-Vogt type amaurotic idiocy could potentially signify an altered metabolism of GM1's long-chain bases. Their examination of GM1 samples obtained from brain tissues of individuals across various diseases and age groups demonstrated a significant rise in the portion of d20:1 (icosasphin-gosine) and d20 (icosasphin-ganine) relative to the total sphingosine bases until adolescence or adulthood. Beyond this point, this proportion remained relatively stable, slightly surpassing 50%. This ratio was notably higher compared to what was observed previously in GM1 samples from adult mammalian brains (such as monkey, dog, bear, pig, and rabbit). Interestingly, the LCB composition of GM1 in two samples of Spielmeyer-Vogt type amaurotic idiocy exhibited abnormal values, despite the absence of GM1 accumulation in the brain tissue, suggesting intricate interactions between GSL metabolism and disease progression. Specifically, the LCB composition showed d18:1 at 57.8% and 54.9%, d18 at 3.1% and 2.5%, d20:1 at 37.3% and 40.3%, and d20 at 1.8% and 2.3%, respectively. The deviation in the LCB composition of GM1 suggests an altered metabolism of the long-chain bases, which can have far-reaching implications for cellular function and signaling processes. With regard to the liver tissue sample from a patient with Spielmeyer-Vogt type amaurotic idiocy, Fujiwaki et al. [137] found no significant changes in the mass spectrum, compared to the control sample. 4. Sudanophilic leukodistrophy  
Leukodystrophies are genetic disorders affecting the central nervous system and peripheral nerves, characterized by the degeneration of myelin sheaths. The term \"leukodistrophy\" means deterioration of the white matter within the brain. The underlying defect in these disorders is directly linked to the maintenance and synthesis of myelin membranes. The majority of leukodystrophies manifest during childhood or adolescence, are currently incurable, and exhibit a progressive trajectory that ultimately leads to premature mortality [188]. A tissue specimen obtained from a patient diagnosed with satanophilic leukodystrophy underwent MALDI-TOF MS analysis to determine the GM1 composition. The GM1 was isolated intact following the same procedures and sample preparation technique previously outlined by Taketomi et al. [162]. Molecular ions were identified at \(m/z\) 1545.42 for GM1 (d18:1/C18:0) [\(\mathrm{M-H}\)]\({}^{-}\) and \(m/z\) 1573.46 for GM1 (d20:0/C18:0). Additionally, GM1 (d18:0/C18:0) and (d20:0/C18:0) were also detected by evaluating the differences between calculated theoretical values and the identified values of three isotopically resolved peaks for each GM1 compound (\(m/z\) 1546.3, 1547.32, and 1548.28 for GM1 \(m/z\) 1545.32; and \(m/z\) 1574.35, 1575.4, and 1576.39 for GM1 \(m/z\) 1573.37) [162]. As a result, the composition of the long-chain base of GM1 was determined as follows: d18:1 (44.2%), d18:0 (2.3%), d20:1 (49.9%), and d20:0 (3.6%). The data revealed a typical spectrum for GM1-isolated species with a normal proportion of the sphingoid bases composition, according to a normal evolution [142], highlighting the diversity of sphingosine structures within GM1 gangliosides.