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Occurrence, distribution, and phenotype of arylsulfatase A (ASA) mutations were investigated in 27 patients with metachromatic leukodystrophy (MLD) from Central Europe, mainly from Austria (n = 15) and Poland (n = 9). Genomic DNA from leukocytes, fibroblasts, or paraffin-embedded, formalin-fixed brain or nerve tissue, respectively, was tested by natural or mutated primer-modulated PCR restriction, fragment length polymorphism for the eight most common European mutations: R84Q, S96F, 459+1G > A, I179S, A212V, 1204+1G > A, P426L, and 1401del11bp. The overall identification rate of unrelated MLD alleles was the highest, in adult (90%), medium in juvenile (50%), and lowest in late infantile (36%) MLD patients. The two common alleles, 459+1G > A and P426L, together accounted for 42% of all 50 unrelated MLD alleles investigated; I179S was observed in 6 of 50 MLD alleles (12%). Thus, I179S was far more frequent than hitherto thought and appears to be a third common mutation in Europe. Moreover, a different allelic distribution between Austrian and Polish juvenile patients was disclosed, indicating genetic heterogeneity of MLD even within Central Europe. The genotype-phenotype correlation suggested by Polten et al. [N Engl J Med 324:18-22, 1991] was not followed by all of our MLD patients. Moreover, some MLD patients with identical ASA mutations presented with different phenotypes. This may be due, at least in some cases, to the presence of an additional mutation on individual mutant alleles. Therefore, prediction of the clinical course from single mutation analysis is not possible.

Gaucher disease is generally caused by a deficiency of the lysosomal enzyme glucocerebrosidase. The degradation of glycosphingolipids requires also the participation of sphingolipid activator proteins. The prosaposin PSAP gene codes for a single protein which undergoes post-translational cleavage to yield four proteins named saposins A, B, C and D. Saposin (SAP-) C is required for glucosylceramide degradation, and its deficiency results in a variant form of Gaucher disease. In this report, we present clinical, biochemical, and molecular findings in a 36-year-old man and his 30-year-old sister with non-neuronopathic Gaucher disease due to SAP-C deficiency. Very high levels of chitotriosidase activity, chemokine CCL18, and increased concentration of glucosylceramide in plasma and normal beta-glucosidase activity in skin fibroblasts were observed in the patients. A molecular genetics study of the PSAP gene enabled the identification of one missense mutation, p.L349P, located in the SAP-C domain and another mutation, p.M1L, located in the initiation codon of the prosaposin precursor protein. The presented findings describe the first cases where the non-neuronopathic Gaucher disease has been definitely demonstrated to be a consequence of SAP-C deficiency. Three previously described cases in the literature displayed a Gaucher type 3 phenotype.

Background and Purposes: Inflammatory factors play an important role in the pathogenesis of ischemic stroke. They may influence circulation during the acute phase of stroke and enhance the ischemic region. Materials and Methods: We examined 51 patients – 36 patients in the early stage of stroke, i.e. the first 24 h after onset. Of these, 15 patients had infection and 21 had no infection during the week preceding stroke. There were 15 patients with noninflammatory diseases in the control group. We analyzed parameters of inflammation such as: activity of serum chitotriosidase by fluorimetric assay, C-reactive proteins (CRP), number of white body cells (WBCs), IgG and fibrinogen. We also assessed the neurological stage according to the Scandinavian Stroke Scale (SSS). Results: In our study, we observed a statistically significant difference (p < 0.05) in the activity of most parameters of inflammation. This difference could be seen in the levels of CRP, number of WBCs and the activity of chitotriosidase, apart from IgG and fibrinogen, between the control group and groups with versus without infection. A significantly increased level of CRP (p < 0.0005) and fibrinogen (p > 0.01) was found on the first day in the stroke group as compared to the control group. The neurological stage on day 4 after stroke, assessed according to the SSS, was significantly worse in the group of patients with infection before stroke than in stroke patients without infection (p < 0.008). Conclusion: These results suggest the importance of active inflammatory processes in the pathogenesis of stroke. We observed increased activity of chitotioridase, a parameter of the inflammatory process, in stroke. This study is one more proof that inflammatory processes caused by infection may influence the occurrence of stroke and worsen its outcome. It could be another step towards understanding immunological processes during the acute phase of stroke. The study may also help establish new diagnostic and therapeutic strategies and could be a useful tool for prophylaxis.