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Salla disease variant in a Dutch patient

Potential value of polymorphonuclear leucocytes for heterozygote detection

  • Metabolic Diseases
  • Published:
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Abstract

A Dutch child with psychomotor retardation, impaired speech, ataxia, sialic acid storage and vacuolized skin fibroblasts and lymphocytes was diagnosed as having free sialic acid storage disease. Slight corneal opacities, pale optic disks at the fundus oculi and vertebral abnormalities, not earlier reported in Salla disease, were peculiar to this case. Free sialic acid was about tenfold increased in urine and cultured fibroblasts, without changes in the glycoconjugate-bound sialic acid pool. A subsequent pregnancy of the patient's mother was monitored by assay of sialic acid in chorionic villi and amniotic fluid. An unaffected foetus was predicted. Sialic acid was also assayed in peripheral blood total leucoyctes, and in mononuclear and polymorphonuclear (PMN) leucocyte subpopulations. Each of these leucocyte fractions from the patient showed 10- to 30-fold increase in sialic acid content. The PMN subpopulation provided the most restricted range of control values and showed slightly increased values for the patient's parents. These results suggest that the assay of sialic acid in PMN might be useful for the identification of heterozygotes in sialic acid storage disease. Studies on a larger number of obligate heterozygotes are needed to confirm this observation.

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Abbreviations

ISSD:

infantile sialic acid storage disease

PMN:

polymorphonuclear leucocytes

SASD:

stalic acid storage disease

TLC:

thin layer chromatography

References

  1. Aula P, Autio S, Raivio KO, Rapola J, Thoden CJ, Koskela SL, Yamashima I (1979) “Salla disease”: a new lysosomal storage disorder. Arch Neurol 36:88–94

    PubMed  Google Scholar 

  2. Baumkotter J, Cantz M Mendla K, Baumann W, Friebolin H, Gehler J, Spranger J (1985) N-acetylneuraminic acid storage disease. Hum Genet 71:155–159

    PubMed  Google Scholar 

  3. Clements PR, Taylor JA, Hopwood JJ (1988) Biochemical characterization of patients and prenatal diagnosis or sialic acid storage disease in three families. J Inherited Metab Dis 11:30–44

    Article  PubMed  Google Scholar 

  4. Denny PC, Denny PA, Allerton SE (1983) Determination of sialic acid using 2-thiobarbituric acid in the absence of hazardous sodium arsenite. Clin Chim Acta 131:333–336

    Article  PubMed  Google Scholar 

  5. Echenne B, Vidal M, Maire I, Michalski JC, Baldet P, Astruc J (1986) Salla disease in one non-finnish patient. Eur J Pediatr 145:320–322

    Article  PubMed  Google Scholar 

  6. Fois A, Balestri P, Farnetani MA, Mancini GMS, Borgogni P, Margollicci MA, Molinelli M, Alessandrini C, Gerli R (1987) Free sialic acid storage disease: a new italian case. Eur J Pediatr 146:195–198

    PubMed  Google Scholar 

  7. Galjaard H (ed) (1980) Genetic metabolic diseases Early diagnosis and prenatal analysis. Elsevier Scientific Publishing Co, Amsterdam

    Google Scholar 

  8. Hancock LW, Thaler MM, Horwitz AL, Dawson G (1982) Generalized N-acetylneuraminic acid storage disease: quantitation and identification of the monosaccharide accumulating in brain and other tissues. J Neurochem 38:803–809

    PubMed  Google Scholar 

  9. Lake BD, Young EP, Nicolaides K (1989) Prenatal diagnosis of infantile free sialic acid storage disease in a twin pregnancy. J Inherited Metab Dis 12:152–156

    Article  PubMed  Google Scholar 

  10. Mancini GMS, Hoogeveen AT, Galjaard H, Mansson JE, Svennerholm L (1986) Ganglioside GM1 metabolism in living fibroblasts with β-galactosidase deficiency. Hum Genet 73:35–38

    Article  PubMed  Google Scholar 

  11. Mancini GMS, Verheijen FW, Galjaard H (1986) Free N-acetylneuraminic acid (NANA) storage disorders: evidence for defective NANA transport across the lysosomal membrane. Hum Genet 73:214–217

    Article  PubMed  Google Scholar 

  12. Mancini GMS, De Jonge HR, Galjaard H, Verheijen FW (1989) Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane: evidence for a group-specific transport system for acidic monosaccharides. J Biol Chem 264:15247–15254

    PubMed  Google Scholar 

  13. Mancini GMS, Beerens CEMT, Aula PP, Verheijen FW (1991) Sialic acid storage diseases: a multiple lysosomal transport defect for acidic monosaccharides. J Clin Invest 87:1329–1335

    PubMed  Google Scholar 

  14. Mancini GMS, Verheijen FW, Beerens CEMT, Renlund M, Aula P (1991) Sialic acid storage disorders: observations on clinical and biochemical variation. Dev Neurosci 13:327–330

    PubMed  Google Scholar 

  15. Mendla K, Baumkotter J, Rosenau C, Ullrich-Bott B, Cantz M (1988) Defective lysosomal release of glycoprotein-derived sialic acid in fibroblasts from patients with sialic acid storage disease. Biochem J 250:261–267

    PubMed  Google Scholar 

  16. Michalski JC, Montreuil J, Strecker G (1983) A thin-layer chromatographic technique for screening for sialuria. Clin Chim Acta 129:99–101

    Article  PubMed  Google Scholar 

  17. Paschke E, Trinkl J, Erwa W, Pavelka M, Mutz I, Roscher A (1986) Infantile type of sialic acid storage disease with sialuria. Clin Genet 29:417–424

    PubMed  Google Scholar 

  18. Paschke E, Hofler G, Roscher A (1986) Infantile sialic acid storage disease: the fate of biosynthetically labeled N-acetyl-[3H]neuraminic acid in cultured human fibroblasts. Pediatr Res 20:773–777

    PubMed  Google Scholar 

  19. Renlund M (1984) Clinical and laboratory diagnosis of Salla disease in infancy and childhood. J Pediatr 104:232–236

    PubMed  Google Scholar 

  20. Renlund M, Aula P (1987) Prenatal detection of Salla disease based upon increased free sialic acid in amniocytes. Am J. Med Genet 28:377–384

    Article  PubMed  Google Scholar 

  21. Renlund M, Aula P, Raivio KO, Autio S, Sainio K, Rapola J, Koskela SL (1983) Salla Disease: new lysosomal storage disorder with disturbed sialic acid metabolism. Neurology 33:57–66

    PubMed  Google Scholar 

  22. Renlund M, Tietze F, Gahl WA (1986) Defective sialic acid regress from isolated fibroblast lysosomes of patients with Salla disease. Science 232:759–762

    PubMed  Google Scholar 

  23. Seppala R, Renlund M, Bernardini I, Tietze F, Gahl WA (1990) Renal handling of free sialic acid in normal humans and patients with Salle disease or renal disease. Labor Invest 63:197–203

    Google Scholar 

  24. Roos D, Loos JA (1970) Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. Biochem Biophys. Acta 222:565–582

    PubMed  Google Scholar 

  25. Smolin LA, Clark KF, Schneider JA (1987) An improved method for heterozygote detection of cystinosis, using polymorphonuclear leucocytes. Am J Hum Genet 41:266–275

    PubMed  Google Scholar 

  26. Sperl W, Gruber W, Quatacker J, Monnens L, Thoenes W, Fink FM, Paschke E (1990) Nephrosis in two siblings with infantile sialic acid storage disease. Eur J Pediatr 149:477–482

    PubMed  Google Scholar 

  27. Stevenson RE, Lubinsky M, Taylor HA, Wenger DA, Schroer RJ, Olmstead PM (1983) Sialic acid storage disease with sialuria: clinical and biochemical features in the severe infantile type. Pediatrics 72:441–449

    PubMed  Google Scholar 

  28. Tietze F, Seppala R, Renlund M, Hopwood JJ, Harper GS, Thomas GH, Gahl WA (1989) Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in fibroblasts of patients with infantile free sialic acid storage disease. J Biol Chem 264:15316–15322

    PubMed  Google Scholar 

  29. Tondeur M, Libert J, Vamos E, Hoff F van, Thomas GH, Strecker G (1982) Infantile form of sialic acid storage disorder: clinical, ultrastructural and biochemical studies in two siblings. Eur J Pediatr 139:142–147

    Article  PubMed  Google Scholar 

  30. Vamos E, Libert J, Elkhazen N, Jauniaux E, Hustin J, Wilkin P (1986) Prenatal diagnosis and confirmation of infantile sialic acid storage disease. Prenat Diagn 6:437–446

    PubMed  Google Scholar 

  31. Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H (1985) Human placental neuraminidase. Activation, stabilization and association with its ‘protective’ protein. Eur J Biochem 149:315–321

    Article  PubMed  Google Scholar 

  32. Warren L (1959) The thiobarbituric acid assay of sialic acids. J Biol Chem 234:1971–1975

    PubMed  Google Scholar 

  33. Wolburg-Buchholz K, Schlote W, Baumkotter J, Cantz M, Holder H, Harzer K (1985) Familial lysosomal storage disease with generalized vacuolization and sialic aciduria. Sporadic Salla disease. Neuropediatrics 16:67–75

    PubMed  Google Scholar 

  34. Ylitalo V, Hagberg B, Rapola J, Mansson JE, Svennerholm L, Sanner G, Tonnby B (1986) Salla disease variants. Sialylaciduric encephalopathy with increased sialidase activity in two non-Finnish children. Neuropediatrics 17:44–47

    PubMed  Google Scholar 

  35. Zhao H, Diggelen OP van, Thoomes R, Huijmans J, Young E, Marurczak T, Kleijer WJ (1990); Prenatal diagnosis of Morquio disease type A using a simple fluorimetric enzyme assay. Prenat Diagn 10:85–91

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Erasmus University, P.O.Box 1738, NL-3000 DR, Rotterdam, The Netherlands

    G. M. S. Mancini & F. W. Verheijen

  2. Department of Clinical Genetics, Erasmus University, P.O.Box 1738, NL-3000 DR, Rotterdam, The Netherlands

    P. Hu, O. P. van Diggelen, H. C. Janse & W. J. Kleijer

  3. Clinical Genetics Centre, Utrech, The Netherlands

    F. A. Beemer

  4. Neuromuscular Laboratory, Academic Hospital, Utrecht, The Netherlands

    F. G. I. Jennekens

Authors
  1. G. M. S. Mancini
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  2. P. Hu
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  3. F. W. Verheijen
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  4. O. P. van Diggelen
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  5. H. C. Janse
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  6. W. J. Kleijer
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  7. F. A. Beemer
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  8. F. G. I. Jennekens
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Mancini, G.M.S., Hu, P., Verheijen, F.W. et al. Salla disease variant in a Dutch patient. Eur J Pediatr 151, 590–595 (1992). https://doi.org/10.1007/BF01957729

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  • DOI: https://doi.org/10.1007/BF01957729

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