Abstract
Sialidosis is a lysosomal storage disease caused by the deficiency of alpha-N-acetyl neuraminidase-1 (NEU1). Sialidosis is classified into two main clinical variants: Type I, the milder form of the disease, and Type II, which can in turn be subdivided into three forms: congenital, infantile and juvenile. We report herein the clinical, biochemical and molecular characterisation of two patients with Type II sialidosis exhibiting the congenital (P1) and infantile forms (P2). We also review clinical data on the rare Type II forms of sialidosis in the hope of improving understanding of the disorder and facilitating its diagnosis. The genetic characterization of the two patients showed one known [c. 679G > A (p.G227R)] NEU1 missense mutation (detected in P2), and the new c.807 + 1G > A splicing defect (detected in P1), a genetic lesion that is extremely rare in this disease. Interestingly, P2 presented an extremely elevated level of chitotriosidase in plasma. This is the first pathological detection of chitotriosidase in sialidosis patients.
References
Bakker HD, Abeling NGGM, Staalman CR, van Gennip AH (1998) Thirty-years follow up of a patient with sialidosis. J Inherit Metab Dis 21:116
Beck M, Bender SW, Reiter HL, Otto W, Bassler R, Dancygier H, Gehler J (1984) Neuraminidase deficiency presenting as non-immune hydrops fetalis. Eur J Pediatr 143:135–139
Bonten EJ, Arts WF, Beck M, Covanis A, Donati MA, Parini R et al (2000) Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis. Hum Mol Genet 9:2715–2725
Buchholz T, Molitor G, Lukong KE, Praun M, Genzel-Boroviczeny O, Freund M, Pshezhetsky AV, Schulze A (2001) Clinical presentation of congenital sialidosis in a patient with a neuraminidase gene frameshift mutation. Eur J Pediatr 160:26–30
Donati MA, Caciotti A, Bardelli T, Dani C, d’Azzo A, Morrone A, Zammarchi E (2003) Congenital sialidosis Hydrops fetalis Neuraminidase Hydrocephalus Sialidosi congenita Idrope fetale Neuraminidasi Idrocefalo. Ital J Pediatr 29:404–410
Gillan JE, Lowden JA, Gaskin K, Cutz E (1984) Congenital ascites as a presenting sign of lysosomal storage disease. J Pediatr 104:225–231
González González G, Jiménez López I (2006) Anesthetic management of a boy with sialidosis. Rev Esp Anestesiol Reanim 53:253–256
Guibaud P, Cottin X, Maire I, Boyer S, Guibaud S, Coicaud C, Bellon-Azzouzi C, Duvernois JP (1985) Fetal ascites as a manifestation of infantile sialidosis. Significance of a study of oligosaccharides in amniotic fluid. J Genet Hum 33:317–324
Guo Y, He W, Boer AM, Wevers RA, de Bruijn AM, Groener JE, Hollak CE, Aerts JM, Galjaard H, van Diggelen OP (1995) Elevated plasma chitotriosidase activity in various lysosomal storage disorders. J Inherit Metab Dis 18:717–722
Isman F, Hobert JA, Thompson JN, Natowicz MR (2008) Plasma chitotriosidase in lysosomal storage diseases. Clin Chim Acta 387:165–167
Itoh K, Naganawa Y, Matsuzawa F, Aikawa S, Doi H, Sasagasako N et al (2002) Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes. J Hum Genet 47:29–37
Johnson WG, Thomas GH, Miranda AF, Driscoll JM, Wigger JH, Yeh MN, Schwartz RC, Cohen CS, Berdon WE, Koenigsberger MR (1980) Congenital sialidosis: biochemical studies: clinical spectrum in four sibs; two successful prenatal diagnoses. Am J Hum Genet 32:43A
King M, Cockburn F, MacPhee GB, Logan RW (1984) Infantile type 2 sialidosis in a Pakistani family-a clinical and biochemical study. J Inherit Metab Dis 7:91–96
Kelly TE, Bartoshesky L, Harris DJ, McCauley RG, Feingold M, Schott G (1981) Mucolipidosis I (acid neuraminidase deficiency). Three cases and delineation of the variability of the phenotype. Am J Dis Child 135:703–708
Loren DJ, Campos Y, d’Azzo A, Wyble L, Grange DK, Gilbert-Barness E, White FV, Hamvas A (2005) Sialidosis presenting as severe nonimmune fetal hydrops is associated with two novel mutations in lysosomal alpha-neuraminidase. J Perinatol 25:491–494
Lukong KE, Elsliger MA, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Buchholz T, Criado GR, Palmeri S, Pshezhetsky AV (2000) Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. Hum Mol Genet 9:1075–1085
Michelakakis H, Dimitriou E, Labadaridis I (2004) The expanding spectrum of disorders with elevated plasma chitotriosidase activity: an update. J Inherit Metab Dis 27:705–706
Nakamura Y, Takahashi Y, Yamaguchi S, Omiya S, Orii T, Yara A, Gushiken M (1992) Severe infantile sialidosis-the characteristics of oligosaccharides isolated from the urine and the abdominal ascites. Tohoku J Exp Med 166:407–415
Oohira T, Nagata N, Akaboshi I, Matsuda I, Naito S (1985) The infantile form of sialidosis type II associated with congenital adrenal hyperplasia: possible linkage between HLA and the neuraminidase deficiency gene. Hum Genet 70:341–343
Ovali F, Samanci N, Guray A, Akdogan Z, Akdeniz C, Dagoglu T, Petorak I (1998) Congenital sialidosis. Turk J Pediatr 40:447–451
Pattison S, Pankarican M, Rupar CA, Graham FL, Igdoura SA (2004) Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression. Hum Mutat 23:32–39
Penzel R, Uhl J, Kopitz J, Beck M, Otto HF, Cantz M (2001) Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient. FEBS Lett 501:135–138
Riches WG, Smuckler EA (1983) A severe infantile mucolipidosis. Clinical, biochemical, and pathologic features. Arch Pathol Lab Med 107:147–152
Ries M, Deeg KH, Wolfel D, Ibel H, Maier B, Buheitel G (1992) Colour Doppler imaging of intracranial vasculopathy in severe infantile sialidosis. Pediatr Radiol 22:179–181
Rodriguez Criado G, Pshezhetsky AV, Rodriguez Becerra A, Gomez de Terreros I (2003) Clinical variability of type II sialidosis by C808T mutation. Am J Med Genet A 116:368–371
Schiff M, Maire I, Bertrand Y, Cochat P, Guffon N (2005) Long-term follow-up of metachronous marrow-kidney transplantation in severe type II sialidosis: what does success mean? Nephrol Dial Transplant 20:2563–2565
Schmidt M, Fahnenstich H, Haverkamp F, Platz H, Hansmann M, Bartmann P (1997) Sialidosis and galactosialidosis as the cause of non-immunologic hydrops fetalis. Z Geburtshilfe Neonatol 201:177–180
Sergi C, Beedgen B, Kopitz J, Zilow E, Zoubaa S, Otto HF, Cantz M, Linderkamp O (1999) Refractory congenital ascites as a manifestation of neonatal sialidosis: clinical, biochemical and morphological studies in a newborn Syrian male infant. Am J Perinatol 16:133–141
Sergi C, Penzel R, Uhl J, Zoubaa S, Dietrich H, Decker N, Rieger P, Kopitz J, Otto HF, Kiessling M, Cantz M (2001) Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene. Hum Genet 109:421–428
Tabardel Y, Soyeur D, Vivario E, Senterre J (1989) Primary neuraminidase deficiency with prenatal disclosure. Arch Fr Pediatr 46:737–740
Thomas GH (2001) Disorders of glycoprotein degradation: α-mannosidosis, β-mannosidosis, fucosidosis, and sialidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. Mc Graw-Hill, New York, pp 3507–3533
Uhl J, Penzel R, Sergi C, Kopitz J, Otto HF, Cantz M (2002) Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient. FEBS Lett 521:19–23
Winter RM, Swallow DM, Baraitser M, Purkiss P (1980) Sialidosis type 2 (acid neuraminidase deficiency): clinical and biochemical features of a further case. Clin Genet 18:203–210
Yamano T, Shimada M, Matsuzaki K, Matsumoto Y, Yoshihara W, Okada S, Inui K, Yutaka T, Yabuuchi H (1986) Pathological study on a severe sialidosis (alpha-neuraminidase deficiency). Acta Neuropathol (Berl) 71:278–284
Young ID, Young EP, Mossman J, Fielder AR, Moore JR (1987) Neuraminidase deficiency: case report and review of the phenotype. J Med Genet 24:283–290
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Caciotti, A., Di Rocco, M., Filocamo, M. et al. Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients. J Neurol 256, 1911–1915 (2009). https://doi.org/10.1007/s00415-009-5213-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-009-5213-4