Naslov
Sialidosis type II: clinical, biochemical, and neuroradiological study of two siblings

Autori
Barišić, Ingeborg ; Jadrešin, Oleg ; Fumić, Ksenija ; Ligutić, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
The Second European-American Intensive Course in Clinical and Forensic Genetics / Primorac, Dragan - Zagreb, 2001

Skup
2nd European-American Intensive Course in Clinical and Forensic Genetics

Mjesto i datum
Dubrovnik, Hrvatska, 03.09.2001. - 14.09.2001

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
sialidosis type II; neuraminidase deficiency; lysosomal storage disease

Sažetak
Sialidosis (neuraminidase deficiency) is a lysosomal storage disease characterized by the accumulation and/or excretion of sialic acid covalently linked to oligosaccharides and/or glycoproteins. Neuraminidase (alpha-NAGA) has an essential role in the removal of terminal sialic acid residues form sialoglycoconugates. This enzyme occurs in a complex with beta-galactosidase and protective protein/cathepsin A (PPCA) and is deficient in 2 genetic diseases: sialidosis (structural deficit in the neuraminidase gene) and galactosialidosis (loss of neuraminidase activity secondary to PPCA deficiency). The disease was classified as sialidosis type 1 - normomorphic (cherry red spot-myoclonus syndrome) and type 2 - dysmorphic, infantile and juvenile form. Here we present clinical, biochemical, and neuroradiological findings in two siblings, 20-year old girl and 15-year old boy affected with type II sialidosis. These two are the first cases of sialidosis in Croatia to be confirmed by enzyme activity. In both patients diagnosis of MPS IV was suspected at the age of 3-5 yrs based on clinical and radiographic findings. They presented with short trunk and relatively long limbs, corase facial features, impaired hearing, dysostosis multiplex and average intellectual development. By the age of 11 years both children developed myoclonic seizures, ataxia and dysarthria. Neither macular cherry-red spot nor hepatosplenomegaly were observed. Brain CT scan showed diffuse cortical atrophy. Both children developed contractures and became immobile between the age of 15 and 20 yrs. Biochemical investigations showed normal or elevated excretion of glycosaminoglicans in urine (chondroitin-6 and chondroitin-4 sulphate, traces of heparan or keratan sulphate, no dermatan sulphate), normal catalytic activities of alpha-iduronidase, GalNAc-6-S sulphatase, beta-galactosidase, arylsulphatase A and B, beta-glucuronidase, alfa-fucosidase, hexosaminidase A and B in skin fibroblasts and leukocytes. Diagnosis was made by finding of elevated levels of sialooligosaccharides in the urine and profound alpha-NAGA deficiency in skin fibroblasts and leukocytes. Presented patients illustrate the clinical variability of neuraminidase deficiency. Clinical presentation presumably correlates with the type of the sialidase molecular defects. Therefore identification of the specific mutations responsible for the enzyme deficiency and the characterisation of the molecular defects are needed to better understand the genotype-phenotype correlation in sialidosis patients.

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita

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