engleski

Two siblings with sialidosis type II: clinical, biochemical and neuroradiological study

Background: Lysosomal neuraminidase is a key enzyme for the intralysosomal catabolism of sialoglycoconjugates. It is deficient in two neurodegenerative lysosomal disorders: sialidosis (structural deficit in the neuraminidase gene) and galactosialidosis (loss of neuraminidase activity secondary to PPCA deficiency). Sialidosis is classified as sialidosis type 1: normomorphic (cherry red spot-myoclonus syndrome) and type 2: dysmorphic, infantile and juvenile form. Aim: We present clinical, biochemical, and neuroradiological findings in two siblings, a 20-year old girl and a 15-year old boy affected with type II sialidosis. They are the first cases of sialidosis in Croatia confirmed by enzyme activity. Results: Diagnosis of MPS IV was suspected at the age of 3-5 years based on clinical and radiographic findings. Both sibs presented with coarse facial features, short trunk and relatively long limbs, impaired hearing, dysostosis multiplex and average intellectual development. By the age of 11 years the children developed myoclonic seizures, ataxia and dysarthria. Neither of them exhibited the classic cherry-red macular spot, which is remarkable, because this macular abnormality is almost invariably present in sialidosis patients. Brain CT scans showed diffuse cortical atrophy. Due to the development of contractures both sibs became immobile between the age of 15 and 20 years. Biochemical investigation showed normal or elevated excretion of glycosaminoglycans in urine (chondroitin-6 and chondroitin-4 sulfate, traces of heparan or keratan sulfate, no dermatan sulfate), normal catalytic activities of alpha-iduronidase, GalNAc-6-S sulfatase, beta-galactosidase, arylsulfatase A and B, beta-glucuronidase, alpha-fucosidase, hexosaminidase A and B in skin fibroblasts and leukocytes. Diagnosis was made based on elevated levels of sialooligosaccharides in the urine and markedly reduced neuraminidase activity in skin fibroblasts and leukocytes. Conclusions: The presented patients illustrate the clinical heterogeneity of neuraminidase deficiency. Clinical presentation presumably correlates with the type of the sialidase molecular defects and residual catalytic activity of the mutant neuraminidases. 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.

sialidosis; neuraminidase; lysosomal disorders

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