Diagnosing Mucopolysaccharidosis type IV a by the fluorometric assay of N-Acetylgalactosamine-6-sulfate sulfatase activity
نویسندگان
چکیده
BACKGROUND Mucopolysaccharidosis type IVA, also known as Morquio A or MPS IV A, is an autosomal recessive disease caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The loss of GALNS activity leads to the impaired breakdown of glycosaminoglycans (GAGs) keratan sulfate and chondroitin-6-sulfate. The accumulation of GAGs results in multiple organ damage. The accurate and early diagnosis of this disorder helps enhance the effectiveness of the treatment. The present study uses a pre-designed protocol for testing GALNS activity in the leukocytes of Iranian patients with MPS IV A and their parents and compares it with healthy controls. METHODS Patients with MPS IVA previously diagnosed through the measurement of enzyme activity or genetic analysis entered the study. Leukocytes were obtained from the heparinized blood of the participants. The GALNS activity was measured by a fluorometric method using 4-methylumbelliferyl-β-D-galactoside-6-sulfate (4MU-G6S) as the substrate and proper buffer solutions and calibrators. RESULTS The GALNS activity (nmol/17 h/mg protein) was reported as 0-7.4 in the MPSIV A patients, as 19.85-93.7 in their parents and as 38.4-164 in the healthy controls. Statistically significant differences were observed between the three groups in terms of enzyme activity. There were no significant differences in enzyme activity by age. The female subjects in both the patient and parents groups showed lower enzyme activity compared to the male subjects. CONCLUSION The fluorometric method was validated for the measurement of GALNS activity in leukocyte samples and identifying Iranian patients with MPS IV A.
منابع مشابه
Development of a fluorometric microtiter plate based enzyme assay for MPS IVA (Morquio type A) using dried blood spots
Mucopolysaccharidosis type IVA or Morquio type-A disease is a hereditary lysosomal storage disorder caused by deficient activity of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The disease is caused by lysosomal accumulation of unprocessed glycosaminoglycans (GAGs) that manifests with severe to mild skeletal and cardiopulmonary abnormalities. We have developed a modif...
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Mucopolysaccharidosis type IV-A (Morquio A disease) is an autosomal recessive lysosomal storage disease caused by mutations in the gene encoding the N-acetylgalactosamine-6-sulfate sulfatase, that results in impaired catabolism of two glycosaminoglycans, chondroitin-6-sulfate and keratan sulfate. Clinical presentations reflect a spectrum of progression from a severe phenotype to an attenuated e...
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