AB126. Enzyme replacement therapy in patient with mucopolysaccharidosis type I: a case report

Background and objective: Mucopolysaccharidosis I (MPS I) is a rare, recessively inherited, lysosomal storage disorder caused by deficiency on the enzyme α-L-iduronidase. This defect results in accumulation of heparan and dermatan sulfate in different tissues and organs due to a deficiency in the catabolism of glycosaminoglycans. The overall incidence of MPS I is 0.99-1.99/100,000 live births. Enzyme replacement therapy (ERT) with recombinant α-L-iduronidase (laronidase) has shown to significantl improve the quality of life in children. To describe clinical characteristics, enzyme activity and genetic finding in the first Vietnamese patient with MPS type I with aldurazyme replacement therapy.

Methods: Clinical features, biochemical finding, enzyme activity, mutation analysis and management in a 4 years 6-month-old girl was study. Based on analysis of a patient’s clinical symptoms associated with enzyme α-L-iduronidase activity measurement in leukocyte, the diagnosis of MPS type I was therefore made. Genomic DNAs were extracted from peripheral blood leukocytes from the patient and identify mutation of IDUA gene, 14 exons and their intronic boundaries of the IDUA gene were sequenced using genomic DNA from the patient. The patient has been treated with aldurazyme infusion every week with the dose of 0.58 mg/kg/week.

Results: A 4 years 6-month-old girl was presented with joint stiffness at 2 years old. She was admitted with the features of short status, coarse facial, corneal clouding, carpel tunnel syndrome and joint stiffness, kyphosis, abdominal distension, palpable liver at 3 cm below the costal margin, sleep disturbances/snoring. Laboratory showed: hearing lost at right ear in acoumetry, hepatosplenomegaly in ultrasound with right liver length of 117 mm, spleen length of 89 mm, a 6-minute walk test distance of 158.6 m, α-I-duronidase 0.43 nmoL/mg Prot/hrs (normal: 41.8±15.9), urine glycosaminoglycan (GAG) of 508.83 mg/g creatinine (normal: 10.74-112.02). PCR sequencing of IDUA gene showed a novel heterozygous sequence variant c.1046A>G (p.Asp349Gly). After 6 months: more active, decreasing of wheezing in sleep, a 6-minute walk test distance of 252 m, ultrasound showed normal live and spleen size, urine GAGs of 61.18 mg GAGs/g Creatinine.

Conclusions: Enzyme therapy can improve of clinical manifestation which will lead to improvements in life expectancy and quality of life in MPS I patients.

Keywords: Mucopolysaccharidosis type I; hurler; aldurazyme therapy in MPS I