Mucopolysaccharidosis I - clinical manifestations in 24 children from the Czech Republic and Slovakia
Abstract
Mucopolysaccharidosis I (MPS I) is severe metabolic storage disease caused by impaired function of ?-L-iduronidase. The aim of this study is to describe clinical symptoms, natural course and to evaluate results of treatment in Czech and Slovak children with MPS I.
Methods: Study group consists of 24 children from 23 families. In all children diagnosis of MPS I was confirmed on enzymatic level and in 22 children on molecular level.
Results: First symptoms of disease - hepatosplenomegaly, craniofacial dysmorphy, corneal clouding and psychomotor delay - were observed in all patients. The most of them have macrocephaly (11/21) and skeletal changes - dysostosis multiplex (21/23).
Cardiomyopathy with valves impairment (16/21), hearing impairment (9/18), joint stiffness (19/22) and carpal tunnel syndrome (7/23) belongs to later symptoms. All children had increased glycosaminoglycans excretion in urine and decreased activity of ?-L-iduronidase in isolated leucocytes.
Two mutations in gene ?-L-iduronidase were prevalent, the mutation p.W402X was found in 9 and the mutation p.Q70X in 7 children. Hematopoietic stem cell transplantation (HSCT) was performed in 7 children, in 5 of them with good clinical result. 6 children with milder form of disease were treated by a long-lasting enzyme replacement therapy (ERT) with good therapeutic effect, but one patient died due to complication after neurosurgery intervention for compression of cervical spinal cord.
The most of children without therapy died (7/11). Conclusion: Diagnostic of MPS I in early phases of disease improves prognosis, because correct therapy (HSCT or ERT) can be chosen.
Prognosis for children with later diagnosis is very unfavourable. The advance diagnosis is very important also for prenatal diagnostic in affected families.