However, clinical benefit varies, both between patients and between different organs in the same patient. Overall, survival is significantly prolonged, and when initiated early, decline of neurocognition can be stabilized. Clinical effect is evident in reduced facial coarseness, joint mobility, and reduction in sleep apnea, cardiac disease, and hearing loss. A number of experimental strategies are currently under development to reduce the remaining burden of disease.Īllogeneic HSCT is considered the gold standard for treatment of Hurler syndrome and can alleviate a number of disease symptoms and increase the patient’s life span, especially when performed before the age of 2 years and prior to cognitive impairment. Bones, eyes, and heart valves prove to be especially resistant to treatment. Moreover, the therapeutic effect in some systems appears to wear off after several years. To overcome this limitation, implementation of MPS I in newborn screening programs is strongly recommended.
Therefore, treatment must commence as early as possible for maximum effect and diagnostic delay-due to the nonspecific nature of early symptoms-limits treatment success. Both treatments may at best prevent the development or worsening of abnormal function and somatic complications but cannot revert already existing symptoms. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA).
Finally, we highlight alternative and emerging treatments for the most common disease manifestations. Where relevant, results of animal models of MPS I will be included. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs.
IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively).