The specific enzyme defect can be identified using cultured fibroblasts, although in many instances a tentative diagnosis is possible on the clinical features alone. 526 Because of genetic variability, heterogeneity, and pleiotropism, more than 10 clinical syndromes are associated with the 10 enzyme deficiencies. 523–525 As a consequence, mucopolysaccharides accumulate in various tissues and are excreted in the urine. The mucopolysaccharidoses are a group of 10 lysosomal storage diseases that result from the deficiency of specific lysosomal enzymes involved in the degradation of dermatan sulfate, heparan sulfate, or keratan sulfate, singly or in combination.
Patterson MD, FACP, FAAD, in Weedon's Skin Pathology, 2021 Mucopolysaccharidoses The multisystem involvement and progressive nature of MPS syndromes usually requires the complex care provided by medical centers.īibliography is available at Expert Consult. Symptomatic therapy focuses on respiratory and cardiovascular complications, hearing loss, carpal tunnel syndrome, spinal cord compression, hydrocephalus, and other problems ( Table 107.5). Similar effects produce recombinant N-acetylgalactosamine-4-sulfatase in patients with MPS-VI. ERT with recombinant human GALNS improves physical endurance, respiratory function, and daily living activity of patients with MPS-IV. Recombinant iduronate-2-sulfatase is the treatment of choice for MPS-II to ameliorate nonneural manifestations. Consequently, ERT is appropriate for patients with mild CNS involvement or to stabilize extraneural manifestations in young patients before stem cell transplantation. The enzyme does not cross the blood-brain barrier and does not prevent deterioration of neurocognitive function. It reduces organomegaly and ameliorates rate of growth, improves joint mobility, and reduces the number of episodes of sleep apnea and urinary GAG excretion.
Stem cell transplantation does not correct skeletal or ocular anomalies.Įnzyme replacement therapy (ERT) using recombinant α- l-iduronidase has been approved for patients with MPS-I ( Table 107.4). Transplantation in the MPS-VI patient stabilizes or improves cardiac manifestations, posture, and joint mobility. Early transplantation in the MPS-II patient may have the same effect. Transplantation does not significantly improve the neuropsychological outcome of MPS patients with impaired cognition at transplantation. Transplantation before 24 mo and with a baseline mental development index >70 have improved long-term outcome.
Patients with MPS-I who have undergone transplantation before 9 mo of age may show normal cognitive development. Enzyme activity in serum and urinary GAG excretion normalize. Clinical effects are increased life expectancy with resolution or improvement of growth, hepatosplenomegaly, joint stiffness, facial appearance, skin changes, obstructive sleep apnea, heart disease, communicating hydrocephalus, and hearing loss. Hematopoietic stem cell transplantation has resulted in significant clinical improvement of somatic disease in patients with MPS I, II, and VI ( Table 107.4).
Kliegman MD, in Nelson Textbook of Pediatrics, 2020 Treatment