Mucopolysaccharidosis Type I

Abstract

Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of α-l-iduronidase, leading to the storage of dermatan and heparan sulfate. There is a broad phenotypical spectrum with the presence or absence of neurological impairment. The classical form is known as Hurler syndrome, the intermediate form as Hurler–Scheie, and the most attenuated form is known as Scheie syndrome. Phenotype seems to be largely influenced by genotype. Patients usually develop several somatic symptoms such as abdominal hernias, extensive dermal melanocytosis, thoracolumbar kyphosis odontoid dysplasia, arthropathy, coxa valga and genu valgum, coarse facial features, respiratory and cardiac impairment. The diagnosis is based on the quantification of α-l-iduronidase coupled with glycosaminoglycan analysis and gene sequencing. Guidelines for treatment recommend hematopoietic stem cell transplantation for young Hurler patients (usually at less than 30 months of age). Intravenous enzyme replacement is approved and is the standard of care for attenuated—Hurler–Scheie and Scheie—forms (without cognitive impairment) and for the late-diagnosed severe—Hurler—cases. Intrathecal enzyme replacement therapy is under evaluation, but it seems to be safe and effective. Other therapeutic approaches such as gene therapy, gene editing, stop codon read through, and therapy with small molecules are under development. Newborn screening is now allowing the early identification of MPS I patients, who can then be treated within their first days of life, potentially leading to a dramatic change in the disease’s progression. Supportive care is very important to improve quality of life and might include several surgeries throughout the life course.

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

“…However, also observed by others, long term outcomes are poor and disease progression is evident in all [6,28,[34][35][36][37][38][39][40][41]. We confirm that the most common clinical manifestations pre-HSCT continue to worsen included hip dysplasia, kyphosis, valvular heart disease, hearing impairment and corneal clouding [42]. This longterm follow-up study, 32 years for the oldest patient, has allowed us to observe and report not only progression of disease but also the acquisition of other undocumented disease manifestations.…”

Dysostosis in mucopolysaccharidosis type 2: A case of longitudinal follow up and literature review

“…In the cardiovascular areas, in addition to the GAG deposition in tissues, MPS showed an abnormality in the turnover of collagen and elastin [15 , 16] and induced overexpression of cathepsin B in the fibroblasts of the heart, vascular wall, and valves, which can lead to degradation of collagen and elastin even in the extracellular matrix [30] . Although cardiovascular events could be fatal in MPS, enzyme replacement treatment with optimal administration might improve the prognosis [31 , 32] .…”

Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

“…MPS I was previously divided into three categories based on phenotype severity; that is, Hurler syndrome (OMIM 607014; the severe phenotype), Hurler–Scheie syndrome (OMIM 607015; the intermediate phenotype), and Scheie syndrome (OMIM 607016; the mild phenotype) [ 47 ]. Owing to overlapping symptoms in the three categories, MPS I is now categorized as severe, which includes Hurler syndrome, or attenuated, which includes Hurler–Scheie syndrome and Scheie syndrome [ 47 , 48 , 49 ]. The severe phenotype is most common, with a reported rate of 60.9% [ 47 ].…”

“…The severe phenotype is most common, with a reported rate of 60.9% [ 47 ]. Neurological impairment is present in the severe phenotype, but is often absent from the attenuated phenotype [ 48 ]. Symptoms common in both phenotypes include coarse facial features, corneal clouding, hepatomegaly, cardiac valve abnormalities, hernia, lumbar kyphosis (gibbus), hearing loss, upper airway infection, and sleep apnea [ 47 , 48 , 49 ].…”

“…Chronic otitis media is also common, with an estimated rate of 89.1% [ 22 ]. The conductive component is attributed to frequent otitis media, a thickened tympanic membrane, and ossicular chain abnormalities [ 21 , 23 , 24 , 48 ]. The sensorineural component is believed to develop later in life after conductive hearing loss is already present [ 50 ].…”