MPS I: Early diagnosis, bone disease and treatment, where are we now?

Abstract

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by α‐L‐iduronidase deficiency. Patients present with a broad spectrum of disease severity ranging from the most severe phenotype (Hurler) with devastating neurocognitive decline, bone disease and early death to intermediate (Hurler‐Scheie) and more attenuated (Scheie) phenotypes, with a normal life expectancy. The most severely affected patients are preferably treated with hematopoietic stem cell transplantation, which halts the neurocognitive decline. Patients with more attenuated phenotypes are treated with enzyme replacement therapy. There are several challenges to be met in the treatment of MPS I patients. First, to optimize outcome, early recognition of the disease and clinical phenotype is needed to guide decisions on therapeutic strategies. Second, there is thus far no effective treatment available for MPS I bone disease. The pathophysiological mechanisms behind bone disease are largely unknown, limiting the development of effective therapeutic strategies. This article is a state of the art that comprehensively discusses three of the most urgent open issues in MPS I: early diagnosis of MPS I patients, pathophysiology of MPS I bone disease, and emerging therapeutic strategies for MPS I bone disease.

18‐year follow‐up of enzyme‐replacement therapy in two siblings with attenuated mucopolysaccharidosis I

“…It is well known that bone disease is one of the most incapacitating manifestations in MPS I patients (Kingma & Jonckheere, 2021). Although current therapeutic strategies significantly alter the disease course, there is no effective therapeutic strategy available for MPS I bone disease so far.…”

“…This is primarily due to the complex pathophysiological mechanism behind the bone disease, involving the interaction among different factors such as GAG, growth factors, inflammation, autophagy, elastogenesis, and bone remodeling enzymes. Nevertheless, emerging therapeutic strategies such as gene therapy and anti‐inflammatory therapy are under investigation and so far have produced promising results (Kingma & Jonckheere, 2021).…”

“…It is well known that bone disease is one of the most incapacitating manifestations in MPS I patients (Kingma & Jonckheere, 2021).…”

Mucopolysaccharidosis Type 1 among Children—Neuroradiological Perspective Based on Single Centre Experience and Literature Review

“…Among other clinical manifestations, the most characteristic ones include coarse facial features, a wide nasal bridge and a flattened midface that develop typically during the first year of life [ 13 ] along with a growth delay resulting in short stature [ 14 ]. Others include hepatosplenomegaly, umbilical and inguinal hernias, recurrent respiratory infections with chronic nasal discharge and frequent otitis media [ 15 ]. Development and growth peak during the first years of life, which are followed by the slowing down and evident decline further on [ 16 ].…”

“…An early diagnosis is crucial and known to improve outcomes for MPS patients by prompt treatment initiation with hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) [ 15 ]. Supplementary management is based on relieving symptoms and supporting patients functioning.…”