Mucopolysaccharidoses seen in adults in rheumatology

Abstract

Mucopolysaccharidoses are a group of rare lysosomal storage diseases including a great number of polymorph syndromes, each being related to a particular mutation responsible for a deficiency of glycosaminoglycan degrading enzymes, leading to an accumulation of glycosaminoglycans in tissues. Many of them are diagnosed in children or teenagers and have a severe prognosis because of organ failure, and are consequently usually not seen by the adult rheumatologist. However, some of them have a more progressive presentation, with musculoskeletal symptoms at the forefront and a lifespan that nearly reaches that of the general population. These milder forms are more likely to be diagnosed in adults, in patients who have suffered for years and sometimes even decades with unrecognized mucopolysaccharidosis. Indeed, they can sometimes mimic inflammatory rheumatic disorders, and therefore be misdiagnosed for a long time. Recognition and diagnosis of these attenuated forms can be a real challenge as they lead to moderate and/or nonspecific symptoms such as joint pain or stiffness. Hence, rheumatologists should know about them. Early diagnostic is essential since specific treatment, like enzyme replacement therapy, is now available for some subtypes and might, if given early, slow down the development of tissue damage, which is unfortunately irreversible. This article provides the opportunity to review the main clinical and radiographic features, the diagnostic strategy and the update of management, which should be multidisciplinary and led by an experienced physician in a reference centre. The contribution of the rheumatologist is important to ensure symptom control and prevent complications.

Growth impairment and limited range of joint motion in children should raise suspicion of an attenuated form of mucopolysaccharidosis: expert opinion

“…The primary cause of chronic joint stiffness, limiting range of joint mobility (ROM) in patients with MPS (I, II, VI, and VII), and ligamentous laxity, responsible for joint hypermobility in MPS IV, is the involvement of GAG in the ligaments and capsule around the joint [ 28 , 52 ]. All joints are affected but with varying rates of progression which ultimately result in degenerative joint disease if left untreated [ 27 ].…”

“…We have noted that children with MPS complain minimally of pain: as such, diminished abduction and anteflexion in the shoulder (an indicator of stiffness) and flexion deformity of the elbow are often overlooked. Stiffness of the knees and ankles as well as knee and ankle flexion deformities inhibits the heel–sole–toe stance (the plantigrade foot) and can have a significant impact on gait and the ability to walk independently [ 27 , 31 ].…”

“…In practice, differential diagnoses are numerous, and AMPS are misdiagnosed as rheumatic fever or as atypical inflammatory rheumatoid arthritis (juvenile inflammatory arthritis if early onset), psoriatic arthritis, etc. [ 27 , 31 ]. However, limited range of joint mobility, even moderate, in the absence of clinical or biological inflammation is signs of pathology (especially among children) and should raise suspicions of an MPS disorder [ 1 , 7 , 25 ].…”

How Not to Miss the Mild Forms of Mucopolysaccharidosis Type I in Patients With Articular Manifestations of the Disease?

“…В настоящий момент выделяют 7 типов МПС (I, II, III, IV, VI, VII, IX). При этом самая высокая заболеваемость среди этой группы принадлежит МПС I (0,69-1,66 на 100 000 новорожденных) и IIIa типов (0,29-1,89) [7].…”

Mucopolysaccharidosis Type I, Hematopoietic Cell Transplantation and Neurodevelopmental Profile: A Case Report

“…Partially degraded glycosaminoglycans accumulate in lysosomes resulting in progressive cell dysfunction that translates into multiorgan failure. 1 Mucopolysaccharidosis are classified as types I to IX and each one represents a specific enzymatic deficit, phenotypic variability and distinct clinical and imaging characteristics. 2 Type I mucopolysaccharidosis is caused by an alpha-L-iduronidase deficit and has three phenotypic expressions, according to the residual activity of the enzyme and consequent severity of the condition: Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome.…”