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Lysosomal storage disorders for the pediatric rheumatologist: the example of mucopolysaccharydoses

The Mucopolysaccharidoses (MPS) are a group of diseases caused by complete or partial deficiency of lysosomal enzymes responsible for glycosaminoglycans catabolism. Their accumulation within the lysosome leads to cellular damage and organ failure [1, 2].

The musculoskeletal system is the most frequently affected one. Joint stiffness, contractures (claw hand), dysostosis multiplex, and carpal tunnel syndrome are some of the most frequent features [39]. Often the joint symptoms may be confused with inflammatory arthritides such as Juvenile Idiopathic Arthritis [10, 11]. A prompt differential diagnoses is a fundamental step: in MPS patients there are no signs of local inflammation such as swelling, warmth and tenderness, and lack of fever and increased inflammatory markers. In addition, patients with MPS do not respond to anti-rheumatic therapy [12, 13].

In addition, characteristic facies, cognitive impairment, short stature, recurrent otitis media, sleep apnea, hearing, vision and heart problems can be present [14, 15]. Because of a wide variety of clinical presentation, diagnosis of MPS disorders is often delayed, especially in patients with mild forms and without neurocognitive impairment such as Scheie Syndrome.

When clinical features are suggestive for MPS, the diagnosis is confirmed with the assay of urinary GAG concentration, which is a sensitive but not specific method [16] and, as the gold standard with determination of the specific enzyme in cultured fibroblasts, leukocytes, plasma or serum [17]. The genetic sequencing could be used to identify the disease-causing mutation.

The managment of MPS disorders requires a multidisciplinary evaluation for multi-organ involvement. The new therapeutic approaches to MPS have drastically changed the natural history of disease. Transplantation of hematopoietic stem cells from bone marrow or umbilical cord can achieve significant benefits. The clinical success of this therapeutic approach depends on age, stage of disease, type of donor and ability to achieve stable engraftment without the development of graft-vs-host disease [18, 20]. In early stages of disease, enzyme replacement therapy can benefit musculoskeletal symptoms and lung function [2123]. This therapy, however, does not cross the blood-brain barrier and has not shown neurocognitive benefit.

In conclusion, the goal is the prompt identification of MPS disorders since an early diagnosis could allow early treatment: in this regard, particular attention should be given to an accurate differential diagnosis with chronic inflammatory arthropathies.


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Correspondence to Rolando Cimaz.

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Cimaz, R., Mauro, A. Lysosomal storage disorders for the pediatric rheumatologist: the example of mucopolysaccharydoses. Ital J Pediatr 41 (Suppl 2), A17 (2015).

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