Attenuated mucopolysaccharidosis: are you missing this debilitating condition?

When rheumatologists think of mucopolysaccharidosis (MPS), if they think of it at all, it is likely they will think of a rare, inherited, chronic and progressive condition that affects young children. This is true for severe or fast progressing MPS, which is usually diagnosed by paediatric rheumatologists. There are, however, attenuated or slow-progressing forms that are less well known and patients with these conditions may present to the adult rheumatology clinic. The attenuated or slow-progressing form develops slowly and insidiously and is often not diagnosed until the patient is an adolescent or an adult. Crude incidence rates from Baehner et al. [1] suggest between 3.4 and 4.5 per 100 000 live births are affected by various types of MPS, meaning this condition is only occasionally seen in clinical practice. Indeed, data from Cimaz et al. [2] show that only 9% of rheumatologists and paediatric rheumatologists have ever seen a patient with MPS I, but an additional 13% thought that they might have a patient with MPS I in their care. These percentages are likely to be similar for the other types of MPS. Patients with the attenuated or slow-progressing form of MPS will often fail to initially receive a correct diagnosis of their condition and may present to a rheumatologist with bone and joint symptoms. As <20% of rheumatologists will consider MPS in the differential diagnosis, this condition may remain untreated [2], even though enzyme replacement therapy is available for some types of MPS. This delay in treatment can reduce the patient's quality of life, may mean they receive unnecessary medical therapy and ultimately shorten their life expectancy. MPS are a family of inborn metabolic conditions that are caused by the deficiency of one of the enzymes responsible for the degradation of glycosaminoglycans (GAGs). There are 11 known enzyme deficiencies that cause seven distinct types of MPS: namely I, II, III, IV, VI, VII and IX [1–4]. These enzyme deficiencies inhibit the catabolism of tGAGs, such as chondroitin, dermatan, heparan or keratan sulphate. Although it is accepted that MPS is a progressive disorder and the various types share many clinical features, the presenting symptoms vary depending on the enzyme affected and severity of the disease. The extent of symptoms and rate of progression will also vary between individuals affected by a specific type. Patients with severe or fast-progressing MPS are often diagnosed by paediatric rheumatologists. In contrast, diagnosing patients with …