Mucopolysaccharidosis (MPS) are lysosomal disorders belonging to the inborn errors of metabolism. MPS are caused by a deficiency in one of the enzymes responsible for the degradation of glycosaminoglycans (GAGs), such as chondroitin-, dermatan-, heparan- or keratansulphate. Storage of GAGs in almost all tissues leads to a progressive multisystemic disease. Eleven enzyme deficiencies induce 7 types of mucopolysaccharidosis: MPS I, II, III, IV, VI, VII and IX. Various types share many clinical features, the presenting symptoms and severity of disease vary depending on the enzyme affected and the extent of symptoms and rate of progression will also vary between individuals. The estimated incidence is 1:25.000 live births.
This condition is usually diagnosed in children, it is often not considered during the differential diagnosis in adults. Patients with 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 less than 20% of rheumatologists will consider MPS in the differential diagnosis, this condition may remain untreated even though enzyme replacement therapy is available for some types of MPS. There is often a lack of mental impairment in some types of MPS disease, which may be viewed by some as a key feature of disease. In addition, a diagnosis of the slow-progressing form can be more problematic as this condition is often mistaken for other diseases. Fist symptoms include recurrent upper airway infection, cardiological involvement and skeletal deformities. Later in the course of slow-progressing MPS (and while undiagnosed), patients will often be seen by rheumatologists because of pain and stiffness in the joints, contractures, and hip and back pain. Surgery for hip dysplasia is commonly reported. The similarity of slow-progressing MPS to more commonly seen rheumatological conditions means that patients are often misdiagnosed or that there is a delay before the patient’s symptoms are attribute to MPS. Furthermore the typical facial phenotype, prior referred to as “gargoylism”, is no conditio sine qua non in slow progressing disease course of MPS. Joint disease in the absence of inflammation is a cardinal feature of slow-progressing MPS and this should raise the suspicion of this condition as a possible diagnosis.
Often urinary GAG measurement is the first diagnostic step for pediatric patients, but this assay may fail to diagnose MPS in adults who tend to have an age-related decline in GAG. Diagnosis can be confirmed by measurement of the enzyme activity in blood. Enzyme replacement therapy is available for MPS I, II and VI and is under investigation in a phase III trial for MPS IVA. At present specific treatment is not available for MPS III, VII and IX and as such patients receive supportive care. If untreated, MPS affects the skeletal system, heart, eyes, ears and lungs. Compression of the spinal cord at the craniocervical junction is a common and life-threatening feature. Treatment is partly able to prevent these organs from being irreversibly damaged as well as slowing disease progression and helping the patient to maintain their quality of life. If treatment is not available, or if the slow-progressing form remains undiagnosed, then the disease will progress and the patient may die at a younger age.
Aim is to raise awareness of this debilitating condition and lead to better management of patients with this debilitating condition.
Disclosure of Interest C. Lampe Grant/Research support from: Biomarin, Consultant for: Bioamrin, Shire
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