Maroteaux-Lamy syndrome is an autosomal recessive disease caused by deficiency of the lysosomal enzyme n-acetylgalactosamine 4-sulfatase (aryl-sulfatase B) which is involved in glycosaminoglycan (GAG) degradation [1,2]. Progressive accumulation of dermatan sulfate in nearly all tissues is believed to provoke the clinical symptoms associated with MPS VI. GAGs are an endotoxin like molecule that incites an inflammatory response via a tumour necrosis factor pathway and promotes apoptotic cell death of chondrocytes.
The estimated birth prevalence is 1 in 320,000 live births in Europe. There is no current worldwide incidence rate, and numbers may range according to country or specific ethnic populations studied. There are between 50 and 300 patients in the USA and approximately 1,100 patients in the developed world with MPS VI. Rapidly progressive forms usually present before two years of age with severe dysostosis multiplex and coarse facial features. Without proper treatment patients succumb before the 2nd or 3rd decade. A more slowly progressive (attenuated) form has been described with later onset, clinical symptoms in fewer systems, less pronounced dysostosis multiplex and longer survival [3,4].
Typically, adult height in the severe phenotype is less than 120 cm and dysmorphic appearance includes coarse facial features, frontal bossing, depressed nasal bridge, enlarged tongue and gingival hypertrophy. Other deformities like thoracic deformities (pectus carinatum), scoliosis or kyphosis (gibbus), macrocepahly, hepatosplenomegaly, protruding abdomen, inguinal and umbilical hernias. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex (in x-ray short thickened metacarpals, abnormal vertebral bodies, paddle shaped ribs and short thick clavicles), and degenerative joint disease. Oral, pharyngeal and upper airway obstruction is common. Both obstructive and restrictive respiratory disease is often present. Obstructive disease is related to bronchial narrowing and tracheobronchomalacia whereas restrictive disease is due to the small stiff thoracic cage and abdominal distension combined with kyphosis, scoliosis, and lumbar lordosis .
Cardiac involvement is frequent and an important cause of morbidity and mortality. The primary cardiac manifestation of MPS VI is progressive valve degeneration with stenosis and/or incompetence. Azevedo et al. reported mitral valve regurgitation (96%), tricuspid regurgitation (71%) and aortic regurgitation (43%) in 28 patients with MPS VI. Abnormal electrocardiograms (ECGs) occur in ¾ of all patients with sinus tachycardia and right and left axis deviation most common . Heart failure may emerge due to cardiomyopathy, fibroelastosis, valvular involvement, and pulmonary hypertension. Although coronary artery disease has been described only for MPS 1 its presence should be considered in MPS I, II, VI, VII patients.
Intellect is normal but significant learning issues may arise from hearing and visual limitation. Common neurological manifestations include carpal tunnel syndrome, spinal cord or nerve root compression, optic nerve injury, jugular foramen stenosis and communicating hydrocephalus. Spinal cord compression (SCC) is the result of spinal canal stenosis due to small thickened posterior elements, odontoid dysplasia, thickening of the dura, ligamentum flavum and cruciate ligaments, disk bulging or any combination of these. Stenosis can be exacerbated by the presence of flexion extension instability or gibbous deformity. Patients with MPS VI frequently experience myelopathy associated with SCC during childhood. Patients with SCC in rapidly progressive MPS VI require decompression surgery at a median age of 12 years whereas those with slowly progressive disease did not require surgery until 24 years of age [6,7].
Visual impairment is common (40% of MPS VI). Corneal opacification of varying severity (38% severe opacification) is frequently seen as well as refractive errors, glaucoma, retinopathy and optic nerve swelling and ocular hypertension .
Intravenous enzyme replacement therapy (ERT) by galsulfase (Naglazyme®) may improve certain somatic symptoms but not alleviate neurological symptoms. The enzyme does not reach poorly vascularised sites such as corneas and joint cartilage [9, 10, 11]. Bone marrow or haematopoietic stem cell transplantation (HSCT) has been used in rare cases to treat MPS VI patients [12, 13, 14, 15, 16, 17, 18, 19].