Difficulties in diagnosing slowly progressive mucopolysaccharidosis VI: A case series.
ABSTRACT An Erratum for this article can be found here: http://iospress.metapress.com/content/e16437020701m0u5/?p=df8dd6709cf44367a0c0e5d917aaeddf&pi=11We describe the cases of two adult sisters recently diagnosed with the attenuated form of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). MPS VI is a rare, clinically heterogeneous lysosomal storage disorder that is characterized by a deficiency in the glycosaminoglycan-degrading enzyme arylsulfatase B. Both cases had been misdiagnosed for over 30 years despite the presence of several characteristics of the disease, including short stature (mild), coarse facial features, skeletal dysmorphisms, carpal tunnel syndrome, heart valve disease, and spinal cord compression, which together are suggestive of a lysosomal storage disease. Awareness about the clinical features of MPS VI should be communicated amongst treating neurologists, rheumatologists and other specialists who are involved in the healthcare decisions of these patients with presenting symptoms, so they can refer them to specialized centers for proper diagnosis and treatment.
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ABSTRACT: Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI, OMIM 253200) is caused by mutations in the gene coding for N-acetylgalactosamine-4-sulfatase (4-sulfatase, arylsulfatase B, ARSB, EC 220.127.116.11), a lysosomal enzyme involved in the degradation of dermatan sulfate (DS). The clinical presentation of MPS VI varies greatly with respect to age of onset and rate of disease progression. This report focuses on the attenuated form of MPS VI, which can go unrecognized for years and often presents with atypical signs or symptoms. We described a cohort of MPS VI patients (n = 4) heterozygous for the p.Y210C mutation who had a significant osteoarticular involvement at the onset of their disease and who were diagnosed years or even decades later. We have also reviewed the literature (n = 36). Two types of attenuated MPS VI phenotypes could be distinguished: osteoarticular and cardiac. The majority of MPS VI patients reported so far as relatively attenuated presented with an essentially osteoarticular phenotype associated with the p.Y210C mutation. Patients homozygous for the p.R152W mutation presented with a cardiac phenotype, which, despite fulfilling the generally used criteria for attenuated phenotype, may lead to fast disease progression and abrupt death. The knowledge of natural history and genotype-phenotype correlation may help in developing a tailored therapy potentially using enzyme replacement therapy with substrate reduction therapy or chaperones.Clinical Rheumatology 11/2013; 33(5). DOI:10.1007/s10067-013-2423-z · 1.77 Impact Factor
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ABSTRACT: To describe cardiac abnormalities in patients with mucopolysaccharidosis (MPS) VI and to evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. Data from electrocardiographic and echocardiographic evaluations were retrospectively collected from patients with MPS VI who are followed up at the Children's Hospital of Mainz. The study included 44 (16 male and 28 female) patients. At baseline, valvular regurgitation (mainly aortic and mitral) and left ventricular (LV) volume overload were present in over half of patients. Other common cardiac manifestations were sinus tachycardia, LV hypertrophy, concentric LV remodelling, and pulmonary hypertension. One patient had left atrial dilation and one had congestive heart failure. Interventricular septal wall thickness and LV posterior wall thickness were above normal in most patients. Twenty five patients had a pre-ERT and at least one follow-up visit after ERT start. Mean follow-up after ERT start was 5.6 (SD 2.3) years. Despite the late onset (mean age 14.6 years) of treatment, ERT appeared to improve or arrest the progression of LV remodelling and LV hypertrophy and suspend the progression of cardiac valve disease. MPS VI is associated with an array of cardiac manifestations. ERT appears to have some impact on cardiac structure and function when started late in life, but may have better long-term results when started during early infancy.Journal of Inherited Metabolic Disease 09/2013; 37(2). DOI:10.1007/s10545-013-9649-4 · 4.14 Impact Factor
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ABSTRACT: Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI. This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias. An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex. Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis.Skeletal Radiology 01/2014; 43(3). DOI:10.1007/s00256-013-1797-y · 1.74 Impact Factor