INTRODUCTION
Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the N-acetylgalactosamine 4 sulfatase enzyme (also known as arylsulfatase B or ASB) which results in the accumulation of the glycosaminoglycan (GAG) dermatan sulfate (DS) in different tissues. [1] The disease is associated with high morbidity and reduced life expectancy, [2,3] although its incidence is lower than that of other MPS (1 / 455,000 live births).[4] In Monte Santo, Brazil, the prevalence is estimated at 20/1,000,000, probably as a result of a founding effect and inbreeding, with a single homozygous mutation present (p.H178L) [5] No studies reporting the prevalence of this disease are available in Peru or other Latin American countries.
The N-acetylgalactosamine 4 sulfatase enzyme is found predominantly in the skin, but also in tendons, blood vessels, airways and heart valves.[6] Studies have shown that DS accumulation creates an inflammatory response through the tumor necrosis factor (TNF) pathway, resulting in chondrocyte apoptosis and ensuing progressive arthropathy, [7, 8] affecting bone, cartilage, liver, spleen, ligaments, joints, heart valves, airways, meninges and corneas.
Clinical signs and symptoms are multisystemic and heterogenous as a result of DS accumulation in the different tissues. There is evidence of growth stunting, coarse facies, thick hair, skeletal deformities, frequent upper airway infections, hepatosplenomegaly, hearing loss, sleep apnea and stiff joints.[2] Also reported are other anatomical abnormalities and heart valve dysfunction in all patients. [3]
Patients with MPS VI generally appear healthy at birth, with symptoms usually manifesting in early infancy as a result of increased GAG concentration in the cells. The clinical presentation varies according to the age of onset and the rate of progression of the disease. Progression of MPS VI is categorized as classical or atypical, depending on the symptoms. [9 ] The highest urinary GAG levels are associated with rapidly progressing disease. [9]
ASB mutations have a genotype-phenotype correlation according to residual enzyme activity and are responsible for the heterogeneity of the clinical presentation. [10] The definitive diagnosis is made on the basis of deficient ASB enzyme activity confirmed in cultured fibroblasts or isolated leukocytes (value <10% the lower limit of normal) and/or demonstration of two mutations that cause the disease. [2,3,11] Elevated GAGs in the urine and high DS concentrations are markers of disease activity but, alone, are not diagnostic methods.
Patients with MPS VI require an interdisciplinary approach to the management of their disease. Enzyme replacement therapy (ERT) with galsulfase was approved in 2005-2006 in Europe, the United States, Brazil, Ecuador and Australia, among other countries. [12,13] This therapy slows down disease progression as it restores ASB enzymatic function, preventing GAG accumulation. [14] It is associated with improved functional endurance tests (6-minute and 12-minute walk test, and 3-minute stair climb), reduction in urinary GAG levels, stabilization of cardiac and pulmonary progression at 5-year follow-up, and reduced 10-year mortality. [13,15–17]
The objective of this study is to report the case of a patient in Peru with a diagnosis of MPS VI on ERT, focusing on the general characteristics of MPS VI, the course of the disease, and findings regarding the use of enzyme replacement therapy over a 6-year period.