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.