Mucopolisacaridosis: características clínicas, diagnóstico y de manejo

Abstract

The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at lysosomal level. When there is a deficiency of a particular enzyme there is an accumulation of GAGs in the cells resulting in progressive cellular damage, which can affect multiple organ systems and lead to organ failure. Diagnosis is based on knowledge of the clinical manifestations, performing biochemical analyses to identify the type of GAG that is accumulating, and confirm the type of disorder with the corresponding enzymatic determination. Their identification is essential to initiate early treatment, taking into account that multidisciplinary management and enzyme replacement therapy is available for MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), and MPS VI (Maroteaux-Lamy syndrome. In this review, an analysis is made of each of these syndromes, as well as their diagnosis and treatment.

Otorhinolaryngological Findings in Patients from Southwestern Colombia with Clinical, Enzymatic and Molecular Diagnosis of Mucopolysaccharidosis II, IV-A and VI

“…Different researches around the world have reported levels of hearing loss in patients with MPS, demonstrating that when this condition occurs it is usually mixed, which includes diversity of conditions at the same time in the same patient. In general, hearing loss is usually attributed to problems associated with OM and eustachian tube dysfunction [25]; In addition, there has been talk of the loss of sensorineural hearing of unknown etiology, possibly due to the accumulation of GAGs, in the cochlear duct, cochlear nerve and vascular stria [4], which prevents its efficient functioning. Specifically, in Colombia there were no studies associated with hearing loss in patients with MPS, in this ways the problems associated with OM were found in 47.8% of the patients evaluated, which represents a considerable figure for this condition.…”

“…Mucopolysaccharidosis (MPS) forms a group of inherited metabolic disorders caused by the specific deficiency of a hydrolase responsible for a step in the degradation of mucopolysaccharides or glycosaminoglycans (GAG) due to mutations in the genes that code for the enzymes involved in said degradation [1]; actually, four main GAGs are known: chondroitin sulfate, dermatan sulfate, heparan sulfate and keratin sulfate with variable localization in the body [2,3]; and its accumulation within the connective tissue results in a wide range and variety of clinical effects that depends specifically on the enzyme deficiency. [4] Thus, based on this enzyme deficiency, 7 different forms of MPS have been assigned: MPS I (Hurler's syndrome) [5] MPS II (Hunter's syndrome) [6] MPS III (Sanfilippo's syndrome) [7] MPS IV (Morquio syndrome) [8] MPS VI (Maroteaux-Lamy syndrome) [9], MPS VII (Sly disease) [10] and MPS IX (Natowicz syndrome) [11]; Each of these syndromes has a subtype and in total eleven enzymatic defects have been detected. All MPS are inherited as an autosomal recessive trait except Hunter syndrome (MPS II) which is a disease linked to the X chromosome [12].…”

“…Many of the adult patients with MPS IV exhibit permanent or severe hearing loss [20], and finally, although MPS VI is characterized by normal intellectual development with normal hearing in early infancy, it is important to examine for hearing loss, especially when an infant with this disease shows developmental delay. [21] For the patients affected with this disease, enzyme replacement therapy (ERT) has been implemented, which consists in supplying the patient with the exogenous protein that is being abnormally synthesized in their organism [4]; This therapy has been shown to be effective in decreasing the excretion of urinary GAGs, improving performance on the walk test and increasing forced vital capacity. In addition, organomegaly decreases, left ventricular hypertrophy and improves the range of joint mobility.…”

A selective screening program for the early detection of mucopolysaccharidosis

“…Scientific advances have led to a steady increase in the treatments available for MPS. [20,36–39] In fact, 5 of the 8 patients diagnosed in our series have already begun to receive ERT following international standards, and the other 3 are involved in phase I/II clinical trials.…”

“…[19] Given the progressive nature of MPS, early diagnosis and treatment is crucial. [20] Although some lysosomal storage disorders (LSDs) are now considered candidates for newborn screening programs, many challenges remain, such as the identification of late-onset phenotypes. [21] As a result, very few newborn screening programmes around the world include LSDs.…”