Molecular Basis, Diagnosis and Clinical Management of Mucopolysaccharidoses

Abstract

Mucopolysaccharidoses (MPSs) are a group of hereditary, monogenic disorders caused by lysosomal storage of glycosaminoglycans. Their incidence as a group is between 1:25,000 and 1:45,000. At present 11 different enzyme deficiencies are know to be responsible of 7 similar but distinct diseases. The diagnosis is suspected clinically but must be confirmed through biochemical, enzymatic and molecular analysis. Prenatal diagnosis is feasible for each disease. The phenotype worsens with age, due to progressive storage, and mainly involves mucosal tissue, upper airways and lungs, bones and joints, central and peripheral nervous system, heart, liver, eye and ear. Any type of MPSs, is characterized by a wide variability of phenotype ranging from a severe fetal-neonatal disease to an attenuated form diagnosed in adult individuals. Recently new treatments, like hematopoietic stem cell transplantation and enzymatic replacement therapy, became available for many of these disorders entailing the urgency of early diagnosis to allow access to therapies. Thanks to therapies these patients have a longer life than in the past and this implies that also palliative treatments, of which the cardiological ones have a prominent part, must be undertaken diligently. The cardiologist may face, more frequently than expected, with the need to diagnose a patient with MPS who was not recognized by other specialists. The echocardiographic features of these patients are typical and may help in the clinical diagnosis. The future probably deserves to these disorders other new treatments or combination therapies, which might further improve prognosis of these diseases

Damages of Cardiovascular System at Mucopolysaccharidosis Type I: Clinical Cases

“…Вместе с тем R. Parini и соавт. [4], а также P. Russo и соавт. [5] показали, что даже своевременная ФЗТ не вызывает регрессии изменений клапанов сердца.…”

“…Накопление частично деградированных ГАГ приводит к утолщению и дисфункции клапанов сердца, гипертрофии миокарда, нарушению проводимости, поражению коронарных артерий и других сосудов [1]. Поражение клапанов сердца является наиболее частой (у 60-90% пациентов) формой патологии сердечно-сосудистой системы при МПС [4][5][6]. Стеноз и недостаточность клапанов могут стать причиной перегрузки, дилатации и гипертрофии левых отделов сердца и, как следствие, развития систолической и диастолической сердечной недостаточности [1,6,7].…”

Clinical hints to diagnosis of attenuated forms of Mucopolysaccharidoses

“…Valvulopathy is the main cardiac sign in MPS individuals with slowly progressing disease. The mitral and aortic valves are the most commonly affected, irrespective of the type of MPS, with valve thickening and regurgitation, followed by stenosis [ 16 , 17 ].…”

“…Cardio-surgery is a good option to treat these complications but, as with other surgical procedures, the risk of adverse events during or immediately after surgery increases in MPS patients [ 17 ] (see Moretto et al in this Supplement [ 18 ]). Rehabilitation may be difficult in the presence of orthopedic issues.…”

Diagnosis and Management of Lysosomal Storage Disorders. Three Key Words: Early, Multidisciplinary, and Network

“…The cardiologist is one of the specialists involved in LSD management. Indeed, myocardial involvement (cardiomyopathy) is a typical feature of Pompe disease and AFD, while valvular degeneration is typically present in patients with mucopolysaccharidoses 6 and, sometimes, in patients with Gaucher disease. 7 Early diagnosis is one of the key points for an efficacious ERT, and this is a fundamental message for any specialist involved in the management of these disorders.…”