Unique medical issues in adult patients with mucopolysaccharidoses

Abstract

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.

The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls

“…Stem cell transplantation for severe MPS I and enzyme replacement therapies for MPS Types I, II, IVA, and VI are reducing overall disease burden and extending patient lifespans [13]. However, clinical observation, examination of registry data, and large case series indicate that a majority of surviving patients develop progressive cardiovascular disease despite treatment.…”

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS

“…The MPSs are characterized by a broad clinical spectrum, ranging from severe neonatal forms to attenuated forms diagnosed later on in adults [4]. Symptoms generally involve organomegaly, umbilical and inguinal hernias, hearing loss, macroglossia, coarse facial features as well as cardiac, respiratory, skeletal and cognitive impairments [5,6]. Enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplant (HSCT) are available for patients with MPS I, II, VI, and VII [6][7][8].…”

Cochlear Implantation via the Transmeatal Approach in an Adolescent with Hunter Syndrome—Type II Mucopolysaccharidosis

“…In childhood, conductive or mixed-type hearing loss caused by otitis media is common, but the relative incidence of pure SNHL increases with age [1,6]. Moreover, the medical issues of patients with MPS are changing due to early diagnosis and increase of life expectancy, multidisciplinary care, and the introduction of ERT and HSCT [5,10,11]. Today, MPS patients live long enough to develop hearing problems.…”

“…However, there are no reports of such venous malformation in patients with MPS. In general, patients with MPS II show cardiovascular problems [4,10,11]. GAG deposition in the coronary arteries triggers narrowing or occlusion and can even cause sudden death [14]; since GAGs are deposited at various sites in the entire body, patients with MPS may show involvement of other vessels.…”

“…A study reported that the median survival age of patients with MPS was approximately 13.4 years [10]; however, after the introduction of ERT and other modalities of multidisciplinary care, the life expectancy has increased. Based on these facts, the number of patients with MPS with progressive SNHL presenting at the otologist's office is expected to increase, in-cluding many of those in the relatively older age group.…”