Clinical overview and treatment options for non‐skeletal manifestations of mucopolysaccharidosis type IVA

Abstract

Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations, including short stature, skeletal dysplasia, cervical instability, and joint destruction, are known to be associated with this condition. Due to the severity of these skeletal manifestations, the non-skeletal manifestations are frequently overlooked despite their significant contribution to disease progression and impact on quality of life. This review provides detailed information regarding the non-skeletal manifestations and suggests long-term assessment guidelines. The visual, auditory, digestive, cardiovascular, and respiratory systems are addressed and overall quality of life as measured by endurance and other functional abilities is discussed. Impairments such as corneal clouding, astigmatism, glaucoma, hearing loss, hernias, hepatomegaly, dental abnormalities, cardiac valve thickening and regurgitation, obstructive sleep apnea, tracheomalacia, restrictive and obstructive respiratory compromise, and muscular weakness are discussed. Increased awareness of these non-skeletal features is needed to improve patient care.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-012-9459-0) contains supplementary material, which is available to authorized users.

Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double‐blind, pilot study

“…Most apparent are the musculoskeletal and joint issues, including short‐trunk dwarfism and chest, spine, hip, knee, and ankle abnormalities, atlantoaxial instability, and wrist hypermobility [Harmatz et al, 2013; Hendriksz et al, 2015a]. Common non‐skeletal manifestations include cardiorespiratory compromise, spinal cord compression, corneal clouding, hearing loss, hepatosplenomegaly, and dental abnormalities [Harmatz et al, 2013; Hendriksz et al, 2013; Hendriksz et al, 2015a]. Most patients with Morquio A syndrome show reduced endurance and/or mobility [Harmatz et al, 2013], which can be due to musculoskeletal abnormalities, joint pain, cardiorespiratory compromise, and/or neurological disease secondary to spinal cord compression.…”

Mortality in Patients with Morquio Syndrome A

“…Cardiac valve disease and respiratory complications leading to limitations in endurance are common in patients with Morquio syndrome A from late childhood (John et al 1990;Hendriksz et al 2013), and both are associated with disease involvement in multiple body systems (Hendriksz et al 2013). GAG accumulation in the upper airways and tonsils predisposes the patient to the development of obstructive sleep apnoea and upper airway obstruction (Walker et al 2003;Montaño et al 2007).…”

Spectrum of Skeletal and Non-Skeletal Manifestations of Morquio A Syndrome in an Adult: A Case Report

“…Corneal clouding, although common, is milder; astigmatism can occur, and reported cases of glaucoma have been open-angle as opposed to closed-angle as reported for other MPS disorders [24]. Dental abnormalities, including spaced dentition, pointed cusps, spade-shaped incisors, and enamel hypoplasia are also characteristic of MPS IVA [24].…”

“…Signs of respiratory compromise, such as limited endurance, frequent respiratory tract infections, sleep apnea, and snoring, are common in MPS IVA [24]. Other non-skeletal findings include mitral and/or aortic value regurgitation and thickening, conductive and sensorineural hearing loss, and muscle weakness [24] Visual impairment in MPS IVA differs slightly from other MPS disorders.…”