2 The condition

2 The condition

2.1 Mucopolysaccharidosis type IVa (also known as MPS IVa and Morquio A syndrome, and referred to in this document as MPS IVa) is an inherited lysosomal storage disease caused by a lack of the enzyme N‑acetylgalactosamine‑6‑sulfatase. The enzyme deficiency leads to accumulation of glycosaminoglycans, such as keratan sulphate, in the cells of several tissues and organs, causing progressive tissue damage.

2.2 MPS IVa causes a wide spectrum of symptoms that worsen over time, including respiratory disease, joint and skeletal abnormalities, hearing loss, corneal clouding and heart valve disease. MPS IVa also causes pain, fatigue, progressive loss of endurance and increasing dependence on a wheelchair. It leads to reduced life expectancy, primarily through respiratory failure and heart problems (63% and 15% of deaths respectively). The joint and skeletal abnormalities play a role in the development of respiratory symptoms but other factors, including upper and lower airway obstruction and reduced muscle strength from glycosaminoglycan deposition, can also have a significant effect on respiratory function. Some people have a particularly severe form of the disease, with early onset, high morbidity and rapid progression, although others have a more attenuated form. The signs and symptoms typically appear in early childhood, with more than 70% of people presenting before age 3 years. At the time of the evaluation, there were 88 people living with MPS IVa in England, and about 3 new diagnoses made per year. The company and patient group noted that 74–77 of these people were anticipated to be eligible for enzyme replacement therapy and may want treatment with elosulfase alfa.

2.3 Managing MPS IVa involves a multi‑disciplinary approach to treat the symptoms and address the complications; before elosulfase alfa became available, there were no treatments that address the underlying disease. Because of the rarity and heterogeneity of this condition, there is no standard treatment or pathway of care. Management may include surgery for skeletal problems, respiratory support, drugs to manage heart disease, dental and eye care, pain relief, and hearing aids and ventilating tubes to manage deafness and middle ear effusions. The lysosomal storage disorders expert group has developed a standard operating procedure for England to guide the management of this condition. Most people with MPS IVa are treated at 1 of 8 specialist centres (3 paediatric centres and 5 adult centres).