Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series

Abstract

Background This case series includes longitudinal clinical data of ten patients with Morquio A syndrome from south and southeastern parts of Turkey, which were retrospectively collected from medical records. All patients received enzyme replacement therapy (ERT). Clinical data collected included physical appearance, anthropometric data, neurological and psychological examinations, cardiovascular evaluation, pulmonary function tests, eye and ear-nose-throat examinations, endurance in the 6-min walk test and/or 3-min stair climb test, joint range of motion, and skeletal investigations (X-rays, bone mineral density). Results At the time of ERT initiation, two patients were infants (1.8 and 2.1 years), five were children (3.4–7.1 years), and three were adults (16.5–39.5 years). Patients had up to 4 years follow-up. Most patients had classical Morquio A, based on genotypic and phenotypic data. Endurance was considerably reduced in all patients, but remained relatively stable or increased over time in most cases after treatment initiation. Length/height fell below normal growth curves, except in the two infants who started ERT at ≤ 2.1 years of age. All patients had skeletal and/or joint abnormalities when ERT was started. Follow-up data did not suggest improvements in skeletal abnormalities, except in one of the younger infants. Nine patients had corneal clouding, which resolved after treatment initiation in the two infants, but not in the other patients. Hepatomegaly was reported in seven patients and resolved with treatment in five of them. Other frequent findings at treatment initiation were coarse facial features (N = 9), hearing loss (N = 6), and cardiac abnormalities (N = 6). Cardiac disease deteriorated over time in three patients, but did not progress in the others. Conclusions Overall, this case series with Morquio A patients confirms clinical trial data showing long-term stabilization of endurance after treatment initiation across ages and suggest that very early initiation of ERT optimizes growth outcomes.

Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease

“…The enzyme, Elosulfase alfa, works within lysosomes to catabolize the glycosaminoglycans (GAGs) that have accumulated within. ERT has shown clinical improvement in somatic manifestations, activities of daily living, and quality of life ( 5 – 9 ). It has a low mortality risk with no limitations on use, however, the enzymes have a short half-life with rapid clearance from circulation resulting in poor delivery to bone and avascular tissues such as cartilage and cornea even when started at a young age.…”

Natural Evolution of Morquio: A Syndrome Caused by Two Heterozygous Mutations of the GALNS Gene

“…The incidence of Morquio A syndrome was estimated to be 1:201.000 and varied among different populations 2 . Treatment of Morquio A syndrome is possible with an enzyme-replacement therapy 3 ; however, this treatment was not available where the patient was residing. Natural evolution leads to a deleterious effect on growth and development.…”