Clinical outcomes in elderly patients with Morquio a syndrome receiving enzyme replacement therapy - experience in a Colombian center

Abstract

Introduction Mucopolysaccharidosis type IV A (MPS IVA) or Morquio A syndrome is an autosomal recessive lysosomal storage disease caused by GALNS gene mutations that lead to a deficiency of the N -acetylgalactosamine-6-sulfate sulfatase enzyme and the accumulation of two glycosaminoglycans in cell lysosomes, namely, chondroitin and keratan sulfate. Objective To present two female patients with Morquio A syndrome in their late adult years (over 50 years of age) with a classical phenotype, treated with enzyme replacement therapy; and to present a summary of the natural history and the characteristics of the disease, and the benefit of comprehensive management. Materials and methods Descriptive clinical study before and after the treatment with enzyme replacement therapy as part of the comprehensive management of MPS IVA. Results Enzyme replacement therapy with elosulfase alfa was effective, with an adequate safety profile in these two patients, showing evidence of sustained improvement in terms of endurance and gait patterns. Conclusion We present two cases of MPS IVA, with longer survival than reported previously in classical phenotypes associated with this disease condition. There is a paucity of reports of similar cases in the literature. We believe that the clinical heterogeneity of the disease manifesting with the classical phenotype, together with comprehensive management, have played a role in the survival of these two patients. Therapy with elosulfase alfa as part of comprehensive management has been crucial; we suspect a clinical response and infer a better quality of life and reduced burden for the caregiver, supporting its use in older patients.

Rare Case of Morquio Syndrome (Mucopolysaccharidosis Type IVA): Difficulties of Diagnostic Search and Management

“…Доказано, что под влиянием этой терапии снижается уровень кератансульфата в моче, улучшаются показатели в тестах с 6-минутной ходьбой и 3-минутным подъемом по лестнице, функциональные тесты легких, мышечный тонус и снижается уровень болевых ощущений у пациентов [11,14,15]. Есть данные, что проведение ферментозаместительной терапии даже в пожилом возрасте спустя 18 мес от ее старта приводило к увеличению подвижности суставов и двигательной активности в целом [16]. В случае ранней диагностики заболевания и старта лечения в первые годы жизни терапия более эффективна и мультисистемных необратимых поражений можно избежать.…”

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants

“…Two additional articles (L. Wang et al, 1999 ; Whybra et al, 2012 ), published before 2014, that were not included in the previous update were recovered by comparison of our list of variants with that reported by HGMD Professional 2020.1. Moreover, two other articles (Erazo‐Narváez et al, 2020 ; Ficicioglu et al, 2020 ) were recently published and, owing to the timing of the present article submission, were not included in the whole analysis. Ficicioglu et al ( 2020 ) reported three African American siblings who were compound heterozygotes for c.611A>G [p.(Asn204Thr)] and c.964G>C [p.(Ala322Pro)].…”

“…Ficicioglu et al ( 2020 ) reported three African American siblings who were compound heterozygotes for c.611A>G [p.(Asn204Thr)] and c.964G>C [p.(Ala322Pro)]. Erazo‐Narváez et al ( 2020 ) reported two Colombian women carrying the variants c.491A>C [p.(Asn164Thr)] and c.901G>T [p.(Gly301Cys)]. All of these variants had been previously described, with the exception of c.964G>C, which has been included in the present list of GALNS unique variants (Table S2 ).…”

Treating a teenager with Morquio A syndrome (mucopolysaccharidosis IV A) with Vimizim

“…В настоящее время к возрасту 18 лет пациент имеет рост 122 см, что соответствует средним показателям для больных с синдромом Моркио. Следует отметить, что даже в случае терапии элосульфазой альфа у пожилых пациентов через 18 мес они смогли восстановить способность к самостоятельному хождению, отмечали уменьшение боли и усталости [21]. Полученные данные указывают на положительное влияние ферментозаместительной терапии, подтверждают важность раннего начала лечения и необходимость его продолжения в течение всей жизни пациента [34].…”