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.

Keywords: Enzyme replacement therapy; Morquio A syndrome; Mucopolysaccharidosis IV A.

Fig. 1

3D structure of GALNS.

Fig. 2

Mutational spectrum of the GALNS gene. Aminoacids corresponding to the active site of the GALNS enzyme are marked as (*): p.Asp39, p.Asp40, p.Cys79/dihydroxy alanine, p.Arg83, p.Tyr108, p.Lys140,p.His142, p.His236, p.Asp288, p.Asn289, and p.Lys310. Taken from Amelia Morrone et al., 2014 and Rivera-Colon et al., 2012.

Fig. 3

Family pedigree showing four affected individuals and two index cases; two affected individuals with the same clinical phenotype died at 19 and 20 years of age.

Fig. 4

Body characteristics of the two cases showing disharmonic dwarfism with short trunk in relation to the lower limbs, overall shortening of the limbs with brachydactyly, bell-shaped chest, prominent sternum, kyphosis. Picture obtained after informed consent from the patients.

Fig. 5

Facial characteristics of the index case. Evidence of broad forehead, macrostomia, square jaw, flat nasal bridge and short neck. Picture obtained after informed consent from the patient.

Fig. 6

Spinal radiograph: evidence of deviation secondary to vertebral body deformities with shortened height and anterior wedging, odontoid hypoplasia and platyspondylia.

Fig. 7

Facial characteristics of the index case's sibling: There is evidence of prognatism, macrostomia, flat nasal bridge, corneal opacity and short neck. Picture obtained after informed consent from the patient.

Fig. 8

Chest x-ray with bilateral parahilar symmetrical reticular interstitial infiltrates; congestive pulmonary hilum, with solid nodular image in the left perilingular region and well-defined contours and edges; global cardiomegaly, widened costal arch deformities, and generalized abnormal bone tissue density (osteopenia).