The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report

Am J Med Genet A 2021 Nov;185(11):3510-3516. doi: 10.1002/ajmg.a.62469. Epub 2021 Sep 2.

PMID: 34472180

Marta Frigeni, David F Rodriguez-Buritica, Heather Saavedra

Highlights: The findings of this study indicate the need for novel treatment methods that target the skeletal system in affected patients.

Abstract

Background: Mucopolysaccharidosis type IVA (OMIM 253000) is an autosomal recessive condition caused by N-acetylgalactosamine 6-sulfatase (GALNS) enzyme dysfunction. For affected patients, enzyme replacement therapy (ERT) with recombinant human GALNS became available in 2014. To present, only a few research have looked at the effects of ERT in children, and there is also a scarcity of evidence on the effects of ERT in systems other than the skeleton.

Objectives: Here, we present the effect of ERT in two cases: Patient A, who is presently 4 years old and began therapy at the age of 5 months, and Patient B, who is currently 3 years old and began treatment at the age of 58 days, are the youngest siblings treated to date. We also look at the impact of early ERT on the cardiovascular system.

Results: Our findings suggest that even when ERT is initiated before the age of two months, it is unable to totally prevent disease progression. In terms of the effect of ERT on the cardiovascular system, preliminary findings show that early therapy may help afflicted individuals maintain a normal left ventricular mass index for at least up to a year, but further research is needed.

Conclusions: Overall, this study reveals that early diagnosis is still critical, and that early ERT has a limited effect in delaying the skeletal phenotype's progression, indicating the need for novel treatment methods that target the skeletal system in affected patients.

Keywords: MPS, Morquio A syndrome, Mucopolysaccharidosis type IVA, elosulfase alfa, enzyme replacement therapy, long-term management