Long-term outcome of patients with alpha-mannosidosis - A single center study

Mol Genet Metab Rep. 2021 Dec 9;30:100826. doi: 10.1016/j.ymgmr.2021.100826.

PMID: 35242565

Patryk Lipiński, Agnieszka Różdżyńska-Świątkowska, Katarzyna Iwanicka-Pronicka

Highlights: The aim of this study was to present the long-term follow-up of 12 Polish patients with alpha-mannosidosis (AM), evaluate the clinical, biochemical, and molecular findings and progression of the disease.

Abstract

Introduction: The full natural history of the uncommon autosomal recessive lysosomal storage disorder known as alpha-mannosidosis (AM) has not yet been described. This study's objectives included presenting the long-term follow-up of 12 Polish AM patients and assessing the clinical, biochemical, and molecular results and disease progression.

Material and methods: A long-term (over 30 years) observational, retrospective, single-center study of AM patients is presented in the publication.

Results: One of the initial symptoms, hearing loss, was found in 10 patients while they were children (mean age: 2 years, 6 months). Recurrent infections (present in all patients), inguinal hernias (6 patients), and craniosynostosis are among the additional symptoms (1 patient). The median age was four years, while the mean age at AM diagnosis was six years (age range: 1 year and 8 months - 12 years). The MAN2B1 gene's c.2245C > T, p.(Arg749Trp) variant was the one that was most frequently found. In this investigation, the mean follow-up period was about 14 years (range: 1 year - 26 years). Children with AM grow slowly after birth before finally achieving the third percentile (or values below the 3rd percentile). While intellectual disability was gradually worse in all patients without any developmental regression, hearing loss did not progress in this way. Six patients were found to have ataxia in their second decade of life (age range 15-20 years).

Conclusions: This research showed that sensorineural hearing loss, which was hereditary and did not worsen during the course of the disease, was one of the early symptoms of AM. Observation of the growth drop during the course of the extended follow-up allowed for the provision of a detailed anthropometric characterization of AM patients. This research supported the existence of two distinct clinical phenotypes for AM (mild and moderate), as well as the absence of a clear genotype-phenotype relationship.

Keywords: Congenital sensorineural hearing loss, Growth decline, Lysosomal storage disease, MAN2B1 gene, alpha-mannosidosis