# Prenatal Diagnosis of c.437–1G>A Mutation in the MAN2B1 Gene in a Family With Alpha-Mannosidosis: Unraveling Clinical Presentation and Treatment Outcomes in a Novel Prenatal Case

## TL;DR

A family with alpha-mannosidosis successfully used prenatal diagnosis to identify the condition early and begin treatment before symptoms appeared.

## Contribution

This case report presents a novel prenatal diagnosis and early treatment approach for alpha-mannosidosis.

## Key findings

- Prenatal diagnosis of MAN2B1 c.437–1G>A mutation allowed early enzyme replacement therapy initiation.
- The patient showed mild skeletal involvement and normal development at the start of treatment.
- ERT levels increased to 15.8 µmol/l/h at 11 months of age with ongoing developmental monitoring.

## Abstract

Alpha-mannosidosis is a rare lysosomal storage disorder with progressive impairments in motor functions, skeletal deformities, and immunodeficiency. Enzyme replacement therapy (ERT) should be initiated early to achieve optimal outcomes. This report describes how alpha-mannosidosis diagnosis in a seven-year-old girl led to a successful prenatal diagnosis in the subsequent pregnancy and pre-symptomatic treatment at the early disease stage. The index patient was a seven-year-old girl who was referred with a confirmed diagnosis of alpha-mannosidosis based on the presence of homozygous c.437-1G>A mutation in the MAN2B1 gene. A prenatal diagnosis was made in the subsequent pregnancy through molecular analysis, which revealed the same homozygous variant. The patient was treated at the fifth week of age and showed mild skeletal involvement and normal development at ERT initiation. At 11 months of age, the ERT level increased to 15.8 µmol/l/h. The motor assessment showed that the patient was developmentally normal and was able to maintain her sitting and walking for a few steps only. Prenatal molecular screening in affected families can allow for the early identification and implementation of appropriate management strategies for alpha-mannosidosis.