Iranian Journal of Pathology

A Rare Compound Heterozygous NAGLU Gene Mutation in Two Siblings with Mucopolysaccharidosis type Iiib

Document Type : Case Reports

Authors

Laleh Vahedi-Larijani 1
Maryam Sotudeh Anvari 2
Alireza Biglari 3
Maryam Nabati 4
Hosna Banihashemi 5
Marzie Mohammadi Kharkeshi 6

1 Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Department of Molecular Pathology, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran

3 Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Cardiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Cardiovascular Research Center, Sari, Iran

5 Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

6 Mazandaran University of Medical Sciences, Pathology Research Center, Sari, Iran

https://doi.org/10.30699/ijp.2025.2055938.3426
Abstract
Background & Objective: Mucopolysaccharidosis (MPS) type III, or Sanfilippo syndrome, is an autosomal recessive lysosomal storage disorder caused by mutations in genes encoding enzymes responsible for glycosaminoglycan (GAG) degradation. This case report describes two siblings with MPS type IIIB who exhibit a rare compound heterozygous mutation in the NAGLU gene.
Case Presentation: A 7-year-old girl and her 4-year-old brother were referred for evaluation due to learning disabilities, aggressiveness, and coarse facial features. Enzyme assay using tandem mass spectrometry on dried blood spots in both siblings revealed absent N-acetyl-α-glucosaminidase activity.
Conclusion: Targeted sequencing confirmed the diagnosis, identifying two heterozygous mutations, an in-frame insertion and a missense mutation, in exon 3 of the NAGLU gene: c.214_237dup (p.Ala72_Gly79dup) and c.625A>C (p.Thr209Pro). This rare genetic finding in two siblings with Sanfilippo syndrome type B underscores the importance of precise mutation identification. Accurate characterization of defective gene variants may provide insights into potential targets for gene therapy in monogenic disorders.

Keywords

Genetic Diseases
Mucopolysaccharidosis Type IIIB
Inborn Errors of Metabolism
Glycosaminoglycan
Intellectual Disabilities

Subjects

Copyright © 2026. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license also allows users to adapt, remix, transform, and build upon the material for any purpose, including commercial use.

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Iranian Journal of Pathology
Volume 21, Issue 1
Winter 2026
Pages 128-135

  • Receive Date 05 May 2025
  • Revise Date 31 July 2025
  • Accept Date 11 October 2025

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