Alpha-L-iduronidase deficiency: A novel mutation resulting in severe early presentation of Mucopolysaccharidosis type I and literature review of the molecular basis

Clin Case Rep. 2022 May 27;10(5):e05904. doi: 10.1002/ccr3.5904.

PMID: 35664514

Nuha Nasser Al Zaabi, Muneera Sirajum, Mohd Zaki Al-Wawi

Highlights: A variant in the form of IDUA gene deletion may indicate an early severe phenotypic presentation of Mucopolysaccharidosis type I (MPS I).

Abstract

Background: Large sugar molecules known as glycosaminoglycans must be broken down, and the IDUA gene (MIM 252800) supplies instructions for manufacturing alpha-L-iduronidase (GAGs). Mucopolysaccharidosis type I (MPS I) is caused by mutations in the IDUA gene (MIM 607014). This results in the accumulation of GAGs within lysosomes, which causes malfunction in a variety of organs and tissues. Unreported in the literature, the deleted IDUA gene in our proband case was associated with a severe phenotype.

Objective and findings: This article describe a child from a consanguineous family who had severe cardiogenic shock caused by dilated cardiomyopathy. Hepatosplenomegaly, joint stiffness, hearing loss, corneal hazing, facial dysmorphism, and dilation of brain ventricles were also discovered. Despite being regarded as an early atypical manifestation, MPS I was hypothesized to be a kind of lysosomal storage disease. The diagnosis was made via gene mutation analysis, which revealed a homozygous deletion of exons 9' to 3' in the IDUA gene coupled with a severe alpha-L-iduronidase enzyme deficiency.

Conclusion: An early severe phenotypic presentation of MPS I may be indicated by a variant in the form of IDUA gene deletion. Once the diagnosis has been made, patients can receive genetic counseling, are spared from unnecessary diagnostic procedures, and can receive an accurate prognosis.

Keywords: MPS, cardiovascular disorders, endocrinology and metabolic disorders, gastroenterology and hepatology, genetics, neurology