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

The IDUA gene (MIM 252800) provides instructions for producing alpha‐L‐iduronidase, which is essential for the breakdown of large sugar molecules called glycosaminoglycans (GAGs). Mutations in the IDUA gene have been found to cause Mucopolysaccharidosis type I (MPS I) (MIM 607014). This leads to the accumulation of GAGs within lysosomes causing many different organs and tissues to be dysfunctional. Deleted IDUA gene has not been reported in the literature, which showed to be associated with a severe phenotype in our proband case. We report a child from a consanguineous family who presented with severe cardiogenic shock attributed to dilated cardiomyopathy. He was also found to have hepatosplenomegaly, joint stiffness, hearing loss, corneal hazing, facial dysmorphism, and dilation of brain ventricles. Lysosomal storage disease particularly MPS I was suspected though it is considered to be an early atypical presentation. The diagnosis was achieved via gene mutation analysis which showed homozygous IDUA deletion of exon 9′ to 3′ in combination with a severe deficiency of alpha‐L‐iduronidase enzyme. A variant in the form of IDUA gene deletion may indicate an early severe phenotypic presentation of MPS I. Establishment of the diagnosis permits genetic counseling, prevents patients from undergoing unhelpful diagnostic procedures, and allows for accurate prognosis.