Mucopolysaccharidosis type I is a rare autosomal recessive disorder caused by deficiency of α-l-
iduronidase (IDUA) which leads to a wide spectrum of clinical severity. Here, we describe the case of four male patients who present the previously undescribed p.L18P mutation. Patient 1 (p.L18P/p.L18P) presents, despite multiple joint
contractures, an attenuated phenotype. Patient 2 (p.L18P/p.W402X) was diagnosed at 4 years of age with
bone dysplasia, coarse
facies, limited mobility, claw hands and underwent bilateral carpal tunnel surgery at 6 years of age. Patients 3 and 4 (both p.L18P/p.L18P) are brothers. Patient 3 was diagnosed at 4 years of age, when presented claw hands, lower limb and
shoulder pain, restricted articular movement and bilateral
carpal tunnel syndrome. Patient 4 was diagnosed at 17 months of age when presented lower limb
pain at night, respiratory
allergy and repeated upper airways
infections. Bioinformatics analysis indicates that p.L18P mutation reduces the
signal peptide to 25
amino acids and alters its secondary structure. In conclusion, we report a new IDUA variant that alters the structure of the
signal peptide, which likely impairs transport to lysosomes. Moreover, it leads to a distinct attenuated phenotype with mainly bone and cartilage symptoms, without visceromegalies,
heart disease, or
cognitive impairment.