Genotype-Phenotype Correlations and Shifting Diagnosis Age in Turkish Mucopolysaccharidosis Type II Patients: A...

Background/Objectives: Mucopolysaccharidosis type II (MPS II) is an inherited metabolic disorder characterized by progressive neurologic and extra-neurologic findings. We aimed to explore the age at symptom onset and at diagnosis as well as contribute to the phenotype-genotype association with new observations of MPS II based on a broad series of patients in Turkey. Methods: The presented study was retrospective and descriptive. Data on molecular analysis results, the age of onset and diagnosis, diagnostic delays, neurologic and extra-neurologic symptoms, enzyme and urine glycosaminoglycan (GAG) level results, brain magnetic resonance imaging, echocardiography, and electromyography were reviewed. Results: A total of 46 MPS II patients from 40 families were involved. The mean diagnosis age was 40.1 ± 46.8 months, and the diagnostic delay was 19.7 ± 40.4 months. While the mean age of diagnosis of the first cases in the families was 45 ± 24 months, the mean age of diagnosis of the second cases was 14 ± 15 months. The mean age at diagnosis was 42 ± 18 months in the patient group born before 2010, while it was 28 ± 22 months in the patient group born in 2010 and after. The last measurement of the height SDS value showed a significant difference (p = 0.004) between the groups that started ERT before the age of three and those who began ERT at the age of three and above. Five patients showed an attenuated phenotype without neurologic involvement. The sequencing of the IDS gene revealed 25 distinct variants, with 8 novel variants that have yet to be documented in the existing literature. Conclusions: The findings from the observations of this Turkish MPS II cohort emphasize that the actual prevalence of MPS II is probably underestimated and that it has a broad spectrum of clinical phenotypes, even without neurological impairment. In children, specific warning signs-including a coarse facial appearance, abdominal distension, speech delays, and macrocephaly-should raise suspicion and prevent delays in diagnosis. Conducting urine GAG and enzyme analyses is crucial for cases with clinical suspicion. Our data showed that the age of diagnosis tended to decrease over the years.