Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Abstract

BackgroundMucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives.ResultsThe mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists’ evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs*44, p.Q121*, p.L209Wfs*4, p.T409R, and c.1461_1462insN[710].ConclusionThe age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients.

The mutational spectrum of Hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients

“…However, the clinical profiles of the MPS II patients (P1-P7) were in agreement with several studies described in the literature, and the clinical manifestations of the phenotype of Hunter syndrome ranged from moderate to severe Hunter syndrome phenotypes [13].…”

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report

“…Neurological degeneration was found in 23.3% of 77 South American MPS II patients, while Chiong et al. found that 91.3% of Filipino MPS II patients revealed development delay/mental disorders.…”

“…In the literature, behavior disorders such anxiety, hyperactivity, aggression, and sleep upset have been reported. 1,3 Neurological degeneration was found in 23.3% of 77 South American MPS II patients, 14 while Chiong et al 15 found that 91.3% of Filipino MPS II patients revealed development delay/mental disorders.…”

Evaluation of Demographic and Clinical Characteristics of Patients with Mucopolysaccharidosis

“…Reviewing different geographic regions showed us that MPS III and MPS I were detected frequently in Tunisia (14) while MPS VI was relatively more common in Egypt, different from the other countries (15). Australian studies revealed MPS III and MPS I (16) as the most common types; and MPS II was the most common type in the Philippines (17). As for the studies in our country, the most common types of MPS detected by several authors (18) (18,20).…”

“…Physical examination findings showed that the most commonly detected clinical findings were coarse facial appearance, skeletal findings, and hepatosplenomegaly. In the literature, published demographic studies involving different types of MPS reveal the most common clinical findings as follows: coarse face, corneal opacity, macroglossia in MPS I (21); short stature, joint stiffness, and coarse facial appearance in MPS II (17); growth retardation, coarse face, hepatosplenomegaly in MPS III (22); short stature, limited joint movement, pectus carinatum in MPS IV (23); coarse face, joint and skeletal abnormalities in MPS VI (24). In our study, since the number of patients with subtypes of MPS was limited, no differentiation based on subtype could be made.…”