Consensus ; Humans ; Mucopolysaccharidosis II/therapy*

Child, Preschool ; Humans ; Male ; Mucopolysaccharidosis II ; diagnosis ; genetics ; therapy ; Siblings

PURPOSE: The mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. They are caused by a deficiency of the enzymes involved in the degradation of glycosaminoglycans. Early recognition is important because recombinant enzyme replacement therapy is now available for MPS. We studied the clinical characteristics of 80 MPS children with the object of determining the epidemiological, clinical and radiological features in Korean MPS children. METHODS: Diagnosis of MPS was confirmed by skin fibroblast enzyme analysis in 80 patients between February 1995 and December 2004. Charts were retrospectively reviewed for clinical and radiological findings, as well as for intelligence and speech evaluations. RESULTS: Hunter syndrome (MPS type II) was the most prevalent type, appearing in 51/80 cases (64 %), followed by Sanfilippo syndrome (MPS III-18%), Hurler syndrome (MPS I-15%), and Morquio syndrome (MPS IV-4%). The average age at diagnosis was 5.5 years (range 1 to 20), and the male-to-female ratio was 4.7: 1. Typical radiographic changes were observed in 45/54 cases (83%). Mitral regurgitation was the most common cardiac defect. Moderate to profound mental retardation and hearing loss were present in 14/35 cases (56%) and 33/38 cases (82%), respectively. Four MPS II patients had bone marrow transplantation, with mixed outcomes. Five MPS I patients are currently on enzyme replacement therapy. CONCLUSION: Our study showed a high proportion of MPS II cases (64%), which may represent population variability. By studying the clinical features of these patients, we hope to alert pediatricians of the warning signs of MPS.
Bone Marrow Transplantation ; Child ; Diagnosis ; Enzyme Replacement Therapy ; Fibroblasts ; Glycosaminoglycans ; Hearing Loss ; Hope ; Humans ; Incidence ; Intellectual Disability ; Intelligence ; Korea ; Mitral Valve Insufficiency ; Mucopolysaccharidoses* ; Mucopolysaccharidosis I ; Mucopolysaccharidosis II ; Mucopolysaccharidosis III ; Mucopolysaccharidosis IV ; Retrospective Studies ; Skin

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase(R)) or idursulfase beta (Hunterase(R)) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.
Adolescent ; Body Height ; Child ; Child, Preschool ; Demography ; Enzyme Replacement Therapy ; Humans ; Iduronate Sulfatase/*therapeutic use ; Infant ; Male ; Mild Cognitive Impairment/etiology ; Mucopolysaccharidosis II/complications/diagnosis/*therapy ; Mutation ; Phenotype ; Protein Isoforms/therapeutic use ; Republic of Korea ; Young Adult

PURPOSE: Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT). MATERIALS AND METHODS: Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age. RESULTS: The mean glucose level after an 8-hour fast was 94.1 +/- 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4. CONCLUSION: Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes.
Animals ; Blood Glucose/analysis ; Enzyme Replacement Therapy/methods ; Glycogen/*analysis ; Glycosaminoglycans/*analysis ; Hepatocytes/chemistry/*enzymology ; Humans ; Hypoglycemia/enzymology/physiopathology ; Iduronate Sulfatase/genetics/*physiology ; Liver/ultrastructure ; Mice ; Mice, Knockout ; Microscopy, Electron ; Mucopolysaccharidosis II/blood/enzymology/physiopathology

BACKGROUND AND OBJECTIVE: Hunter syndrome(mucopolysaccharidosis (MPS) type II) is a genetic, metabolic disease of excessive mucopolysaccharide storage leading to mental and skeletal abnormalities, distinctive facial features, hearing loss, and airway problems. Its eventual lethal outcome results from cardiac failure and progressive obstruction of the airway. We tried to outline the otolaryngologic manifestations and management of patients based on the results of our study and review of the relevant literature. MATERIALS AND METHODS: Nine patients with Hunter syndrome were included in this study. Every patient was interviewed for the evaluation of any abnormality in the head and neck region, intelligence and language. Audio tests, temporal bone CT, and plain films of cervical spine were also performed. RESULTS: Upper airway obstruction occurred in most of patients, and necessitated tonsillectomy and adenoidectomy in 4 patients. Tracheal narrowing occurred in 3 patients. Otitis media with effusion, hearing loss and thickening of the external auditory canal and tympanic membrane were commonly observed in patients, and ventilation tubes were inserted in 4 patients. Mental retardation was more profound in the severe type Hunter syndrome, but speech function was disordered in both severe and mild type. CONCLUSION: Accurate evaluation and management of airway obstruction is needed to prevent lethal airway problems. Aggressive audio and otological managements, including the management of otitis media, hearing aids and speech therapy are required to enhance communicative development and improve their quality of life.
Adenoidectomy ; Airway Obstruction ; Ear Canal ; Head ; Hearing Aids ; Hearing Loss ; Heart Failure ; Humans ; Intellectual Disability ; Intelligence ; Metabolic Diseases ; Mucopolysaccharidosis II* ; Neck ; Otitis Media ; Otitis Media with Effusion ; Quality of Life ; Speech Therapy ; Spine ; Temporal Bone ; Tonsillectomy ; Tympanic Membrane ; Ventilation