• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.1-4
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• 2016

Mucolipidosis type II (MLII; MIM#252500) and type III alpha/beta (MLIIIA; MIM#252600) very rare lysosomal storage disease cause by reduced enzyme activity of GlcNAc-1-phosphotransferase. ML II is caused by a total or near total loss of GlcNAc-1-phosphotransferase activity whether enzymatic activity in patient with ML IIIA is reduced. While ML II and ML III share similar clinical features, including skeletal abnormalities, ML II is the more severe in terms of phenotype. ML III is a much milder disorder, being characterized by latter onset of clinical symptoms and slower progressive course. GlcNAc-1-phosphotransferase is encoded by two genes, GNPTAB and GNPTG, mutations in GNPTAB give rise to ML II or ML IIIA. To date, more than 100 different GNPTAB mutations have been reported, causing either ML II or ML IIIA. Despite development of new diagnostic approach and understanding of disease mechanism, there is no specific treatment available for patients with ML II and ML IIIA yet, only supportive and symptomatic treatment is indicated.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.23-24
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• 2002

저자들은 조악한 얼굴과 관절의 구축 등 Hurler 증후군과 유사한 임상 증상을 보이면서 혈장에서 리소좀 효소 활성도의 증가를 보였던 Mucolipidosis 2례를 경험하였기에 보고하는 바이다.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.8-12
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• 2016

Mucolipidosis (ML) is a kind of skeletal dysplasia. Characteristic X-ray findings of the bone may contribute to the early diagnosis and treatment of ML II/III. Skeletal radiographs show distinctive patterns at different ages: neonatal hyperparathyroidism, osteodystrophy (similar to chronic osteitis fibrosa cystica), and dysostosis multiplex. Patients with ML II/III show a mixture of osteodystrophic bone changes and atypical changes of dysostosis multiplex: proximal pointing of the metacarpals in the wrist, dysplastic changes in the lower third of the ilia, marked broadening of the ribs becoming oar-shaped, and beaking of the lower thoracic and lumbar vertebrae. In ML II, the osteodystrophy has clinical and radiographic features of neonatal hyperparathyroidism. In some neonatal subjects, chemical hyperparathyroidism is also demonstrated. After transient hyperparathyroidism in newborns, the progressive osteitis fibrosa cystica develops from 3-6 months of age. Patients with ML III show prominent skeletal involvement, particularly the destruction of vertebral bodies and the femoral heads. Intravenous pamidronate treatment is well tolerated, and it can produce clinical effects, with a reduction in bone pain and improvements in mobility in patients with ML III. In this review, the skeletal manifestations of ML II and III are investigated.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.31-31
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• 2016

Purpose: To describle clinical features and enzyme activity of Vietnamese patients with Mucolipidosis type II. Methods: Clinical features, laboratory and plasma lysosom enzyme activity by 4 MU-Fluorometric assay was studied from 2014-2015 at the Northern referral center of Pediatrics - National Children's Hospital. Results: 16 cases (7 girls and 9 boys) were diagnosed with I-cell bases on clinical symptoms and enzyme activities studies. Diagnosis age was $5.93{\pm}4.28$ years, onset age was recognised from birth to 4 years (median 1.25) with the feature of joint stiffness and bone deformation. All cases presented with the feature of joint stiffness, chest deformation and kyphoscoliosis; Fifteen cases (93.7%) had coarse facial features. No patients had hepatosplenomegaly on abdominal ultrasound, 5/15 patients had heart valves disease. Enzyme assay showed ${\alpha}$-Hexosaminidase of $1,885.9{\pm}338.7$ (nmol/mg plasma/17 hrs), ${\alpha}$-Iduronate sulfatase of $4,534.8{\pm}1,062.9nmol/mg$ plasma/4 hrs). Conclusion: Mucolipidosis II seriously affected the life of the patients with skeletal deformities, contractures develop in all joints and cardiac involvement.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.13-16
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• 2016

Mucolipidosis (ML) II/III are autosomal recessive diseases caused by deficiency of post-translational modification of lysosomal enzymes. The mannose-6-phosphate (M6P) residue in lysosomal enzymes synthesized by N-acetylglucosamine 1-phosphotransferase (GlcNAc-phosphotransferase) serves as recognition marker for trafficking in lysosomes. GlcNAc-phosphotransferase is encoded by GNPTAB and GNPTG. Mutations in GNPTAB cause severe ML II alpha/beta and the attenuated ML III alpha/beta. Whereas mutations in GNPTG cause the ML III gamma, the attenuated type of ML III variant. For the diagnostic approaches, increased urinary oligosaccharides excretion could be a screening test in clinically suspicious patients. To confirm the diagnosis, instead of measuring the activity of GlcNAc phosphotransferase, measuring the enzymatic activities of different lysosomal hydrolases are useful for diagnosis. The activities of several lysosomal hydrolases are decreased in fibroblasts but increased in serum of the patients. In addition, the sequence analysis of causative gene is warranted. Therefore, the confirmatory diagnosis requires a combination of clinical evaluation, biochemical and molecular genetic testing. ML II/III show complex disease manifestations with lysosomal storage as the prime cellular defect that initiates consequential organic dysfunctions. As there are no specific therapy for ML to date, understanding the molecular pathogenesis can contribute to develop new therapeutic approaches ultimately.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.65-75
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• 2005

Purpose: To understand genetic differences and similarities between mucolipidosis and control. Methods: Using the fibroblast of the mucolipidosis II and control, forward and reverse subtracted libraries were constructed. Among these clones, we investigated mutations in the GNPTA (MGC4170) gene, which codes for the ${\alpha}/{\beta}$ subunits of phosphotransferase, and in the GNPTAG gene, which codes for the ${\gamma}$ subunits in 5 Korean patients with mucolipidosis type II or IIIA. Result: Several differentially expressed cDNAs were cloned and their sequences were determined. Mutation analysis of the interested gene, GNPTA was performed and we identified 7 mutations in the GNPTA gene, but none in the GNPTAG gene. The mutations in type II patients included p.Q104X(c.310C>T), p.R1189X(c.3565C>T), p.S1058X(c.3173C>G), p.W894X(c.2681G>A) and p.H1158fsX15(c.3474_3475delTA), all of which are non-sense or frame shift mutations. However, a splicing site mutation, IVS13+1G>A (c.2715+1G>A) was detected along with a non-sense or a frame shift mutation (p.R1189X or p.E858fsX3(c.2574_2575delGA)) in two mucolipidosis type IIIA patients. Conclusion: This report shows that mutations in the GNPTA gene coding for the ${\alpha}{\beta}$subunits of phosphotransferase, and not mutations in the GNPTAG gene, account for most of mutations found in Korean patients with mucolipidosis type II or IIIA.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.99-106
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• 2018

Mucolipidosis type III (pseudo-Hurler polydystrophy) is a mucolipids degrading disorder caused by a mutation in the GNPTAB gene and is inherited by autosomal recessive. It is diagnosed by examining highly concentrated mucolipids in blood and the diagnosis can be confirmed by genetic testing. Mucolipidosis type III is a rare and progressive metabolic disorder. Its initial signs and symptoms usually occur around 3 years of age. Clinical manifestations of the disease include slow growth, joint stiffness, arthralgia, skeletal abnormalities, heart valve abnormalities, recurrent respiratory infection, distinctive facial features, and mild intellectual disability. Here, we are presenting two siblings of mucolipidosis type III, a 4-year-old female and a 2 years and 7 months old male with features of delayed growth and coarse face. The diagnosis was confirmed by [c.2715+1G>A(p.Glu906Leufs*4), c.2544del(p.Glu849Lysfs*22)] mutation in targeted gene panel sequencing. In this case, c.2544del is a heterozygote newly identified mutation in mucolipidosis type III and was not found in the control group including the genome aggregation database. And it is interpreted as a pathogenic variant considering the association with phenotype. Here, we report a Korean mucolipidosis type III patients with novel mutations in GNPTAB gene who have been treated since early childhood. Owing to recent development of molecular genetic techniques, it was possible to make early diagnosis and treatment with pamidronate was initiated appropriately in case 1. In addition to these supportive therapies, efforts must be made to develop fundamental treatment for patients with early diagnosis of mucolipidosis.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.28-28
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• 2016

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.29-30
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• 2016

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.19-22
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• 2016

Purpose: Mucolipidosis type II (ML II), also known as I-cell disease is an autosomal recessive inherited disorder of lysosomal enzyme transport caused by a deficiency of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase). Clinical manifestations are skeletal abnormalities, mental retardation, cardiac disease, and respiratory complications. A severely and rapidity progressive clinical course leads to death before 10 years of age. Methods/Results: In this study we diagnosed three cases of prenatal ML II in two different at-risk families. We compared two procedures -biochemical analysis and molecular analysis - for the prenatal diagnosis of ML II. Both methods require an invasive procedure to obtain specimens for the diagnosis. Biochemical analysis requires obtaining cell cultures from amniotic fluid for more than two weeks, and would result in a late diagnosis at 19 to 22 weeks of gestation. Molecular genetic testing by direct sequence analysis is usually possible when mutations are confirmed in the proband. Molecular analysis has an advantage in that it can be performed during the first-trimester. Conclusion: Molecular diagnosis is a preferable method when a prompt decision is necessary.