• Journal of mucopolysaccharidosis and rare diseases
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• 제4권1호
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• pp.1-6
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• 2018

Lysosomal storage disorders are a group of rare inherited metabolic disorders with protean manifestations and variable severity ranging from attenuated forms to severe ones. It is necessary to diagnose and manage these disorders timely before irreversible damage occurs. Prior to the era of enzyme replacement therapy and newer therapeutics, only treatment option available was palliative care. Over the past two decades, extensive research in the lysosomal storage disorders has led to substantial expansion of our understanding about them. This mini review focusses on the spectrum, challenges faced in the diagnosis and therapy and remedial actions taken so far in lysosomal storage disorders in resource constrained country like India.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권1호
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• pp.17-18
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• 2016

Enzyme replacement therapy (ERT) is a well-established means of treating lysosomal storage disease (LSD). However, classical IV infusion based ERT method produces less than ideal results, especially, CNS defects and quality of life in patients. To improve these main problems of parental IV formulation for LSDs, we investigate modified ERT method and evaluated the efficacy in animal model.

• Journal of mucopolysaccharidosis and rare diseases
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• 제3권1호
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• pp.14-19
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• 2017

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes and subsequent accumulation of substrates. Enzyme deficiency leads to progressive intra-lysosomal accumulation of the incompletely degraded substances, which cause dysfunction and destruction of the cell and eventually multiple organ damage. Patients have a broad spectrum of clinical phenotypes which are generally not specific for some LSDs, leading to missed or delayed diagnosis. Due to the availability of treatment including enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation for some LSDs, early diagnosis is important. ERT products have been approved with optimal outcomes for some LSDs in the recent decades, including Gaucher, Fabry, mucopolysaccharidosis (MPS) I, Pompe, MPS VI, MPS II, and MPS IVA diseases. ERT can stabilize the clinical condition, prevent disease progression, and improve the long-term outcome of these diseases, especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods in the recent years, some LSDs, including Pompe, Fabry, Gaucher, MPS I, MPS II, and MPS VI diseases have been incorporated into nationwide newborn screening panels in Taiwan.

• 한국발생생물학회지:발생과생식
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• 제13권2호
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• pp.63-77
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• 2009

신경리포푸신증(NCLs)은 신경퇴행 축적 질환으로 뇌에 자기형광물질을 포함한 다양한 물질의 축적이 야기되어 발생하며, 노던에필렙시를 제외한 모든 신경포푸신증은 리소즘 축적 질환으로 분류된다. 이러한 신경리포푸신증은 전세계적으로 12,500명 중 1명에게 발생되는 높은 발병 빈도를 나타내며, 그 발병 시기에 따라 영아형, 영유아형, 유년형, 그리고 성인형과 같이 분류된다. 신경리포푸신증이 유발하는 의학적 증상로는 시각 손실, 발작, 간질, 진행성 정신지체등을 야기하여 소아성 치매라는 이야기를 들으며, 증상이 심할 경우 환자가 사망에 이르게 된다. 신경퇴행성 리포푸신증의 원인은 유전자의 돌연변이 때문이라고 알려져 있으며, 일부의 연구를 통해 태아의 발생과정 상 문제를 통해 질병이 야기되는 경우도 관찰이 되고 있으나, 아직 그 분자 발생학적 기전이 명확하게 규명되어 있지 않은 현실이다. 현재 전 세계적으로 많은 연구가 수행되고 있어 그 결과가 주목되는 바이다.

• 대한유전성대사질환학회지
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• 제23권1호
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• pp.1-11
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• 2023

Inborn errors of metabolism encompass a wide variety of disorders, frequently affecting bone. This review presents a comprehensive retrospect on the primary involvement of bone in inborn errors of metabolism. Primary involvement of bone in inborn errors of metabolism includes entities that primarily affect the bone marrow, mineral component or cartilage. These include lysosomal storage disorders, hypophosphatasia, and hereditary hypophosphatemic rickets. In this review, we discuss the primary involvement of bone in inborn errors of metabolism (hypophosphatasia, X-linked hypophosphatemic rickets, Gaucher disease, and mucopolysaccharidoses) along with the therapeutic agents used in clinical settings, diagnostic strategies, and general management. With the development of disease-specific targeted therapies and supportive care, more number of patients with these disorders live longer and survive into adulthood. Moreover, skeletal symptoms have become a more prominent feature of these disorders. This makes the awareness of these skeletal symptoms more important.

• Molecules and Cells
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• 제38권9호
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• pp.806-813
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• 2015

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

• 대한소아치과학회지
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• 제34권1호
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• pp.150-155
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• 2007

뮤코다당증(Mucopolysaccharidosis, MPS)은 glycosaminoglycans(GAGs)의 분해에 필요한 라이소좀 효소(lysosomal enzymes)의 결함으로 GAGs의 대사 산물이 세포의 라이소좀내에 축적되어 점차 세포와 조직, 기관의 기능 이상을 초래하고 신체 질환과 정신 발달 지연을 가져오는 질환이다. 본 증례는 심각한 치은 증식을 가진 뮤코다당증 환아를 전신 마취 하에 치은 절제술을 시행한 치험례이다. 소아치과 의사는 뮤코다당증 환아의 구강내 증상과 치과 치료시 주의 사항에 대해 숙지해야 하고, 내과의와 연계하여 환아의 전신 상태 변화에 민감하게 대처하여 치과 치료를 시행해야 한다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권1호
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• pp.1-6
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• 2021

Next-generation sequencing (NGS) technologies have changed the process of genetic diagnosis from a gene-by-gene approach to syndrome-based diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS). A priori information on the causative genes that might underlie a genetic condition is a prerequisite for genetic diagnosis before conducting clinical NGS tests. Theoretically, DPS, DES, and DGS do not require any information on specific candidate genes. Therefore, clinical NGS tests sometimes detect disease-related pathogenic variants in genes underlying different conditions from the initial diagnosis. These clinical NGS tests are expensive, but they can be a cost-effective approach for the rapid diagnosis of rare disorders with genetic heterogeneity, such as the glycogen storage disease, familial intrahepatic cholestasis, lysosomal storage disease, and primary immunodeficiency. In addition, DES or DGS may find novel genes that that were previously not linked to human diseases.

• Journal of Genetic Medicine
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• 제19권1호
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• pp.32-37
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• 2022

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase B due to mutations in the ARSB gene. Here, we report the case of a Korean female with a novel variant of MPS VI. A Korean female aged 5 years and 8 months, who is the only child of a healthy non-consanguineous Korean couple, presented at our hospital for severe short stature. She had a medical history of umbilical hernia and recurrent otitis media. Her symptoms included snoring and mouth breathing. Subtle dysmorphic features, including mild coarse face, joint contracture, hepatomegaly, and limited range of joint motion, were identified. Radiography revealed deformities, suggesting skeletal dysplasia. Growth hormone (GH) provocation tests revealed complete GH deficiency. Targeted exome sequencing revealed compound heterozygous mutations in the ARSB genes c.512G>A (p.Gly171Asp; a pathogenic variant inherited from her father) and c.1157C>T (p.Ser386Phe; a novel variant inherited from her mother in familial genetic testing). Quantitative tests revealed increased urine glycosaminoglycan (GAG) levels and decreased enzyme activity of arylsulfatase B. While on enzyme replacement therapy and GH therapy, her height increased drastically; her coarse face, joint contracture, snoring, and obstructive sleep apnea improved; urine GAG decreased; and left ventricular mass index was remarkably decreased. We report a novel variant-c.1157C>T (p.Ser386Phe)-of the ARSB gene in a patient with MPS VI; these findings will expand our knowledge of its clinical spectrum and molecular mechanisms.

• Clinical and Experimental Pediatrics
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• 제49권11호
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• pp.1152-1157
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• 2006

Inherited metabolic disease is rare disorders that show symptoms mainly in pediatric age and early treatment is important for preventing complications of the disease. Recent development in molecular and biochemical techniques help clinicians with proper diagnosis of patients, however, many of the disease still remain lack of effective therapeutic strategies. Better understanding on biochemical and molecular basis of pathogenesis of the disease combined with advanced medical care would provide new sight on the disease that can also improve the quality of life and long-term prognosis of patients. Traditionally, there are several modalities in the treatment of metabolic diseases depend on the biochemical basis of the disease such as diet restriction, removing or blocking the production of toxic metabolites, and stimulating residual enzyme activity. The inherited metabolic disease is not familiar for many clinicians because the diagnosis is troublesome, treatment is complicated and prognosis may not as good as expected in other diseases. Recently, new therapeutic regimens have been introduced that can significantly improve the medical care of patients with metabolic disease. Enzyme replacement therapy has showed promising efficacy for lysosomal storage disease, bone marrow transplantation is effective in some disease and gene therapy has been trying for different diseases. The new trials for treatment of the disease will give us promising insight on the disease and most clinicians should have more interest in medical progress of the metabolic disease.