• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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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.

• Journal of Microbiology and Biotechnology
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• v.23 no.5
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• pp.689-698
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• 2013

The production and characterization of an active recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21(DE3) has been previously reported. In this study, the effect of the signal peptide (SP), inducer concentration, process scale, and operational mode (batch and semi-continuous) on GALNS production were evaluated. When native SP was presented, higher enzyme activity levels were observed in both soluble and inclusion bodies fractions, and its removal had a significant impact on enzyme activation. At shake scale, the optimal IPTG concentrations were 0.5 and 1.5 mM for the strains with and without SP, respectively, whereas at bench scale, the highest enzyme activities were observed with 1.5 mM IPTG for both strains. Noteworthy, enzyme activity in the culture media was only detected when SP was presented and the culture was carried out under semi-continuous mode. We showed for the first time that the mechanism that in prokaryotes recognizes the SP to mediate sulfatase activation can also recognize a eukaryotic SP, favoring the activation of the enzyme, and could also favor the secretion of the recombinant protein. These results offer significant information for scaling-up the production of human sulfatases in E. coli.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.46-52
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• 2022

Inborn errors of metabolism (IEM) are very rare and genetically transmitted diseases and have man y different symptoms related with multisystemic involvement. More rarely, endocrinopathies can be an early and first symptom of IEM, but presents with signs of later complications in adolescent or adulthood. The mechanisms of endocrine dysfunction in IEM are poorly understood. Hypogonadotropic hypogonadism is common in hemochromatosis, adrenoleukodystrophy, galactosemia, and glycogen storage disease. Many girls with classic galactosemia are at high risk for premature ovarian insufficiency (POI), despite an early diagnosis and good control. Mitochondrial diseases are multisystem disorders and are characterized by hypo- and hypergonadotrophic hypogonadism, thyroid dysfunction and insulin dysregulation. Glycogen storage disorders (GSDs), especially type Ia, Ib, III, V are assocciated with frequent hypoglycemic events. IEM is a growing field and is not yet well recognized despite its consequences for growth, bone metabolism and fertility. For this reason, clinicians should be aware of these diagnoses and potential endocrine dysfunction.

• Clinical and Experimental Pediatrics
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• v.62 no.2
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• pp.43-47
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• 2019

Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.1-6
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• 2021

Among the various etiologies of cardiomyopathy, inborn errors of metabolism (IEM) is one of the underlying causes, especially in the pediatric population. The accurate identification of the IEM of cardiomyopathy may lead to better prognosis through disease-specific management. Therefore, clinicians should always keep in mind the possibility that IEM may be one of the underlying etiologies of cardiomyopathy, and carry out multi-systematic clinical approach to diagnosis of IEM. This review covers the pathophysiology, clinical presentations, typical laboratory findings, diagnosis, and proper treatment of each type of IEM-induced cardiomyopathy in pediatric patients to gain a deeper understanding of this subject.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.6
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• pp.518-527
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• 2021

Purpose: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. Methods: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. Results: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. Conclusion: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.19-28
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• 2014

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.5
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• pp.411-422
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• 2020

With the increasing number of children with inflammatory bowel disease (IBD), very early-onset IBD (VEO-IBD), defined as IBD that is diagnosed or that develops before 6 years of age, has become a field of innovation among pediatric gastroenterologists. Advances in genetic testing have enabled the diagnosis of IBD caused by gene mutations, also known as monogenic or Mendelian disorder-associated IBD (MD-IBD), with approximately 60 causative genes reported to date. The diagnosis of VEO-IBD requires endoscopic and histological evaluations. However, satisfactory small bowel imaging studies may not be feasible in this small population. Both genetic and immunological approaches are necessary for the diagnosis of MD-IBD, which can differ among countries according to the available resources. As a result of the use of targeted gene panels covered by the national health insurance and the nationwide research project investigating inborn errors of immunity, an efficient approach for the diagnosis of MD-IBD has been developed in Japan. Proper management of VEO-IBD by pediatric gastroenterologists constitutes a challenge. Some MD-IBDs can be curable by allogenic hematopoietic stem cell transplantation. With an understanding of the affected gene functions, targeted therapies are being developed. Social and psychological support systems for both children and their families should also be provided to improve their quality of life. Multidisciplinary team care would contribute to early diagnosis, proper therapeutic interventions, and improved quality of life in patients and their families.

• Clinical and Experimental Pediatrics
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• v.58 no.4
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• pp.117-122
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• 2015

Global developmental delay (GDD) is a relatively common early-onset chronic neurological condition, which may have prenatal, perinatal, postnatal, or undetermined causes. Family history, physical and neurological examinations, and detailed history of environmental risk factors might suggest a specific disease. However, diagnostic laboratory tests, brain imaging, and other evidence-based evaluations are necessary in most cases to elucidate the causes. Diagnosis of GDD has recently improved because of remarkable advances in genetic technology, but this is an exhaustive and expensive evaluation that may not lead to therapeutic benefits in the majority of GDD patients. Inborn metabolic errors are one of the main targets for the treatment of GDD, although only a small proportion of GDD patients have this type of error. Nevertheless, diagnosis is often challenging because the phenotypes of many genetic or metabolic diseases often overlap, and their clinical spectra are much broader than currently known. Appropriate and cost-effective strategies including up-to-date information for the early identification of the "treatable" causes of GDD are needed for the development of well-timed therapeutic applications with the potential to improve neurodevelopmental outcomes.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.2
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• pp.75-80
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• 2013

Specific genetic conditions may lead to sudden unexpected deaths in infancy, such as inborn errors of fatty acid oxidation and genetic disorders of cardiac ion channels. The disease may present dramatically with severe hypoketotic hypoglycemia, Reye syndrome or sudden death, typically with a peak of frequency around 3-6 month, whilst neonatal sudden death is quite rare. When undetected, approximately 20-25% of infants will die or suffer permanent neurologic impairment as a consequence of the first acute metabolic decompensation. Meanwhile, the advent of newborn screening for metabolic diseases has revealed populations of patients with disorders of fatty acid oxidation (FAO), the most frequent of which is medium chain acyl-CoA dehydrogenase (MCAD) deficiency. Without this screening, affected individuals would likely succumb to sudden infant death syndrome (SIDS). Here we describe an overview of sudden infant death syndrome and inherited metabolic disorder.