• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.7-11
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• 2002

Isovaleric acidemia is an inborn error in metabolism due to a defect in isovaleryl-CoA dehydrogenase. Accumulation of serum isovaleric acid causes poor feeding, vomiting, lethargy, hypothermia, convulsion, mental retardation, etc. It is inherited as an autosomal recessive trait. Since the first reports of isovaleric acidemia by Tanaka et al in 1966, more than 60 cases have been reported. There are two clinically different presentations of isovaleric acidemia, with about half the patients presenting with an acute severe neonatal form and about half with a chronic intermittent form. The difference in clinical presentation may not be a consequence of differing severities of the causative mutation, but a result of the timing of application of catabolic stress or the ability to form isovalerylglycine. We described here clinical and organic acid analytical findings of in 3 cases isovaleric acidemia.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.11 no.1
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• pp.52-73
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• 2011

Since we have started organic acid analysis on Jul. 1997, we have been collecting data about organic acidemias in Korea. The data presented here is our 3 years experience in organic acid analysis. We have collected 712 samples from major university hospitals all over the Korea, large enough for relatively accurate incidence of organic acid disorders. We are using solvent extraction method with ethylacetate, MSTFA for derivatization and quantitation of 83 organic acids simultaneously. Out of 712 patients sample, 498 patients sample (70%) showed no evidence of organic acid abnormalities. Out of 214 remaining samples we have found very diverse disorders such as methylmalonic aciduria(6), propionic aciduria (10), biotinidase deficiency (6), maple syrup urine disease (3), isovaleric aciduria (4), tyrosinemia type II (4), tyrosinemia type IV (1), glutaric aciduria type I (1), glutaric aciduria type II (22), 3-methylglutaconic aciduria type I (3), 3-methylglutaconic aciduria type III (7), HMG-CoA lyase deficiency (1), hyperglyceroluria (2), cytosolic 3-ketothiolase deficiency (55), mitochondrial 3-ketothiolase deficiency (3), 3-hydroxyisobutyric aciduria (2), L-2-hydroxyglutaric aciduria (2), fumaric aciduria (2), lactic aciduria with combined elevation of pyruvate (most likely PDHC deficiency) (28), lactic aciduria without combined elevation of pyruvate (most likely mitochondrial respiratory chain disorders) (35), SCAD deficiency (3), MCAD deficiency (1), 3-methylcrotonylglycineuria (1), orotic aciduria (most likely urea cycle disorders) (7) and 2-methylbranched chain acyl-CoA dehydrogenase deficiency (1). In conclusion, though the incidence of indivisual organic acidemia is low, the incidence of overall organic acidemia is relatively high in Korea. Most of the patients showed some signs of neurological dysfunction. In other words, organic acid analysis should be included in the diagnostic work up of all neurological dysfunctions.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.6-14
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• 2006

Propionic acidemia is an autosomal recessive metabolic disorder caused by a defect of propionyl CoA carboxylase with resultant accumulation of toxic organic acid metabolites. This disorder is biochemically characterized by metabolic acidosis, ketoacidosis, hyperglycinemia and hyperammonemia. Clinical symptoms are very heterogeneous and present as a severe neonatal-onset or a late-onet form. We describe one case of propionic acidemia in a 4-year-old boy who has developed gait disturbance after acute metabolic decompensation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.1
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• pp.54-56
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• 2013

Propionic acidemia is an inherited organic acid metabolic disorder. During chronic recurrent metabolic crisis, multiple blood transfusions can cause secondary hemochromatosis. We report a patient with propionic acidemia who had iron overload that resulted in liver dysfunction, cardiomyopathy and diabetes. When multiple blood transfusions are unavoidable, use of chelating agents for iron can prevent complications such as diabetes and hemochromatosis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.42-46
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• 2016

Isovaleric acidemia is autosomal-recessively inherited and an inborn error of metabolism caused by abnormal leucine metabolism due to the genetic defect of IVD (Isovaleryl-CoA dehydrogenase). IVD corresponds to mitochondrial matrix enzyme that acts on converting isovaleryl-CoA into 3-methylcrotonyl-CoA in the leucine catabolism. The IVD gene is located at Chromosome 15q14-q15, particularly between base pair 40,405,485 and base pair 40,435,948. It consists of 12 exons and has been reported to cause over 50 diseases so far. We conducted IVD gene test on the patient with acute isovaleric acidemia and confirmed a new type of mutation for the first time. As a result of analyzing the IVD gene sequence, we found out that c.129T>G(p.Asn43Lys) and c.1033A>G(p.Asn345Asp) mutations exist as heterozygosity at Exon 1 and Exon 10 respectively, novel mutation.

• Journal of Genetic Medicine
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• v.14 no.2
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• pp.80-85
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• 2017

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder characterized by an abnormal accumulation of methylmalonyl-CoA and methylmalonate in body fluids without hyperhomocysteinemia. Cardiac disease is a rarely known lethal complication of MMA, herein, we report a Korean neonate diagnosed with MMA on the basis of biochemical and genetic findings, who developed cardiomyopathy, resulting in sudden death. The patient presented vomiting and lethargy at 3 days of age. Initially, the patient had an increased plasma propionylcarnitine/acetylcarnitine concentration ratio of 0.49 in a tandem mass spectrometry analysis and an elevated ammonia level of $537{\mu}mol/L$. Urine organic acid analysis showed increased excretion of methylmalonate. Subsequent sequence analysis of the methylmalonyl-CoA mutase (MUT) gene revealed compound heterozygous mutations c.323G>A (p.Arg108His) in exon 1 and c.1033_1034del (p. Leu345Serfs*15) in exon 4, the latter being a novel mutation. In summary, this is the first case of MMA and cardiomyopathy in Korea that was confirmed by genetic analysis to involve a novel MUT mutation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.1
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• pp.61-64
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• 2017

Recurrent acute pancreatic attacks is a rare clinical condition (2-5% of all acute pancreatis) in children and is mainly idiopathic in most cases. Sometimes it may be associated with congenital anomalies, metabolic diseases or hereditary conditions. Isovaleric acidemia (IVA) is a rare autosomal recessive amino acid metabolism disorder associated with isovaleryl coenzyme A dehydrogenase deficiency presenting the clinical findings such metabolic acidosis with increased anion gap, hyperammonemia, ketonemia, hypoglycemia, "the odor of sweaty feet," abdominal pain, vomiting, feeding intolerance, shock and coma. Recurrent acute pancreatitis associated with IVA have been rarely reported. Herein; we report a child who admitted with recurrent acute pancreatic attacks and had the final diagnosis of IVA. Mutation analysis revealed a novel homozygous mutation of (p.E117K [c.349G>A]) in the IVA gene. Organic acidemias must kept in mind in the differential diagnosis of recurrent acute pancreatic attacks in children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.2
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• pp.249-255
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• 2001

Methylmalonic acidemia is a rare congenital autosomal recessive metabolic disease. It is caused by blocking in the pathways of isoleucine, valine, threonine, methionine, cholesterol and odd-chain fatty acids to succinyl CoA, resulting in the increase of L-methylmalonyl CoA and methylmalonic acid. In most cases, there are symptoms such as recurrent vomitings, lethargy and laboratory abnormalities including metabolic acidosis and hyperammonemia from the neonatal period. We had a 6-month-old infant with methylmalonyl acidemia who presented with recurrent vomiting episodes since 3 months of age, failure to thrive and developmental delay. The laboratory findings showed hyperammoninemia and ketotic metabolic acidosis. Plasma amino acid analysis showed nonspecific finding. Urine organic acid ananysis by gas chromatography and mass spectrometry detected large amount of methylmalonic acid excreted in the urine. We restrained the supply of protein in the amount of 1~1.5 g/kg of body weight a day using leucine, isoleucine and valine-r-estrained milk and administered vitamine $B_{12}$, in the amount of 1mg per day. During the follow-up in the outpatient clinic, He could control his head and showed increased muscle strength.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.1
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• pp.13-17
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• 2018

Methylmalonic acidemia is an autosomal recessive disorder caused by complete (mut0) or partial (mut-) deficiency of methylmalonyl-CoA mutase (MUT) or by defects in the synthesis of adenosylcobalamin (cblA, cblB, cblD variant 2). Long term complications of methylmalonic acidemia include tubulointerstitial nephritis with progressive renal failure, intellectual impairment, pancreatitis, and growth failure. We report a case of methylmalonic acidemia in a girl who diagnosed at 6 days after birth. She has developed recurrent metabolic crises with hyperammonemia and metabolic acidosis. In addition, she suffered from the chronic complications including tubulointerstitial nephritis, electrolyte imbalance associated with renal dysfunction, growth failure and fracture of femur shaft. At the age of 10 years, hypercalcemia and severe osteoporosis were noted, and pamidronate therapy was given for two years, which relieved hypercalcemia and osteoporosis.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.258-267
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• 2006

Purpose : We have done this retrospective study to know the relative incidence and clinical manifestations of organic acidopathies in Korea during 8 years(from Jul. 1997 to May 2005). This results of organic acid analysis of 1,787 patients were compared with the results of organic acid analysis that were published three years ago. Methods : The results of quantitative organic acid analysis of samples of 1788 patients, referred from Jul. 1997 to May 2005, were analyzed retrospectively according to four age group(-2 mon, 3 mon-2 years, 3-12 years) and major clinical manifestations. Quantification of 83 organic acids was done with gas chromatography and mass spectometry. Results : We diagnosed 470 patients with 27 diseases of organic acid metabolism during this study period. Diseases found more than 10 cases are cytosolic 3-ketothiolase deficiency, mitochondrial respiratory chain disorders, PDHC deficiency, mitochondrial 3-ketothiolase deficiency, glutaric aciduria type II, biotinidase deficiency, methylmalonic aciduria and propionic aciduria. Other diseases were diagnosed in less than 10 cases. Conclusion : Though the incidence of individual organic acidemia is low, the overall incidence of organic acidemia as a whole seems to be relatively high in Korea. Compared with the results of organic acid analysis that were reported three years ago, we couldn't find a new disease and the difference of the relative incidences of high incident diseases. We were apprehensive of the errors that was owing to the short study period(3 years), but the relative incidences of our study(8 years) were similar to the results of organic acid analysis that were reported three years ago.