• Journal of The Korean Society of Inherited Metabolic disease
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• v.3 no.1
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• pp.32-37
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• 2003

Ornithine transcarbamylase(OTC) deficiency is the most common of all the urea cycle disorders. In this X-linked disorder, the hemizygote males are more severely affected than heterozygote females. The Heterozygote female may have mild episodic hyperammonemia symptoms in late infancy or childhood(late onset) or no clinical manifestations. Here we report a 6 year-old girl with late onset OTC deficiency who showed recurrent episodic lethargy, mental confusion and ataxia. On mutation analysis using DNA sequencing after PCR amplification of the 10 exons of OTC gene, G to T transversion in codon 221, causing substitution of asparagine for lysine was detected in exon 6.

• Journal of The Korean Society of Integrative Medicine
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• v.9 no.2
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• pp.105-108
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• 2021

Background : Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare, autosomal recessive metabolic disorder which is caused by genetic mutations that disrupt the urea cycle. It is characterized by variable clinical presentation and the age of onset. Patients may present with gait disturbance and progressive paraplegia and muscle tightness in the lower extremities. The use of botulinum toxin in metabolic disease has rarely been discussed. We describe a case of a 14-year-old-boy with HHH syndrome, who presented with a several - month history of gait disturbance and lower extremity weakness. Case presentation : A 14-year old male had a history of recurrent upper respiratory tract infections, occasional vomiting, loss of appetite, and general weakness, all of which started since he was 10 months old. He was diagnosed with HHH syndrome at one year of age. At the age of 14, he was referred for the assessment and treatment of his gait disturbance and aggravated weakness of the lower extremities. Brain MRI, electrodiagnostic study and blood test were performed to exclude any lesions related to neurologic dysfunction. Botulinum toxin type A were injected into muscles of adductor longus, adductor magnus, lateral and medial hamstring, and lateral and medial gastrocnemius muscle heads under needle electromyography guidance to reduce lower limb spasticity. Intensive physical therapy including gait training and stretching exercise of adductor and calf muscles were also provided. After intensive physical therapy and botulinum toxin injection to reduce lower limb spasticity, he was able to ambulate for 20 meters independently without any walking aids. There were no adverse events after the injection. Conclusion : Botulinum toxin injection is a safe and effective therapy for patients with HHH syndrome who suffer from gait disturbance.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.50-54
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• 2018

Jehovah's Witnesses do not accept blood transfusions, because of their particular interpretation of the Old and New Testaments. When people with such religious convictions are in need of medical care, their faith and belief may become an obstacle for proper treatment, and pose legal, ethical, and medical challenges for the health care providers. We report two inherited metabolic disorder cases in South Korea where the infants died whilst under medical care because of parental refusal of blood transfusions for religious reasons. Case 1 had methylmalonic acidemia, Down syndrome and associated congenital cardiac anomalies requiring surgery. Case 2 had anemia and methylmalonic acidemia requiring dialysis to treat hyperammonemia and metabolic acidosis. For effective medical management, they needed life-saving blood transfusions. As a part of alternative treatment, Erythropoietin was administered in both cases. As a result, two babies died from their extremely low hemoglobin and hematocrit. The hemoglobin concentrations below 2.7 g/dL without cardiac problem and 5.4 g/dL with cardiac anomaly complicated by pulmonary hypertension are considered life-threatening hemoglobin threshold. The medical professional must respect and accommodate religious beliefs of the patients who can make informed decisions. However, when parents or legal guardians oppose medical treatment of their babies and incompetent care receivers on cultural and religious grounds, the duty to assist and save persons exposed to serious danger, particularly life-threatening events must come first.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.69-76
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• 2017

Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.211-217
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• 2004

Chronic acquired hepatocerebral degeneration(CAHD) is a heterogenous that can occur with a primary neurologic, hepatic, or combined presentation. Symptoms and signs of that included progressive dementia, dysarthria, involuntary movements(including tremor, asterixis, and choreoathetosis), ataxia of limb and gait, typically in a patient with chronic liver cirrhosis. Characteristic radiologic findings is high signal on globus pallidus on T1W1 MRI. Recently, we experienced a patients, a 73-year-old female with CAHD presenting mental change, cognitive deficits, and various involuntary movement. In our patient, T1 weighted MRI of the brain showed symmetric high signal intensity in both basal ganglia. Increased ammonia $level(226{\mu}g/dl)$ in whole blood and a multiple anomalous vessels with spleno-renal shunt on abdominal CT were found. But, liver cirrhosis is absent. In admission care, these mental change and involuntary movements had a good response to herbal medication. We report on patient with CAHD which had a spontaneous spleno-renal shunt without liver disease.

• Journal of Life Science
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• v.26 no.12
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• pp.1477-1486
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• 2016

Lactulose (4-O-${\beta}$-D-galactopyranosyl-D-fructose) is a non-digestible synthetic ketose disaccharide which can used in food and pharmaceutical fields due to its useful functions for encephalopathy, chronic constipation, hyperammonemia, etc. Therefore, the lactulose is regarded as one of the most important disaccharides and have been concentrated much interesting as an attractive functional material in the current industry. From this reason, the research related on the production of lactulose has been carried out various academic and industrial research groups. To produce lactulose, two main methods, chemical production and enzymatic production have been used. Commercially lactulose produced by alkaline isomerization of lactose as chemical production method but it has many disadvantages such as rapid lactulose degradation, purification, and waste management. From these reasons, lactulose produced by enzymatic method which solves these problems has been suggested as a proper method for lactulose production. Two different enzymatic methods have been reported as methods for lactulose production. Lactulose can be obtained through hydrolysis and transfer reaction catalyzed by a ${\beta}$-galactosidase which requires fructose as co-substrate and exhibits a low conversion. Alternatively, lactulose can be produced by direct isomerization of lactose to lactulose catalyzed by cellobiose 2-epimerase which requires lactose as a single substrate and achieves a high lactulose yield. This review summarizes the current state of lactulose production by chemical and biological methods.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.123-134
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• 2014

Recent advances in the diagnosis and treatment of inborn errors of metabolism (IEM) have improved substantially the prognosis of many of these diseases, if diagnosed early enough before irreversible damage occurs. Diseases of inborn errors of metabolism are so diverse over several hundred disease up to now and may be several thousand in near future, and these diversities of IEMs make clinicians embarassed. The signs of neurological dysfunctions of many IEMs manifesting in the neonatal period is very nonspecific, such as poor feeding, poor sucking, apnea or tachypnea, vomiting, hypertonia, hypotonia, seizure, letharginess, consciousness change and coma. But after neonatal period, the signs of neurological deficits become specific and localized. The results of routine basal laboratory tests such as metabolic acidosis, hyperammonemia, lactic acidemia, ketonemia or hyperuricemia can give very important clinical clues for the diagnosis of IEMs. Even no abnormal findings on routine laboratory test could be very important clue for NKH, sulfite oxidase deficiency and peroxisomal disorders. These various clinical manifestations of these diverse diseases can be categorized and summarized. This makes it essential that the practicing clinicians be familiar with the clinical presentations and symptomatic and systematic approaches of these disorders. Characteristic clinical presentations, methods of symptomatic and systematic approach and typing of various disorders is discussed in this review.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.22-27
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• 2021

Propionic acidemia (PA) is an inherited autosomal recessive disorder, due to the deficiency of propionyl-CoA carboxylase (PCC). PCC is the enzyme which catalyzes the conversion of propionyl-CoA to D-methylmalonyl-CoA, and it is critical for the metabolism of amino acids, odd-chain fatty acids, and side chains of cholesterol. The clinical manifestations present mostly at the neonatal period with life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of a 16-year-old Korean boy with late-onset PA who presented with embolic cerebral infarction due to dilated cardiomyopathy (DCMP) with left ventricular noncompaction. And he has family history of sudden cardiac death, so we performed metabolic screening and genetic tests. Elevated levels of 3-hydroxypropionic acid, methylcitric acid and propionylglycerine were detected in urine. Plasma acylcarnitine profile showed elevated propionylcarnitine (C3). Diagnosis of PA was confirmed by genetic analysis, which revealed compound heterozygous mutations, c.[1151T>G] (p.[Phe384Cys]) and c.[1228C>T] (p.[Arg410Trp]) in PCCB gene. His heart function is in improving state and the results of biochemical analysis are stable with heart failure medication and metabolic managements. We present a case of patient without episodes of metabolic decompensation who manifests DCMP as the first symptom of PA.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.68-74
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• 2005

Purpose : There is growing use of continuous renal replacement therapy(CRRT) for pediatric patients, but reports about the use and outcome of CRRT in children is rare in Korea. We report our experiences of CRRT in critically ill pediatric patients. Methods : We reviewed the medical records of 23 pediatric patients who underwent CRRT at Asan Medical Center between May 2001 and May 2004. We evaluated underlying diseases, clinical features, treatment courses, CRRT modalities and outcomes. Results : Ages ranged from three days to 16 years with a median of five years. Patients weighed 2.4 to 63.9 kg(median 23.0 kg; 10 patients ${\leq}20kg$). The underlying diseases were malignancy(nine cases), multiple organ dysfunction syndrome(five cases), hyperammonemia(four cases), acute renal failure associated with liver failure(three cases), dilated cardiomyopathy(one case) and congenital nephrotic syndrome(one case). Pediatric Risk of Mortality(PRISM) III score was $17.6{\pm}7.6$ and the mean number of failing organs was $3.0{\pm}1.7$. Duration of CRRT was one to 27 days(median : nine days). Eleven patients(47.8%) survived. Chronic renal failure developed in two cases, intracranial hemorrhage in one case, and chylothorax in one case among the survivors. PRISM III score and the number of vasopressor before the start of CRRT was significantly lower in the survivors($12.7{\pm}4.2$ and $0.9{\pm}1.1$) compared with nonsurvivors($22.1{\pm}7.8$ and $2.4{\pm}1.4$)(P<0.05). Conclusion : CRRT driven in venovenous mode is an effective and safe method of renal support for critically-ill infants and children to control fluid balance and metabolic derangement. Survival is affected by PRISM III score and the number of vasopressors at the initiation of CRRT.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.199-204
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• 2009

Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.