Maple syrup urine disease(MSUD) is an autosomal recessive disorder involving the metabolism of the branched-chain amino acids(BCAA) such as leucine, isoleucine and valine. The disorder is due to a defect in branched-chain alpha-ketoacid dehydrogenase(BCKAD) and the classic form causes rapid progressive and overwhelming illness beginning in the first weeks of life, present with poor feeding, lethargy, change in muscle tone, acidosis, seizures and coma. The goal of therapy in acutely ill patients with MSUD is an immediate reduction in the plasma levels of the BCAAs and branched-chain ketoacids. In this report, we describe an infant with MSUD who was treated by dietary therapy alone. During the therapy, acrodermatitis enteropathica-like syndrome developed with low plasma isoleucine concentration while she was receiving a formula deficient in BCAAs.
Acer* ; Acidosis ; Acrodermatitis* ; Amino Acids, Branched-Chain ; Coma ; Diet Therapy* ; Diet* ; Humans ; Infant ; Isoleucine ; Lethargy ; Leucine ; Maple Syrup Urine Disease* ; Metabolism ; Plasma ; Seizures ; Valine

PURPOSE: The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy. MATERIALS AND METHODS: Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored. RESULTS: Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043). CONCLUSION: Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.
Amino Acids, Branched-Chain ; Body Mass Index ; Carcinoma, Hepatocellular ; Cholesterol ; Hepatitis Viruses ; Humans ; Isoleucine ; Korea ; Leucine ; Liver ; Oxytetracycline ; Plasma ; Serum Albumin ; Valine

PURPOSE: The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy. MATERIALS AND METHODS: Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored. RESULTS: Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043). CONCLUSION: Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.
Amino Acids, Branched-Chain ; Body Mass Index ; Carcinoma, Hepatocellular ; Cholesterol ; Hepatitis Viruses ; Humans ; Isoleucine ; Korea ; Leucine ; Liver ; Oxytetracycline ; Plasma ; Serum Albumin ; Valine

Maple syrup urine disease (MSUD) is an autosomal recessive disease caused by a deficiency in subunits of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDH). The disease is characterized by the accumulation of the branched-chain amino acids leucine, isoleucine, valine, alloisoleucine, and their corresponding alpha-ketoacid in blood and urine. MSUD is a heterogenous disorder, and classic, intermittent, intermediate and thiamine-responsive phenotypes have been identified. We experienced a case of Maple syrup urine disease (classic type) in a female neonate, who suffered from lethargy, poor feeding, apnea, alternating periods of hypertonicity and flaccidity, generalized convulsions, and a peculiar burned sugar smell from the body and urine. She died of respiratory failure 22 days after the birth. The brief review of the literature was made.
Acer* ; Amino Acids, Branched-Chain ; Apnea ; Burns ; Female ; Humans ; Infant, Newborn ; Isoleucine ; Lethargy ; Leucine ; Maple Syrup Urine Disease* ; Oxidoreductases ; Parturition ; Phenotype ; Respiratory Insufficiency ; Seizures ; Smell ; Valine

BACKGROUND/AIMS: A prospective comparative study was conducted to investigate the efficacy of orally administered branched-chain amino acids (BCAA) in cirrhotic patients. METHODS: Forty-seven patients with liver cirrhosis of viral etiologies, whose hypoalbuminemia could not be corrected with adequate protein intake, were randomly assigned to either the BCAA group (n=31) or the control group (n=16). The selection criteria were ages between 16 and 70 years, patients whose Child-Pugh scores were less than 13 points and who were willing to participate in the study. Most patients (87.1%) belonged to Child-Pugh class B. Patients in the BCAA group received oral supplementation with branched-chain amino acid granules (12 g/day, each packet containing total 4 g of BCAA, i.e. leucine, 1904 mg; valine, 1144 mg; isoleucine, 952 mg) for 12 weeks. Patients had complete blood counts and chemistry at entry and once every month. Serum ferritin and amino acid concentrations in plasma were determined. Anthropometric parameters including body weight, body fat contents and body mass index were assessed at the beginning and at the end of the 3-month period. RESULTS: In the BCAA group, there was a significant increment in plasma levels of isoleucine, valine (p < 0.001) whereas levels of aromatic amino acids did not show substantial change. Total BCAA concentration and BCAA/AAA (aromatic amino acid) molar ratio (Fischer's ratio) also increased significantly after the administration of oral BCAA (p < 0.001). In contrast, patients in the control group showed no significant change in assessed parameters. CONCLUSION: Oral supplementation of BCAA to cirrhotic patients improved several parameters reflecting nutritional status without causing encephalopathy or other serious adverse effects.
Adipose Tissue ; Amino Acids, Aromatic ; Amino Acids, Branched-Chain ; Blood Cell Count ; Body Mass Index ; Body Weight ; Chemistry ; Ferritins ; Humans ; Hypoalbuminemia ; Isoleucine ; Leucine ; Liver Cirrhosis ; Molar ; Nutritional Status* ; Patient Selection ; Plasma ; Prospective Studies* ; Valine

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
Valine ; Corynebacterium glutamicum/genetics* ; Metabolic Engineering ; Amino Acids, Branched-Chain ; Bioreactors

There have been reports that hyperammonemia and amino acid disturbance can cause loss of consciousness in patients with multiple myelomas and normal liver function. We experienced a case of a 71-years-old female patient with amyloidosis, who had shown disturbance of consciousness. At that time, the serum ammonia level was elevated; serum amino acids disturbance was also noted. In particular, the decrease in branched-chain amino acids and increase in aromatic amino acids results in a low Fisher ratio. The Fisher ratio, the ratio of branched-chain to aromatic amino acids, has been suggested as an important indicator of consciousness disturbance. We report, for the first time in Korea, a case of amyloidosis, with mental disturbance due to serum amino acid disturbance.
Amino Acids ; Amino Acids, Aromatic ; Amino Acids, Branched-Chain ; Ammonia ; Amyloidosis* ; Consciousness ; Female ; Humans ; Hyperammonemia* ; Korea ; Liver ; Multiple Myeloma ; Unconsciousness

OBJECTIVE: The EXforge Clinical evaluation of amlodlpine and valsarTan in hypErtension (EXCITE) study was designed to evaluate the real-world effectiveness and safety of amlodipine/valsartan (Aml/Val) and amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCT) single-pill combination (SPC) in patients with hypertension.
METHODOLOGY: This 26-week observational, multicenter, prospective, open-label study included patients aged ? 18 years of age with established diagnosis of hypertension. The change in mean sitting systolic BP (msSBP), diastolic BP (msDBP) from baseline to Week 26, proportion of patients achieving BP goal (msSBP/msDBP <130/80 mmHg and <140/90 mmHg for patients with and without diabetes,respectively) at endpoint, and safety were monitored. Here, we report the data of patients from the Philippines.
RESULTS: Of the total 1,054 patients in the full analysis set (Aml/Val, n=928; Aml/Val/HCTZ, n=126), 923 (87.6%) patients completed the study. The baseline BP was 158.5/96.5 and 167.0/99.5 mmHg in the Aml/Val and Aml/Val/HCTZ groups,respectively. Significant reductions in msSBP and msDBP from baseline to week 26 were observed with both Aml/Val (-31.9/-19.2 mmHg). Adverse events were reported by 8.8% of the patients.
CONCLUSION: The Aml/Val and Aml/Val/HCTZ SPCs were effective in controlling BP and were generally well tolerated in patients with hypertension from the Philippines.

Human ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; Amlodipine ; Amlodipine, Valsartan Drug Combination ; Diabetes Mellitus ; Hydrochlorothiazide ; Hypertension ; Philippines ; Tetrazoles ; Valine ; Valsartan

A 1-year-old female with maple syrup urine disease presenting with erythematous, partially eroded plaques on the trunk, anogenital area, and extremities experienced metabolic crisis. The skin lesions appeared at 11 months of age and was thought to result from amino acid imbalance secondary to erratic supplementation of specialized milk formula devoid of isoleucine, leucine, and valine. Serial urine monitoring showed persistent ketones and elevated serum leucine and valine. The patient was managed with emollients, intralipid 20%, and addition of isoleucine and valine supplements to counter the neurotoxic effect of leucine. After 8 days of proper feeding and continuous emollient application, the lesions improved and skin biopsy revealed superficial perivascular dermatitis. Although a decrease in erythema and desquamation was noted, the patient had persistent cerebral edema and continued to deteriorate.

Maple Syrup Urine Disease ; Isoleucine ; Leucine ; Valine ; Erythema

OBJECTIVETo analyze and summarize clinical manifestation of maple syrup urine disease (MSUD) of neonates.

METHODSData of two cases with neonatal MSUD and the reports of 15 cases seen in the past 15 years in China were reviewed and analyzed.

RESULTSThere was an increasing number of reports of cases with neonatal MSUD. All the 17 cases had the symptom of poor feeding between 3 h and 8 d after birth; 7 cases had family history; 14 cases showed progressive neurologic signs. Odor of maple syrup occurred in 8 cases. Blood levels of branched-chain amino acids (BCAA) significantly increased in 13 cases and 6 neonates were diagnosed using tandem mass spectrometry. Urinary levels of BCAA and metabolite elevated in 12 cases and 5 neonates were diagnosed using gas chromatography-mass spectrometry. MRI/CT demonstrated abnormal signal in 10 cases. Twelve cases died or their parents gave up treatment and one case had cerebral palsy; 4 cases were treated with BCAA-free formula milk and showed improved outcome.

CONCLUSIONNewborns with MSUD often had early appeared non-specific symptoms with poor feeding and lethargy, most cases later showed an odor resembling maple syrup and neurologic signs. For patients who were suspected of having MSUD, blood and urine concentrations of BCAA should be tested for early diagnosis. Specific MRI edema signal from brain suggests the possibility of MSUD. Early intervention and treatment after diagnosis, with compliance of parents, would improve the patient's outcome.

Amino Acids, Branched-Chain ; blood ; urine ; Humans ; Infant, Newborn ; Male ; Maple Syrup Urine Disease ; diagnosis