Defective decarboxylase in branched chain ketoacid oxidase multienzyme complex in classic type of maple syrup urine disease

1972 ◽  
Vol 14 (4) ◽  
pp. 257-263 ◽  
Author(s):  
H. W. R�diger ◽  
U. Langenbeck ◽  
M. Schulze-Schencking ◽  
H. W. Goedde ◽  
L. Schuchmann
Keyword(s):  
Maple Syrup Urine Disease ◽  
Multienzyme Complex ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain

scholarly journals Activities of branched-chain 2-oxo acid dehydrogenase and its components in skin fibroblasts from normal and classical-maple-syrup-urine-disease subjects

1981 ◽  
Vol 200 (1) ◽  
pp. 59-67 ◽  
Author(s):  
D T Chuang ◽  
W L Niu ◽  
R P Cox
Keyword(s):  
Maple Syrup Urine Disease ◽  
Substrate Concentration ◽  
Skin Fibroblasts ◽  
Hill Coefficient ◽  
Multienzyme Complex ◽  
Maple Syrup ◽  
Acid Dehydrogenase ◽  
Sigmoidal Kinetics ◽  
Urine Disease ◽  
Branched Chain

1. Comparisons of the activity and kinetics of the branched-chain 2-oxo acid dehydrogenase in cultured skin fibroblasts from normal and classical maple-syrup-urine-disease (MSUD) subjects provide a kinetic explanation for the enzyme defect. 2. In the intact cell assays, normal fibroblasts demonstrated hyperbolic kinetics with 3-methyl-2-oxo[1-14C]butyrate as a substrate. Intact fibroblasts from four classical MSUD patients showed no decarboxylation over a substrate concentration range of 0.25 to 5.0 mM, and thiamin (4 mM) was without effect. 3. The overall reaction of the multienzyme complex was efficiently reconstituted by using a disrupted-cell system. Normals again showed typical hyperbolic kinetics at the 2-oxo acid concentrations of 0.1 to 5 mM. The Vmax. and apparent Km values were 0.10 +/- 0.02 m-unit/mg of protein and 0.05-0.1 mM respectively, with 3-methyl-2-oxobutyrate. In contrast, classical MSUD patients exhibited sigmoidal kinetics (Hill coefficient, 2.5) with activity approaching 40-60% of the normal value at 5 mM substrate. The K0.5 values from the Hill plots for MSUD patients were 4-7 mM. 4. The E1 (branched-chain 2-oxo acid decarboxylase) component of the multienzyme complex was measured in disrupted-particulate preparations. Normals again showed hyperbolic kinetics with the 2-oxo acid, whereas MSUD preparations exhibited sigmoidal kinetics with the activity of E1 strictly dependent on substrate concentration. Apparent Km or K0.5 were 0.1 and 1.0 mM for normal and MSUD subjects respectively. 5. Measurements of E2 (dihydrolipoyl transacylase) and E3 (dihydrolipoyl dehydrogenase) in MSUD preparations showed them to be in the normal range. 6. The above data suggest a defect in the E1 step of branched-chain 2-oxo acid dehydrogenase in classical MSUD patients.

Neonatal maple syrup urine disease in China: two novel mutations in the BCKDHB gene and literature review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hong‐Hua Jiang ◽  
Yan Guo ◽  
Xian Shen ◽  
Ying Wang ◽  
Ting-Ting Dai ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Chinese Literature ◽  
Brain Mri ◽  
Classical Type ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Gene Testing ◽  
Urine Disease ◽  
Bckdhb Gene ◽  
Branched Chain

Abstract Objectives To report two novel mutations in the BCKDHB gene with Maple syrup urine disease (MSUD) and compare their data with 52 cases of MSUD reported in the available Chinese literature. Methods Clinical data of a case of a newborn with MSUD was retrospectively studied. Literatures on MSUD in the local medical journals from January 1990 till December 2019 in China were reviewed. Results Two novel BCKDHB mutations c.90_91insCTGGCGCGGGG (p.Phe35TrpfsTer41) and c.80_90del (p.Ala32PhefsTer48) were identified. We found a total of 52 cases of MSUD reports so far. A total of 49 cases had the symptom of poor feeding (94.2%), 50 cases showed poor responses to stimulation (96.2%), 21 cases had odor of maple syrup (40.3%), 29 cases had seizures (55.7%), and 13 cases had respiratory failure (25.0%). The average of the blood ammonia was 127.2 ± 75.0 μmol/L. A total of 18 cases reported the gene testing, among of them 9 cases of BCKDHA mutations, 6 cases of BCKDHB mutations, and 2 cases of DBT mutations. A total of 13 cases (25%) were treated with mechanical ventilation, 50 cases (96.2%) with protein-restricted diet and l-carnitine, 29 cases with thiamine, and only 2 cases were treated with blood purification. Finally, 19 patients (36.5%) were died, 21 cases (40.4%) were improved after treatments. Conclusions The clinical phenotype of neonatal MSUD in China belongs to the classical type currently. Suspected patients should have blood or urine branched-chain amino acid levels tested and brain MRI as early as possible to enable early diagnosis, thus improvement in prognosis.

scholarly journals Maple syrup urine disease: magnetic resonance imaging findings in three patients

2021 ◽  
pp. 1-11
Author(s):  
Aliya Allahwala ◽  
Sibtain Ahmed ◽  
Bushra Afroze
Keyword(s):  
Magnetic Resonance Imaging ◽  
Amino Acids ◽  
Magnetic Resonance ◽  
Maple Syrup Urine Disease ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Resonance Imaging ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain

Abstract Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder, caused by branched-chain alpha-ketoacid dehydrogenase (BCKD) deficiency, leading to toxic accumulation of branched-chain amino acids (BCAAs) including leucine, isoleucine and valine and their corresponding ?-ketoacids. The diagnosis of MSUD is based on elevated BCAAs and allo-isoleucine in plasma, and branched-chain hydroxyacids and ketoacids in urine. The identification of alloisoleucine >5 µmol/L is considered pathognomonic. Moreover, brain magnetic resonance imaging (MRI) showing atypical signal intensity and oedema is characteristic of MSUD. Recognition of the classical neuro-radiological findings of MSUD is particularly useful in local settings as many healthcare facilities lack the resources to measure Plasma Amino Acids (PAA). We report three cases of MSUD, in whom the disorder was strongly suspected at presentation, based on classical brain MRI findings, which was urgently confirmed by PAA analysis Continuous...

Rapid diagnosis of maple syrup urine disease (branched chain ketoaciduria) by micro-enzyme assay in leukocytes and fibroblasts

1973 ◽  
Vol 45 (4) ◽  
pp. 433-440 ◽  
Author(s):  
U. Wendel ◽  
W. Wöhler ◽  
H.W. Goedde ◽  
U. Langenbeck ◽  
E. Passarge ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Enzyme Assay ◽  
Rapid Diagnosis ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain

THE DIAGNOSIS OF MAPLE SYRUP URINE DISEASE (Branched-chain Ketoaciduria)

PEDIATRICS ◽  
1963 ◽  
Vol 32 (2) ◽  
pp. 234-238
Author(s):  
Joseph Dancis ◽  
Joel Hutzler ◽  
Mortimer Levitz
Keyword(s):  
Amino Acids ◽  
Maple Syrup Urine Disease ◽  
Oxidative Decarboxylation ◽  
Maple Syrup ◽  
Peripheral Leukocyte ◽  
Metabolic Block ◽  
Urine Disease ◽  
Branched Chain ◽  
Normal Leukocyte

The metabolism of the three branched-chain amino acids has been investigated in vitro, using the peripheral leukocyte. The normal leukocyte can transaminate and decarboxylate the three amino acids. These functions are demonstrable at birth. Five cases of maple syrup urine disease (branched-chain ketoaciduria) were studied. The peripheral leukocyte could transaminate the three amino acids, but decarboxylation was greatly reduced or absent. This confirms the site of metabolic block in maple syrup urine disease, and suggests an early and specific approach to diagnosis. Oxidative-decarboxylation of the branched-chain ketoacids involves an enzyme common to all three ketoacids.

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