scholarly journals Clinical utility of low branched-chain amino acid modular diets in patients with isovaleric aciduria and maple syrup urine disease

2021 ◽  
Vol 27 (2) ◽  
Author(s):  
Suthida Chatvuttinun ◽  
◽  
Duangrurdee Wattanasirichaigoon ◽  
Visith Chavasit ◽  
Oraporn Dumrongwongsiri ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Clinical Investigation ◽  
Tube Feeding ◽  
The Other ◽  
Organic Acidurias ◽  
Food Ingredients ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain ◽  
Isovaleric Aciduria

Introduction: Modular diets (MDs) with low amount of offending amino acids have been developed using locally available food ingredients as alternatives to commercial formulas for the treatment of branched-chain organic acidurias (BCOAs). Herein, we conducted a clinical investigation of MDs in patients with BCOAs. Methods: Modular diet A (MDA), with low leucine was produced for maple syrup urine disease (MSUD), and modular diet B (MDB) products, MDB-1, -2, -3, and -4, with low leucine, valine, methionine and threonine were made for isovaleric aciduria (IVA)/methylmalonic aciduria (MMA)/propionic aciduria (PA). Children aged 4-18 years, with MSUD, IVA, PA or MMA were invited to participate in the study. The research subjects switched from metabolic formula protocol to modular diet protocol. They were followed-up at 0, 1, 2, 4, and 6 months. Clinical efficacies of MDs were determined by completion of study, compliance to MDs, clinical outcomes and complications, and parental satisfaction. Results: Six children (2 MSUD and 4 IVA) participated and completed the study. Compliance to MDA was 100% in MSUD subjects with G-tube feeding, while compliance to MDB varied among self-fed individuals with IVA. One subject with MSUD was clinically stable throughout the study, while the other experienced metabolic instability. All IVA individuals showed clinical and laboratory stability during the study. One MSUD and three IVA families preferred the metabolic formula, whereas the other IVA family reported no preference and the other MSUD subject preferred MDs. Conclusion: We provided a proof of concept in developing modular diets for BCOAs, and showed favourable outcomes when using MDs in IVA and varying clinical benefits in MSUD.

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

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.

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.

scholarly journals Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

2020 ◽  
Vol 21 (20) ◽  
pp. 7490
Author(s):  
Jing Xu ◽  
Youseff Jakher ◽  
Rebecca C. Ahrens-Nicklas
Keyword(s):  
Amino Acids ◽  
Maple Syrup Urine Disease ◽  
Attention Deficit Disorder ◽  
Neurological Disorders ◽  
Survival Rates ◽  
Branched Chain Amino Acids ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain ◽  
The Brain

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.

Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease

2018 ◽  
Vol 31 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Monica Zeynalzadeh ◽  
Alireza Tafazoli ◽  
Azadeh Aarabi ◽  
Morteza Moghaddassian ◽  
Farah Ashrafzadeh ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Energy Levels ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Strong Correlations ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Abstract Background: Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by dysfunction of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. The current study analyzed seven Iranian MSUD patients genetically and explored probable correlations between their genotype and phenotype. Methods: The panel of genes, including BCKDHA, BCKDHB and DBT, was evaluated, using routine the polymerase chain reaction (PCR)-sequencing method. In addition, protein modeling (homology and threading modeling) of the deduced novel mutations was performed. The resulting structures were then analyzed, using state-of-the-art bioinformatics tools to better understand the structural and functional effects caused by mutations. Results: Seven mutations were detected in seven patients, including four novel pathogenic mutations in BCKDHA (c.1198delA, c.629C>T), BCKDHB (c.652C>T) and DBT (c.1150A>G) genes. Molecular modeling of the novel mutations revealed clear changes in the molecular energy levels and stereochemical traits of the modeled proteins, which may be indicative of strong correlations with the functional modifications of the genes. Structural deficiencies were compatible with the observed phenotypes. Conclusions: Any type of MSUD can show heterogeneous clinical manifestations in different ethnic groups. Comprehensive molecular investigations would be necessary for differential diagnosis.

scholarly journals Electrochemical (Bio)Sensing of Maple Syrup Urine Disease Biomarkers Pointing to Early Diagnosis: A Review

2020 ◽  
Vol 10 (20) ◽  
pp. 7023
Author(s):  
Sophia Karastogianni ◽  
Stella Girousi
Keyword(s):  
Maple Syrup Urine Disease ◽  
Point Mutations ◽  
Branched Chain Amino Acids ◽  
Genetic Defects ◽  
Maple Syrup ◽  
Disease Biomarkers ◽  
Neurocognitive Dysfunctions ◽  
Urine Disease ◽  
Branched Chain ◽  
Genomic Disorders

Metabolic errors are inherited diseases, where genetic defects prevent a metabolic path, ending up in enzyme malfunction. In correspondence to its remaining or plenitude fall of enzymatic potency, there is an amassment of dangerous metabolites near the metabolic bar and/or a dearth of necessary products, inducing a certain disease. These metabolic errors may include deviations such as point mutations, expunctions or interferences, or further complicated genomic disorders. Based on these facts, maple syrup urine disease (MSUD) is a scarce metabolic disease, generated by huge concentrations of branched-chain amino acids (b AAs), i.e., leucine, isoleucine, and valine. In this situation, these large amounts of b AAs provoke abnormalities such as liver failure, neurocognitive dysfunctions, and probably death. To overpass those problems, it is crucial to implement a timely and agile diagnosis at the early stages of life in view of their immutable consequence on neonates. Thus, this review will describe MSUD and b AAs analysis based on electrochemical (bio)sensing.

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