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.

MAPLE SYRUP URINE DISEASE: BRANCHED-CHAIN KETO-ACIDURIA

PEDIATRICS ◽  
1960 ◽  
Vol 25 (1) ◽  
pp. 72-79
Author(s):  
Joseph Dancis ◽  
Mortimer Levitz ◽  
Roland G. Westall
Keyword(s):  
Amino Acids ◽  
Maple Syrup Urine Disease ◽  
Animal Experiments ◽  
Oxidative Decarboxylation ◽  
Maple Syrup ◽  
Keto Acids ◽  
Metabolic Degradation ◽  
Urine Disease ◽  
Branched Chain ◽  
Derivatives Of

A case of maple syrup urine disease is presented. The patient lived for 20 months, the longest survival so far reported. There were increased amounts of leucine, isoleucine and valine in plasma and urine, indicating a block in the metabolic degradation of these amino acids. There was an accumulation in the urine of the respective keto acids, but not of the aldehydes or of the simple acids. This locates the block at a step common to all three amino acids, that of oxidative-decarboxylation. The alpha-hydroxy-acid derivatives of these amino acids are probably present, but the evidence is still incomplete. Animal experiments indicate that oxidative decarboxylation of the branched-chain amino acids is a metabolic step which is found generally in tissues, including leukocytes but probably not erythrocytes.

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...

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.

scholarly journals Skin Lesions Associated with Dietary Management of Maple Syrup Urine Disease: a Case Report

2015 ◽  
Vol 7 (4) ◽  
pp. 153-162 ◽  
Author(s):  
Jana Kazandjieva ◽  
Dimitrina Guleva ◽  
Assia Nikolova ◽  
Sonya Márina
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Maple Syrup Urine Disease ◽  
Skin Lesions ◽  
Branched Chain Amino Acids ◽  
Acrodermatitis Enteropathica ◽  
Metabolic Decompensation ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain

Abstract Leucinosis (maple syrup urine disease - MSUD) is an inherited aminoacidopathy and organic aciduria caused by severe enzyme defect in the metabolic pathway of amino acids: leucine, isoleucine, and valine. The classical variant of the disease is characterized by accumulation of both amino and α-keto acids, particulary the most toxic rapid elevation of circulating leucine and its ketoacid, α-ketoisocaproate, which cause encephalopathy and life-threatening brain swelling. However, patients with the most severe form, classical maple syrup urine disease, may appear normal at birth, but develop acute metabolic decompensation within the first weeks of life with typical symptoms: poor feeding, vomiting, poor weight gain, somnolence and burnt sugar-smelling urine, reminiscent of maple syrup. Early diagnosis and dietary intervention improve the patient’s condition, prevent severe complications, and may allow normal intellectual development. We present a 4-month old infant with leucinosis dignosed 3 months earlier, due to elevated levels of amino acids: leucine, isoleucine and valine. The patient was full-term neonate with an uncomplecated delivery, without any family history of metabolic disorder or consanguinity. The infant was referred to a dermatologist, because of maculopapular exanthema on the scalp, trunk, upper and lower extremities, and exfoliative dermatitis of the perioral, particularly anogenital regions, associated with diarrhea. Skin involvement was associated with poor general condition of the infant exhibiting severe hypotension, anemic syndrome, dyspepsia and neurological symptoms. Exanthema developed a few days after the initiation of nutritional therapy for MSUD: isoleucine-, leucine-, and valine-free powdered medical food (MSUD-2) supplemented with iron. Zink levels were within normal ranges. Rapid skin improvement occurred after adequate branched-chain amino acids supplementation was commenced under regular laboratory control (normal zinc serum level with deficiencies of leucine and valine), skin hygiene with antiseptics, emollients and low potent topical corticosteroids. Treatment of acute metabolic decompensation and dietary restriction of branched-chain amino acids are the main aspects in the management of maple syrup urine disease. Common findings in patients with MSUD include: plasma amino acid imbalance, particularly of essential amino acids, failure to thrive attributed to restriction of particular precursor amino acids and natural proteins, micronutrient deficiencies or higher energy requirement due to chronic illness or inflammation. Due to low intake of branched-chain amino acids, some patients develop skin lesions known as acrodermatitis enteropathica-like syndrome. Here we report a case of an infant who developed acrodermatitis enteropathica-like skin eruptions due to branched-chain amino acid deficiency during treatment of maple syrup urine disease. According to available world literature, this is the first report of acrodermatitis enteropathica-like syndrome in an infant with maple syrup urine disease (leucinosis) in the Republic of Bulgaria.

scholarly journals Branched Chain Amino Acids Induce Apoptosis in Neural Cells without Mitochondrial Membrane Depolarization or Cytochromec Release: Implications for Neurological Impairment Associated with Maple Syrup Urine Disease

2000 ◽  
Vol 11 (5) ◽  
pp. 1919-1932 ◽  
Author(s):  
Philippe Jouvet ◽  
Pierre Rustin ◽  
Deanna L. Taylor ◽  
Jennifer M. Pocock ◽  
Ursula Felderhoff-Mueser ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cytochrome C ◽  
Maple Syrup Urine Disease ◽  
Mitochondrial Membrane ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Maple Syrup ◽  
Mitochondrial Membrane Depolarization ◽  
Urine Disease ◽  
Branched Chain

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain α-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular α-keto isocaproic acid, specifically induced apoptosis in glial and neuronal cells in culture. Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, α-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their α-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway.

scholarly journals Hereditary characteristics of the S339L mutation in a patient with maple syrup urine disease in Vietnam

2020 ◽  
Vol 42 (2) ◽  
Author(s):  
Nguyen Thi Thu Huong ◽  
Vu Chi Dung ◽  
Nguyen Thi Thanh Ngan ◽  
Nguyen Kim Thoa ◽  
Nguyen Huy Hoang
Keyword(s):  
Amino Acids ◽  
Maple Syrup Urine Disease ◽  
Neurological Complications ◽  
Scientific Basis ◽  
Homozygous Mutation ◽  
Maple Syrup ◽  
Urine Disease ◽  
Bckdhb Gene ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by malfunction of the branched-chain α-ketoacid dehydrogenase complex (BCKDH). This enzyme complex participates in the catalyzing metabolisms of the branched-chain α-ketoacids, the second step of the degradation of branched-chain amino acids. Impaired activities of the BCKAD complex lead to an increase of the levels of branched- chain amino acid such as leucine, valine, and isoleucine in the blood. In children with maple syrup urine disease, catalysis of the metabolisms of some amino acids failed to be implemented, leading to an accumulation of the amino acids which has been shown as one of the causes of neurological complications, intellectual disabilities, and nervous paralysis or even death. Pathogenic mutations normally occur in BCKDHA, BCKDHB, DBT and DLD genes which encode the E1α, E1β, and E2 subunits of the BCKDH complex. In the present study, a homozygous mutation in the BCKDHB gene (c. 1016C>T) in a pediatric patient with MSUD diagnosed at The National Hospital of Pediatrics was identified using whole exome and Sanger sequencing methods. As a result, the inheritance of the homozygous mutation related to MSUD in BCKDHB gene within the pedigree of the patient’s family was determined. The results indicated that the mutation in the BCKDHB gene was inherited from both of the patient’s parents. In addition, this finding provides an important scientific basis to  researches on MSUD in the Vietnamese population. 

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