scholarly journals A rapid ultra performance liquid chromatography tandem mass spectrometric method for measuring amino acids associated with maple syrup urine disease, tyrosinaemia and phenylketonuria

2007 ◽  
Vol 44 (5) ◽  
pp. 474-481 ◽  
Author(s):  
Scott Freeto ◽  
Donald Mason ◽  
Jie Chen ◽  
Robert H Scott ◽  
Srinivas B Narayan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Amino Acid ◽  
Tandem Mass Spectrometry ◽  
Maple Syrup Urine Disease ◽  
Ultra Performance Liquid Chromatography ◽  
Exchange Chromatography ◽  
Tandem Mass ◽  
Maple Syrup ◽  
Urine Disease

Background: Patients with inherited disorders of amino acid metabolism including maple syrup urine disease, tyrosinaemia and phenylketonuria on dietary management require frequent monitoring of disease-relevant plasma amino acids in order to optimize therapeutic benefit. Poorly controlled maple syrup urine disease in particular may result in catastrophic metabolic decompensation. Most methods for monitoring amino acid concentrations are time-consuming and have clinically impractical turnaround times, particularly when the required time to run standards and control samples is taken into account. Methods: We have analysed plasma amino acids using standard ion-exchange chromatography with ninhydrin detection in an amino acid analyser and compared the data with that obtained for the same samples using ultra-performance liquid chromatography (UPLCTM) separation with detection by tandem mass spectrometry. Results: The two methodologies compared very well for the measurement of six important amino acids with correlation coefficients greater than 0.96 for all. The time for sample preparation was longer for the UPLC methodology as batched derivatization and evaporation is required but UPLC-tandem mass spectrometry generated sample results every 8 min while conventional ion-exchange chromatography took almost 1 h per sample. Conclusion: UPLC-tandem mass spectrometry generates data that compares well with existing 'gold standard' methodologies but significantly reduces sample turnaround time. Decreasing the turnaround time for amino acid analyses is very likely to improve clinical care for patients with amino acid disorders as dietary adjustments can be made sooner.

scholarly journals Leucinosis, or maple syrup urine disease (lecture and a clinical case)

2020 ◽  
Vol 48 (4) ◽  
pp. 254-262
Author(s):  
Ju. A. Tsareva ◽  
N. I. Zryachkin ◽  
M. A. Kuznetsova ◽  
E. V. Bogacheva
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Tandem Mass Spectrometry ◽  
Maple Syrup Urine Disease ◽  
Clinical Case ◽  
Branched Chain Amino Acids ◽  
Tandem Mass ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain

Maple syrup urine disease (leucinosis, short-chain ketoaciduria, branched-chain disease, branched-chain ketonuria) is an autosomal recessive disorder which is a consequence of the deficient branched-chain alpha ketoacid dehydrogenase complex. There are five subtypes of the disease: classical, intermediate, intermittent, thiamine-dependent and E3-deficient. Leucinosis is characterized by high plasma levels of branched-chain amino acids (leucine, isoleucine and valine) and high urine levels of branched-chain ketoacids, as well as of lactate and pyruvate. Tandem mass spectrometry can be used as a screening method in newborns. Mild disease cannot be identified at screening. The diagnosis should be based on tandem mass spectrometry of a blood sample and aminoacid analysis by gas chromatography of a urine sample. Prenatal diagnosis requires molecular genetic tests. Treatment of maple syrup urine disease is aimed at normalization of plasma branched-chain amino acids levels and includes two main components, namely, life-long diet therapy and active treatment of acute metabolic deterioration episodes. A favorable course of the disease is possible only with early (pre-symptomatic) initiation of treatment. The development of cognitive functions depends on plasma leucine levels. We present a clinical case of delayed diagnosis of leucinosis, despite its early clinical manifestation, leading to irreversible consequences for the patient.

Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry

1995 ◽  
Vol 41 (1) ◽  
pp. 62-68 ◽  
Author(s):  
D H Chace ◽  
S L Hillman ◽  
D S Millington ◽  
S G Kahler ◽  
C R Roe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Maple Syrup Urine Disease ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Inhibition Assay ◽  
Maple Syrup ◽  
Blood Spots ◽  
Urine Disease ◽  
The Mean

Abstract We report a new method for the diagnosis of maple syrup urine disease (MSUD) from dried blood spots on newborn screening cards based on tandem mass spectrometry (MS-MS). The mean +/- SD concentration of Leu plus Ile in normal newborns was 151 +/- 47 mumol/L (n = 1096); for Val, 131 +/- 58 mumol/L (n = 791). SDs were lower when the concentrations of these amino acids were expressed relative to that of Phe. The mean ratio for Leu + Ile to Phe was 2.5 +/- 0.49; for Val to Phe, 2.18 +/- 0.51. These results compare well with values previously reported in the literature. With these criteria, samples from a collection categorized by a bacterial inhibition assay as normal or falsely positive for MSUD were normal by MS-MS [(Leu + Ile): Phe < 5.0]. Samples from confirmed MSUD patients were categorized as abnormal [(Leu+Ile): Phe > 9.0] by MS-MS.

scholarly journals Determination of free amino acids in plants by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)

2015 ◽  
Vol 7 (18) ◽  
pp. 7574-7581 ◽  
Author(s):  
Magdalena M. Dziągwa-Becker ◽  
Jose M. Marin Ramos ◽  
Jakub K. Topolski ◽  
Wiesław A. Oleszek
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Liquid Chromatography ◽  
Amino Acid ◽  
Tandem Mass Spectrometry ◽  
Free Amino ◽  
Tandem Mass ◽  
Amino Acid Determination ◽  
Acid Determination

Free amino acid determination in plants by LC-MS/MS.

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 Validation of Accuracy-based Amino Acid Reference Materials in Dried-Blood Spots by Tandem Mass Spectrometry for Newborn Screening Assays

1999 ◽  
Vol 45 (8) ◽  
pp. 1269-1277 ◽  
Author(s):  
Donald H Chace ◽  
Barbara W Adam ◽  
S Jay Smith ◽  
J Richard Alexander ◽  
Steven L Hillman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Amino Acid ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Blood Spots ◽  
Amino Acid Contents ◽  
Amino Acid Concentrations

Abstract Background: Advances in technology and the earlier release of newborns from hospitals have pressed the demand for accurate calibration and improved interlaboratory performance for newborn screening tests. As a first step toward standardization of newborn screening aminoacidopathy tests, we have produced six-pool sets of multianalyte dried-blood-spot amino acid reference materials (AARMs) containing predetermined quantities of five amino acids. We describe here the production of the AARMs, validation of their amino acid contents, and characterization of their homogeneity and their stability in storage. Methods: To each of six portions of a pool of washed erythrocytes suspended in serum we added Phe (0–200 mg/L), Leu (0–200 mg/L), Met (0–125 mg/L), Tyr (0–125 mg/L), and Val (0–125 mg/L). Six-pool sets (1300) were prepared, dried, and packaged. We used isotope-dilution mass spectrometry to estimate the endogenous amino acid concentrations of the AARMs and validate their final amino acid concentrations. We used additional tandem mass spectrometry analyses to examine the homogeneity of amino acid distribution in each AARM, and HPLC analyses to evaluate the stability of the amino acid contents of the AARMs. Results: The absolute mean biases across the analytic range for five amino acids were 2.8–9.4%. One-way ANOVAs of the homogeneity results predicted no statistically significant differences in amino acid concentrations within the blood spots or within the pools (P >0.05). Regression slopes (0 ± 0.01) for amino acid concentrations vs storage times and their P values (>0.05) showed no evidence of amino acid degradation at ambient temperatures, 4 °C, or −20 °C during the intervals tested. Conclusion: The validation, homogeneity, and stability of these blood spots support their use as a candidate national reference material for calibration of assays that measure amino acids in dried-blood spots.

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