Determination of α-keto acids as silylated oximes in urine and serum by combined gas chromatography-mass spectrometry

A 7 1/2-year-old girl with hypermethioninemia, myopathy, and mental deficiency (IQ = 65) is described. The increased methionine was not associated with deficiency of methionine adenosyltransferase, which was normal or increased in liver, muscle, erythrocytes, and cultured fibroblasts. Methionyl-tRNA synthetase in fibroblasts was normal. The hypermethioninemia and a concurrently increased blood S-adenosylmethionine declined on a diet low in methionine. There was a diffuse, symmetrical, moderate proximal muscle weakness, but muscle atrophy was not discernible, and the deep tendon reflexes were hypoactive but obtainable. Electromyographic abnormalities were not detected. Electron microscopy of muscle revealed 3 to 6 small myelin figures in the region of the I band in nearly every fiber, with occasional myelin figures at other sites also. These myelin figures were more numerous and smaller than those seen accompanying nonspecific myopathies and may reflect a more specific pathological change. Electron microscopy of liver revealed three nonspecific lesions in all hepatocytes: (1) numerous megamitochondria with crystalloid deposit in the matrix; (2) increased numbers of small vesicles of smooth endoplasmic reticulum; and (3) loss of plasma membrane microvilli, with extensive bleb formation and shedding of cytoplasm into Disse's space.

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“…A complete blood count was normal. No abnormal volatile or nonvolatile organic acids were seen by gas chromatography [40].…”

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confidence: 85%

Methioninemia and myopathy: A new disorder

Gaull

Bender

Vulovic

et al. 1981

Annals of Neurology

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“…A gas chromatography-mass spectrometry (GC-MS) system comprising a 5890A Series II chromatograph and a 5971A mass spectrometer (Hewlett-Packard, Analytical Product Group, Delaware, USA) was used for the analysis of urinary organic acids. Trimethylsilyl derivatives of organic acids were prepared as described by Sternowsky et al, 30 and identification of the derivatives were made according to the methods described by Chalmers and Lawson, 31 Lefevere et al 32 and Toshimitsu Niwa. 33 Quantitation and identification of glycosaminoglycans (GAG) in urine were made by a direct dye-binding assay procedure, 34,35 and high-resolution electrophoresis respectively.…”

Section: Methodsmentioning

confidence: 99%

Study of Inherited Metabolic Disorders in Singapore – 13 Years Experience

Tan

Gajra

Lim

2006

Ann Acad Med Singap

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Introduction: Recommended by the National Advisory Council of the Disabled, the Ministry of Health of Singapore supported a nationwide study of inherited metabolic disorders (IMDs). When the 5-year project ended, investigations were provided as a diagnostic service. This paper documents our 13-year experience. Materials and Methods: Patients with symptoms suggestive of an IMD were referred. Investigations on heparinised blood and/or urine included amino acid analysis using a Beckman 6300 Amino Acid Analyser, organic acids analysis using a Hewlett-Packard gas chromatography and mass spectrometry, mucopolysaccharides quantitative assay and high-resolution electrophoresis, sugars by thin-layer chromatography. Results: Of the 3656 patients studied from 1992 to 2005, IMDs were found in 127 (77 males; 50 females; age range, 1 day to 56 years). Their ethnic distribution was: 55.1% Chinese, 19.7% Malays, 11.0% Indians, 11.0% other races and 3.2% unknown. IMD diagnosed comprised 41 (32.3%) organic acidurias, 34 (26.8%) amino acidaemias/acidurias, 14 (11.0%) urea cycle defects, 15 (11.8%) mucopolysaccharidoses, 6 (4.7%) carbohydrate disorders and 17 (13.4%) others. Twenty-three (18.1%) cases were diagnosed during the neonatal period and 36 (28.3%) after the age of 13. Conclusion: Positive detection rate was 3.5% and 48 IMDs were found. Significant proportion of cases had late-onset IMDs. Early identification of IMDs permits timely management, genetic counselling and prenatal diagnosis.

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“…Separation and identification of the organic acid derivatives were achieved using the Hewlett Packard 5890A Series II chromatograph and 5971A mass spectrometer (GC-MS System by Hewlett-Packard, Analytical Product Group, Delaware, USA). [3][4][5][6] Urine mucopolysaccharides were measured using the dimethylmethylene blue (DMB) dyebinding method. 7,8 Separation of the various mucopolysaccharides was achieved by high-resolution electrophoresis (HRE) on cellulose acetate plates.…”

Section: Methodsmentioning

confidence: 99%

External Proficiency Testing Programmes in Laboratory Diagnoses of Inherited Metabolic Disorders

Tan

Gajra

Lim

2006

Ann Acad Med Singap

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Introduction: This paper shows the importance and value of external proficiency testing programmes in monitoring and improving a laboratory’s diagnostic skills. It reviews and documents the wide variety of inherited metabolic disorders (IMDs) encountered in the programmes organised by the Human Genetics Society of Australasia and the College of American Pathologists. Materials and Methods: The programmes used actual patient specimens to assess a laboratory’s ability to provide diagnoses based on laboratory tests results and brief clinical information. Participating laboratory was also required to suggest additional test(s) to confirm diagnoses. Results: The results of diagnoses on 116 samples were reviewed. Altogether 49 IMDs were encountered, including 26 organic acidurias, 16 aminoacidurias, 3 urea cycle defects, 5 mucopolysaccharidoses, and 1 each of mucolipidosis and purine disorder. Our report for 21 of the 116 samples (18.1%) deviated from the actual diagnoses. Deviations from the final diagnoses were recorded along with the reasons for them. The main reasons for the deviations were: the lack of standards for recognising metabolites of pathognomonic significance, absence of characteristic metabolites in samples collected during treatment, the presence of misleading unusual metabolites, inadequate clinical information, and inability to perform additional tests due to insufficient specimens. Conclusions: The programmes provided a wide variety of IMDs, some of which we have yet to encounter in our patients. They also enabled us to learn about the varied biochemical manifestations at different stages of disease and the identity of previously unidentified metabolites. They enhanced our knowledge and experience and improved our diagnostic skills. Key words: External proficiency testing, Inherited metabolic disorders, Laboratory diagnosis, Quality assessment

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Determination of α-keto acids as silylated oximes in urine and serum by combined gas chromatography-mass spectrometry

Cited by 49 publications

References 13 publications

Methioninemia and myopathy: A new disorder

Methioninemia and myopathy: A new disorder

Study of Inherited Metabolic Disorders in Singapore – 13 Years Experience

External Proficiency Testing Programmes in Laboratory Diagnoses of Inherited Metabolic Disorders

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