Leucodistrofia metacromática: estudo dos aminácidos livres no sangue, urina, saliva e líquido cefalorraqueano

Escalante, Ovidio D.; Amaral, Ary Domingos do; Canelas, Horacio M.

doi:10.1590/S0004-282X1964000300003

Resumos

É registrado, presumivelmente pela primeira vez na literatura, o aumento da aminacidúria em casos de leucodistrofia metacromática. Mediante cromatografia circular e bidimensional foram estudados os aminácidos livres na urina, sangue, saliva e líquido cefalorraqueano de dois casos familiais de leucodistrofia metacromática. No sangue foi verificado aumento da concentração de cistina, ácido as-pártico, glicina, ácido glutâmico, alanina, prolina, tirosina e fenilalanina. Na urina encontravam-se elevados o ácido aspártico, cistina, alanina, prolina, tirosina e fenilalanina. Na saliva foi notado aumento do ácido a-y-diaminobutírico, ácido glutâmico, alanina e prolina. No líquido cefalorraqueano o ácido aspártico, alanina, prolina e fenilalanina encontravam-se em maiores concentrações. Além disso, estavam presentes 6 aminácidos não identificados. Um dêles desintegrava-se em três componentes e uma destas frações comportava-se como um polipeptídeo, provàvelmente identificável a uma substância composta de ácido glutâmico, glicina e ácido aspártico. Esta substância poderia integrar um complexo polipéptido-lipídico resultante de um dismetabolismo lipídico, já conhecido nas leucodistrofias, associado a um distúrbio do metabolismo protêico, agora relatado. Os resultados são comparados com os dados referidos na literatura relativa às concentrações de aminácidos no líquido cefalorraqueano e urina de algumas afecções nervosas de caráter desmielinizante. No líquido cefalorraqueano o perfil da leucodistrofia metacromática se assemelha aos anteriormente encontrados na moléstia de Niemann-Pick, na degeneração ce-rebromacular e na "esclerose difusa". Na urina as alterações se aproximam das que ocorrem na moléstia de Hartnup.

Increased aminoaciduria in metachromatic leucodystrophy is demonstrated, presumably for the first time. By means of circular and two-dimensional chromatography, the free amino acids of urine, blood, saliva, and cerebrospinal fluid of two familial cases of juvenile metachromatic leucodystrophy were studied. In blood an increased concentration of cystine, aspartic acid, glycine, glutamic acid, alanin, proline, tyrosine, and phenylalanin was found. In urine, cystine, aspartic acid, alanin, proline, tyrosine, and phenylalanin showed increased levels. In saliva a-y-diaminobutyric acid, glutamic acid, alanin, and proline were mostly concentrated. In cerebrospinal fluid aspartic acid, alanin, proline, and phenylalanin were found in greater concentrations. Besides, 6 non-identified amino acids were present. One of them disintegrated into 3 components and one of these fractions behaved like a polypeptide, seemingly identifiable to a compound substance of glutamic acid, glycine, and aspartic acid. This substance could integrate a polypeptid-lipid complex resulting from a lipid dysmetabolism, already known in the leucodystrophies, allied to a proteid dysmetabolism, now reported. The results are compared with the data reported in the literature regarding the concentrations of amino acids in the cerebrospinal fluid and urine of some nervous diseases showing demyelinating processes. In CSF the pattern of metachromatic leucodystrophy resembles those previously found in Niemann-Pick disease, cerebromacular degeneration, and "diffuse sclerosis". In urine the pattern resembles that of Hartnup disease.

Metachromatic leucodystrophy: study of the free amino acids in blood, urine, saliva and cerebrospinal fluid

Leucodistrofia metacromática: estudo dos aminácidos livres no sangue, urina, saliva e líquido cefalorraqueano

Ovidio D. Escalante^I; Ary Domingos do Amaral^II; Horacio M. Canelas^I

^I(Chairman: Prof. Adherbal Tolosa) and the Center of Nuclear Medicine; From the Department of Neurology

^II(Director: Dr. Tede Eston; Head, Division of Biological Research: Dr. Veronica Rapp de Eston), University of São Paulo School of Medicine, Brazil

ABSTRACT

Increased aminoaciduria in metachromatic leucodystrophy is demonstrated, presumably for the first time. By means of circular and two-dimensional chromatography, the free amino acids of urine, blood, saliva, and cerebrospinal fluid of two familial cases of juvenile metachromatic leucodystrophy were studied.

In blood an increased concentration of cystine, aspartic acid, glycine, glutamic acid, alanin, proline, tyrosine, and phenylalanin was found. In urine, cystine, aspartic acid, alanin, proline, tyrosine, and phenylalanin showed increased levels. In saliva a-y-diaminobutyric acid, glutamic acid, alanin, and proline were mostly concentrated. In cerebrospinal fluid aspartic acid, alanin, proline, and phenylalanin were found in greater concentrations.

Besides, 6 non-identified amino acids were present. One of them disintegrated into 3 components and one of these fractions behaved like a polypeptide, seemingly identifiable to a compound substance of glutamic acid, glycine, and aspartic acid. This substance could integrate a polypeptid-lipid complex resulting from a lipid dysmetabolism, already known in the leucodystrophies, allied to a proteid dysmetabolism, now reported.

The results are compared with the data reported in the literature regarding the concentrations of amino acids in the cerebrospinal fluid and urine of some nervous diseases showing demyelinating processes. In CSF the pattern of metachromatic leucodystrophy resembles those previously found in Niemann-Pick disease, cerebromacular degeneration, and "diffuse sclerosis". In urine the pattern resembles that of Hartnup disease.

RESUMO

É registrado, presumivelmente pela primeira vez na literatura, o aumento da aminacidúria em casos de leucodistrofia metacromática. Mediante cromatografia circular e bidimensional foram estudados os aminácidos livres na urina, sangue, saliva e líquido cefalorraqueano de dois casos familiais de leucodistrofia metacromática.

No sangue foi verificado aumento da concentração de cistina, ácido as-pártico, glicina, ácido glutâmico, alanina, prolina, tirosina e fenilalanina. Na urina encontravam-se elevados o ácido aspártico, cistina, alanina, prolina, tirosina e fenilalanina. Na saliva foi notado aumento do ácido a-y-diaminobutírico, ácido glutâmico, alanina e prolina. No líquido cefalorraqueano o ácido aspártico, alanina, prolina e fenilalanina encontravam-se em maiores concentrações.

Além disso, estavam presentes 6 aminácidos não identificados. Um dêles desintegrava-se em três componentes e uma destas frações comportava-se como um polipeptídeo, provàvelmente identificável a uma substância composta de ácido glutâmico, glicina e ácido aspártico. Esta substância poderia integrar um complexo polipéptido-lipídico resultante de um dismetabolismo lipídico, já conhecido nas leucodistrofias, associado a um distúrbio do metabolismo protêico, agora relatado.

Os resultados são comparados com os dados referidos na literatura relativa às concentrações de aminácidos no líquido cefalorraqueano e urina de algumas afecções nervosas de caráter desmielinizante. No líquido cefalorraqueano o perfil da leucodistrofia metacromática se assemelha aos anteriormente encontrados na moléstia de Niemann-Pick, na degeneração ce-rebromacular e na "esclerose difusa". Na urina as alterações se aproximam das que ocorrem na moléstia de Hartnup.

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ACKNOWLEDGMENTS

We are indebted to Dr. Yolanda Tavares, head of the Section on Biochemistry of the Instituto Adolfo Lutz (São Paulo, SP, Brazil) for the assistance in the technical elaboration of this manuscript.

This study was supported by a grant of the Brazilian Ministry of Health; From the Department of Neurology

Clinica Neurológica - Caixa Postal 3461 - São Paulo - Brasil

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4. BARGETON, E. - The metachromatic form of leucodystrophy and its relationship to lipidosis and demyelination in other metabolic disorders. In Folch-Pi, J. & Bauer, H. J.: Brain Lipids and Lipoproteins, and the Leucodystrophies. Amsterdam, Elsevier, 1963, p. 101.
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6. BEARN, A. G.; KUNKEL, H. G. - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J. clin. Invest. 33:400-409, 1954.
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18. EVERED, D. F. - The excretion of amino acids by the human; a quantitative study with ion-exchanging chromatography. Biochem. J. 62:416-427, 1956.
19. FOSDICK, L. S.; BLACKWELL, R. Q. - The determination of amino acid content of fresh and putrified saliva by paper partition chromatography. J. dent. Res. 28:644, 1949.
20. FOWLER, D. I.; NORTON, P. M.; CHEUNG, M. W.; PRATT, E. L. - Observations on the urinary amino acids excretion in man; the influence of age and diet. Arch. Biochem. 68:452-466, 1957.
21. GOLDBERG, H. J. V.; GILDA, J. E.; TISHKOPF, G. H. - Paper partition chromatography: free amino acids in saliva. J. dent. Res. 27:493-496, 1948.
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27. KEMALI, P. - Sulle eredo-degenerazioni spino-cerebellari e sulle relative forme di associazione. Acta neurol. (Napoli) 9:358-380, 1954.
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32. LOGOTHETIS, J. - Cerebrospinal fluid free amino acids in neurologic diseases: observations in aspartic acid concentrations. Neurology (Minneap.) 8:374-376, 1958.
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Datas de Publicação

Publicação nesta coleção
16 Ago 2013
Data do Fascículo
Set 1964

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. AUSTIN, J. H. - Metachromatic form of diffuse cerebral sclerosis. I: Diagnosis during life by urine sediment examination. Neurology (Minneap.) 7:415-426, 1957.

[2] 2. ARMSTRONG, M. D.; SHAW, K. N. F. - Studies on phenylketonuria. III: The metabolism of o-tyrosine. J. biol. Chem. 213:805-811, 1955.

[3] 3. AWAPARA, J. - Application of paper chromatography to the estimation of free amino acids in tissues. Arch. Biochem. 19:172-173, 1948.

[4] 4. BARGETON, E. - The metachromatic form of leucodystrophy and its relationship to lipidosis and demyelination in other metabolic disorders. In Folch-Pi, J. & Bauer, H. J.: Brain Lipids and Lipoproteins, and the Leucodystrophies. Amsterdam, Elsevier, 1963, p. 101.

[5] 5. BARON, D. N.; DENT, C. E.; HARRIS, H.; HART, E. W.; JEPSON, J. B. - Hereditary pellagralike skin rash with temporary cerebellar ataxia, constant renal aminoaciduria, and other bizarre biochemical features. Lancet II:421-428, 1956.

[6] 6. BEARN, A. G.; KUNKEL, H. G. - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J. clin. Invest. 33:400-409, 1954.

[7] 7. BERRY, H. K. - Further studies in individual urinary and salivary amino acid patterns. Univ. Texas Publ., No. 5109, p. 157-164.

[8] 8. BERRY, H. K.; CAIN, L. - Quantitative studies of urinary and salivary amino acids using paper chromatography. Univ. Texas Publ., No. 5109, p. 71-76.

[9] 9. BLOCK, R. J.; DURRUM, E. L.; ZWEIG, G. - A Manual of Paper Chromatography and Paper Electrophoresis. New York, Academic, 1955.

[10] 10. CAMPOS, J. V. M.; ROTHSTEIN, W.; PONTES, J. F. - A dosagem do nitrogênio amínico no sôro sangüíneo e na urina pelo método de Troll e Cannan. Rev. Hosp. Clín. Fac. Med. São Paulo 13:284-290, 1958.

[11] 11. CANELAS, H. M.; ESCALANTE, O. D.; IRIYA, K.; De JORGE, F. B. - Leucodistrofia metacromática: estudo clínico-laboratorial de cinco casos na mesma familia. Rev. paul. Med. 63:355-376, 1963.

[12] 12. CANELAS, H. M.; ESCALANTE, O. D.; IRIYA, K.; De JORGE, F. B. - The diagnosis of metachromatic leucodystrophy during life: metachromatic lipids in saliva and cerebrospinal sediments and in the parotid glands. Arq. Neuro-psiquiat. (S. Paulo) 22:122-128, 1964.

[13] 13. COPPER, A. M.; ECKARDT, R. D.; FALOON, W. E.; DAVIDSON, C. S. - Investigation of the aminoaciduria in Wilson's disease (hepatolenticular degeneration): demonstration of a defect in renal function. J. clin. Invest. 29:265-278, 1950.

[14] 14. CURTIUS, F. - Familiäre diffuse Sklerose und familiäre spastische Spinalparalyse in einer Sippe: ein Beitrag zur Genealogie der Heredodegenerationen. Z. ges. Neurol. Psychiat. 126:209-227, 1930.

[15] 15. DANCIS, J. M.; LEVITZ, M.; MILLER, S.; WESTALL, R. G. - Maple syrup urine disease. Brit, med. J. i:91-93, 1959.

[16] 16. DIEZEL, P. B. - Lipidosis of the central nervous system. In Cumings, J. N.: Modern Scientific Aspects of Neurology. London, Arnold, 1960, p. 135.

[17] 17. EFRON, M. L. - Two-way separation of amino acids and other nin-hydrin-reacting substances by high-voltage electrophoresis followed by paper chromatography. Biochem. J. 72:691-694, 1959.

[18] 18. EVERED, D. F. - The excretion of amino acids by the human; a quantitative study with ion-exchanging chromatography. Biochem. J. 62:416-427, 1956.

[19] 19. FOSDICK, L. S.; BLACKWELL, R. Q. - The determination of amino acid content of fresh and putrified saliva by paper partition chromatography. J. dent. Res. 28:644, 1949.

[20] 20. FOWLER, D. I.; NORTON, P. M.; CHEUNG, M. W.; PRATT, E. L. - Observations on the urinary amino acids excretion in man; the influence of age and diet. Arch. Biochem. 68:452-466, 1957.

[21] 21. GOLDBERG, H. J. V.; GILDA, J. E.; TISHKOPF, G. H. - Paper partition chromatography: free amino acids in saliva. J. dent. Res. 27:493-496, 1948.

[22] 22. HARPER, H. A.; DOOLAN, P. D. - The renal aminoacidurias. Clin. Chem. 9:19-26, 1963.

[23] 23. HIER, S. W.; BERGEIM, O. - The microbiological determination of certain amino acids in human and dog plasma. J. biol. Chem. 163:129-135, 1946.

[24] 24. HUISMAN, T. H. J. - Onderzoek naar het gehalte aan verschillende aminoazuren van de liquor cerebrospinalis. Ned, T. Geneesk. 99:3357-3361, 1955.

[25] 25. JOHNSON, C. A.; BERGEIM, O. - The distribution of free amino acids between erythrocytes and plasma in man. J. biol. Chem. 188:833-838, 1951.

[26] 26. KASTAN, M. - Different forms of diffuse sclerotic process - Pelizeus-Merzbacher disease, Struempell's familial spastic paralysis, leucodystrophy - in one family. J. nerv. ment. Dis. 101:357-362, 1945.

[27] 27. KEMALI, P. - Sulle eredo-degenerazioni spino-cerebellari e sulle relative forme di associazione. Acta neurol. (Napoli) 9:358-380, 1954.

[28] 28. KIRCH, E. R.; KESEL, R. G.; O'DONNELL, J. F.; WACH, E. C. - Amino acids in human saliva. J. dent. Res. 26:297-301, 1947.

[29] 29. LEDERER, M. - Chromatographic Reviews: Progress in Chromatography, Electrophoresis and Related Methods. Amsterdam, Elsevier, 1959.

[30] 30. LOGOTHETIS, J. - A study of free amino acids in the human cerebrospinal fluid. Neurology (Minneap.) 5:767-776, 1955.

[31] 31. LOGOTHETIS, J. - Free amino acid content of cerebrospinal fluid in humans and dogs. Neurology (Minneap.) 8:299-302, 1958.

[32] 32. LOGOTHETIS, J. - Cerebrospinal fluid free amino acids in neurologic diseases: observations in aspartic acid concentrations. Neurology (Minneap.) 8:374-376, 1958.

[33] 33. LOGOTHETIS, J.; BOVIS, M. - Quantitative two-dimensional chromatography for free amino acids in cerebrospinal fluid analysis. Wld Neurol. 2:747-761, 1961.

[34] 34. LOGOTHETIS, J.; BOVIS, M. - Free amino acids changes in the spinal fluid of patients with central nervous system degenerative and chronic epileptic disorders. Wld Neurol. 3:466-474, 1962.

[35] 35. LUDEWIG, S. - Glutamine, glutamic acid, and 7-aminobutyric acid in cerebro- spinal fluids. Arch. Neurol. Psychiat. (Chic.) 70:268-270, 1953.

[36] 36. MABRY, C. C; TODD, W. R. - Quantitative measurement of individual and total free amino acids in urine. J. Lab. clin. Med. 61:146-157, 1983.

[37] 37. MACKENZIE, D. Y.; WOOLF, L. I. - Maple syrup urine disease; an inborn error of the metabolism of valine, leucine, and isoleucine associated with gross mental deficiency. Brit. med. J. i:90-91, 1959.

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