Recentes avanços em erros inatos do metabolismo

Diament, Aron J.

doi:10.1590/S0004-282X1987000200011

Resumos

Apresenta-se análise dos avanços concernentes aos erros inatos do metabolismo (EIM) sob 4 aspectos: 1) da compreensão geral dos EIM, principalmente relacionados aos mecanismos, à localização gênica e à manifestação dos genes pela heterogenidade genética; 2) aos aspectos clínicos, apresentando de forma resumida a descrição ou de novas variantes dos EIM já conhecidos ou de novos EIM; 3) ao diagnóstico, em que se apresentam os meios diagnósticos de laboratório atualmente disponíveis em nosso meio: seja a dosagem de marcadores genéticos, sejam os testes de triagem populacionais a nível de berçário, sejam detecções de heterozigotos, assim como o diagnóstico pré-natal; 4) aos aspectos terapêuticos, em que são apresentadas as variadas terapêuticas substitutivas, ou dietas especiais, ou ainda as técnicas de plasmaferese e leucoferese, apresentando, quanto a esta última, alguns resultados observados em 4 mucopolissacaridoses.

Four aspeets of advances in inborn errors of metabolism (IEM) are analysed: 1) concerning the general comprehension of the pathogenesis, genic localization and genetic heterogeneity; 2) clinicai aspeets, with description of new variants of known IEM or new IEM; 3) laboratory diagnostic tests presently used in our country: dosage of some genetic markers (arylsulfatases, hexosaminidases, beta-glicosidase; beta-galactosidase and sphingomyelinase), newborn populational screening (for hyperphenylalaninemia, and hypothyroidism), heterozygote detection (for Tay-Sachs disease) and also some prenatal diagnosis; 4) therapeutic aspects presenting substitutive treatment, special diets, plasma pheresis and leucopheresis. The first results of 4 cases of mucopolysacharidosis treated with the last technic are presented.

Recentes avanços em erros inatos do metabolismo

Inborn errors of metabolism: recent advances

Aron J. Diament

Professor Adjunto do Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Chefe do Serviço de Neurologia Infantil do Hospital das Clínicas da FMUSP

RESUMO

Apresenta-se análise dos avanços concernentes aos erros inatos do metabolismo (EIM) sob 4 aspectos: 1) da compreensão geral dos EIM, principalmente relacionados aos mecanismos, à localização gênica e à manifestação dos genes pela heterogenidade genética; 2) aos aspectos clínicos, apresentando de forma resumida a descrição ou de novas variantes dos EIM já conhecidos ou de novos EIM; 3) ao diagnóstico, em que se apresentam os meios diagnósticos de laboratório atualmente disponíveis em nosso meio: seja a dosagem de marcadores genéticos, sejam os testes de triagem populacionais a nível de berçário, sejam detecções de heterozigotos, assim como o diagnóstico pré-natal; 4) aos aspectos terapêuticos, em que são apresentadas as variadas terapêuticas substitutivas, ou dietas especiais, ou ainda as técnicas de plasmaferese e leucoferese, apresentando, quanto a esta última, alguns resultados observados em 4 mucopolissacaridoses.

SUMMARY

Four aspeets of advances in inborn errors of metabolism (IEM) are analysed: 1) concerning the general comprehension of the pathogenesis, genic localization and genetic heterogeneity; 2) clinicai aspeets, with description of new variants of known IEM or new IEM; 3) laboratory diagnostic tests presently used in our country: dosage of some genetic markers (arylsulfatases, hexosaminidases, beta-glicosidase; beta-galactosidase and sphingomyelinase), newborn populational screening (for hyperphenylalaninemia, and hypothyroidism), heterozygote detection (for Tay-Sachs disease) and also some prenatal diagnosis; 4) therapeutic aspects presenting substitutive treatment, special diets, plasma pheresis and leucopheresis. The first results of 4 cases of mucopolysacharidosis treated with the last technic are presented.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Clínica Neurológica, FMUSP - Caixa Postal 3461 - 01000 - São Paulo, SP - Brasil.

1. ARGOV, Z. & NAVON, R. - Clinical and genetic variations in the syndrome of adult GM gangliosidosis resulting from hexosaminidase A deficiency. Ann. Neurol. 16:14, 1984.
2. BLASS, J. P. - Inborn errors of pyruvate metabolism. In ref. 27 ,pg. 193.
3. BOUÉ, J.; DELUCHAT, C.; NICOLAS, H.; OURY, J.F. & DUMEZ, Y. - Diagnostic prenatal des maladies géniques sur villosites choriales. J. Génet. Human. 34:221, 1986.
4. BROWN, G.K.; HUNT, S.M.; SCHOLEM, R.; FOWLER, K.; GRIMES, A.; MERCER, J.F.B.; TRUSCOTT, R.M.; COTTON, R.G.H.; ROGERS, J.G. & DANKS, D.M. - Beta-hydroxyisobutyril coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations. Pediatrics 70:532, 1982.
5. DE VIVO, D.C.; HAYMOND, M.W.; OBERT, K.A.; NELSON, J.S. & PAGLIARA, A.S. - Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). Ann. Neurol. 6:483, 1979.
6. DIAMENT, A. J.; SCHMIDT, B.J. & ROSEMBERG, S. - O diagnostic© neurope-diatrico em deficiencia mental. Anais Nestle no 104, 1980.
7. DIAMENT, A.J. - O diagnostico pre-natal em Neurologia Infantil. In A.J. Diament (ed.): Neurologia Infantil. Ed. 2. 1986 (no prelo).
8. DURAN, M.; BEEMER, F.A.; TIBOSCH, A.S.; BRUINVIS, L.; KETTING, D. & WADMAN. S.K. - Inherited 3-methylglutaconic aciduria in two brothers-another defect of leucine metabolism. J. Pediatr. 101:551, 1982.
9. EGGER, J.: PINCOTT, J.R.; WILSON, J. & ERDOHAZI, M. - Cortical subacute necrotizing encephalomyelopathy: a study of two patients with mitochondrial dysfunction. Neuropediatrics 15:150, 1984.
10. ENDO, F.; KITANO, A.; UEHARA, I.; NAGATA, N.; MATSUDA, I.; SHINKA, T.; KUHARA, T. & MATSUMOTO, I. - Four-hydroxyphenylpyruvic acid oxidase deficiency with normal fumarylacetoacetase: a new variant form of hereditary hypcrtyrosinemia. Pediatr. Res. 17:92, 1983.
11. van ERVEN, P.M.M.; RUITENBEEK, W.; GABRELLS, F.J.M. & RENIER, WO. - Disturbed oxidative metabolism in subacute necrotizing encephalomyelopathy (Leigh syndrome). Neuropediatrics 17:28, 1986.
12. FOX, J.; HACK, A.M.; GOLBUS, M.S.; WINTER, S.; KALOUSEK, F.; ROZEN, R.; BRUSILOW, S.W. & ROSENBERG, L.E. - Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms. New Engl. J. Med. 315:1205, 1986.
13. GOLJAARD, H. - Genetic Metabolic Diseases. Early Diagnosis and Prenatal Analysis. Elsevier/North-Holland, Amsterdam, 1980, pg. 3, 507.
14. GIBSON, K.M.; SWEETMAN, L.; NYHAN, W.L.; JAKOBS, C.; RATING, D.; SIEMES, H. & HANEFELD, F. - Succinic semialdehyde dehydrogenase deficiency: an inborn error of gumma-aminobutyric acid metabolism. Clin. chim. Acta. 133:33, 1983.
15. JAEKEN, J.; CASAER, P.; COCK, P. de; CORBEEL, L.; EECKELS, R.; EGGERMONT, E.; SCHECHTER, P.J. & BRUCCHER, J.M. - Gamma-aminobutyric acid transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics 15:165, 1984.
16. McKUSICK, V.A. - Mendelian Inheritance in Man. Catalogue of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotype. Ed. 6. Johns Hopkins Univ. Press, Baltimore, 1983, pg. xi.
17. MEISTER, A. - 5-oxoprolinuria (pyroglutamic aciduria) and other disorders of gamma-glutamil cycle. In ref. 27, pg. 348.
18. MUDD, S.H. & LEVY, H.L. - Disorders of transsulfuration. In ref. 27.
19. PEIFFER, J.; HARZER, K.; SCHLOTE, W. - Diffuse-disseminated sclerosis combined with partial arylsulfate A(ASA) deficiency: mixed heterozygosity of ASA-and pseudo-ASA-deficiency. Neuropediatrics 15:59, 1984.
20. ROSENBERG, L.E. - Disorders of propínate and methylmalonate metabolism. In ref. 27, pg. 474.
21. SCHINZEL, A. - Catalogue of Unbalanced Chromosome Aberrations in Man. Walter de Gruyter, Berlin, 1984, pg 1.
22. SCHMIDT, B.J. & DIAMENT, A.J. - Erros inatos do metabolismo: diagnóstico e «screening» populacional. Pediat. Prát. (São Paulo), edição comemorativa (1929-1979, pg. 20.
23. SCHMIDT, B. J.; SOLBERG, P.C.; DIAMENT, A.J. & PIMENTEL, H. - Phenylketonuria in a patient with congenital hypothyroidism. Pediatr. Res. 2:176, 1981.
24. SCHMIDT, B.J.; DIAMENT, A.J.; KRYNSKI, S.; KAMEI, M.E.; RODRIGUES, M.M.C. & TAKATA, S. - Neonatal mass screening of hereditary metabolic diseases in S. Paulo-Brazil. Acta paediatr. jpn. 24:75, 1982.
25. SCHMIDT, B.J. - Tratamento dos erros inatos do metabolismo. In A.J. Diamcnt (ed.): Neurologia Infantil. Ed. 2. 1986 (no prelo).
26. SWAIN, J.L.; SABINA, R.L. & HOLMES, E.W. - Myoadenilate deaminase deficiency. In ref. 27, pg. 1184.
27. STANBURY, J.B.; WYNGAARDEN, J.B.; FREDERICKSON, D.S.; GOLDSTEIN, J.L. & BROWN, M.S. (eds.): The Metabolic Basis of Inherited Disease. Ed. 5. McGraw-Hill, New York, 1983.
28. STANBURY, J.B.; WYNGAARDEN, J.B.; FREDERICKSON, D.S.; GOLDSTEIN, J.L. & BROWN, J.L. - Inborn errors of metabolism in the 1980s. In ref. 27, pg. 3.
29. TANAKA, K. & ROSENBERG, L.E. - Disorders of branched chain amino acid and organic acid metabolism. In ref. 27, pg. 440.
30. TOURIAN, A. & SIDBURY, J.B. - Phenylketonuria and hyperphenylalaninemta. In ref. 27, pg. 270.
31. VALLE, D. & SIMELL, O. - The hyperornithinemias. In ref. 27, pg. 382.
32. WENGER, D.A.; SUJANSKY, E.; FENNESSEY, P.V. & THOMPSON, J.N. - Human beta-mannosidase deficiency. New Engl. J. Med. 315:1201, 1986.
33. WHO Working Group-Fetal diagnosis of hereditary diseases. Bull. World Health Organiz. 62:345, 1984.
34. WOLF, B.; HEARD, G.S.; JEFFERSON, L.G.; PROUD, V.K.; NANCE, W.E. & WEISSBECKER, B.A. - Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program. New Engl. J. Med. 313: 16, 1985.
35. YOSHIDA, T.: TADA, K. & ARAKAWA, T. - Vitamin B₆ dependency of glutamic acid decarboxylase in the kidney from a patient with vitamin B, - dependent convulsion. Tokotu J. exp. Med. 104:195, 1971.
36. ZINN, A.B.; KERR, D.S. & HOPPEL, C.L. - Fumarase deficiency: a new case of mitochondrial encephalomyopathy. New Engl. J. Med. 315:169, 1986.

Datas de Publicação

Publicação nesta coleção
22 Jun 2011
Data do Fascículo
Jun 1987

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

[1] 1. ARGOV, Z. & NAVON, R. - Clinical and genetic variations in the syndrome of adult GM gangliosidosis resulting from hexosaminidase A deficiency. Ann. Neurol. 16:14, 1984.

[2] 2. BLASS, J. P. - Inborn errors of pyruvate metabolism. In ref. 27 ,pg. 193.

[3] 3. BOUÉ, J.; DELUCHAT, C.; NICOLAS, H.; OURY, J.F. & DUMEZ, Y. - Diagnostic prenatal des maladies géniques sur villosites choriales. J. Génet. Human. 34:221, 1986.

[4] 4. BROWN, G.K.; HUNT, S.M.; SCHOLEM, R.; FOWLER, K.; GRIMES, A.; MERCER, J.F.B.; TRUSCOTT, R.M.; COTTON, R.G.H.; ROGERS, J.G. & DANKS, D.M. - Beta-hydroxyisobutyril coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations. Pediatrics 70:532, 1982.

[5] 5. DE VIVO, D.C.; HAYMOND, M.W.; OBERT, K.A.; NELSON, J.S. & PAGLIARA, A.S. - Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). Ann. Neurol. 6:483, 1979.

[6] 6. DIAMENT, A. J.; SCHMIDT, B.J. & ROSEMBERG, S. - O diagnostic© neurope-diatrico em deficiencia mental. Anais Nestle no 104, 1980.

[7] 7. DIAMENT, A.J. - O diagnostico pre-natal em Neurologia Infantil. In A.J. Diament (ed.): Neurologia Infantil. Ed. 2. 1986 (no prelo).

[8] 8. DURAN, M.; BEEMER, F.A.; TIBOSCH, A.S.; BRUINVIS, L.; KETTING, D. & WADMAN. S.K. - Inherited 3-methylglutaconic aciduria in two brothers-another defect of leucine metabolism. J. Pediatr. 101:551, 1982.

[9] 9. EGGER, J.: PINCOTT, J.R.; WILSON, J. & ERDOHAZI, M. - Cortical subacute necrotizing encephalomyelopathy: a study of two patients with mitochondrial dysfunction. Neuropediatrics 15:150, 1984.

[10] 10. ENDO, F.; KITANO, A.; UEHARA, I.; NAGATA, N.; MATSUDA, I.; SHINKA, T.; KUHARA, T. & MATSUMOTO, I. - Four-hydroxyphenylpyruvic acid oxidase deficiency with normal fumarylacetoacetase: a new variant form of hereditary hypcrtyrosinemia. Pediatr. Res. 17:92, 1983.

[11] 11. van ERVEN, P.M.M.; RUITENBEEK, W.; GABRELLS, F.J.M. & RENIER, WO. - Disturbed oxidative metabolism in subacute necrotizing encephalomyelopathy (Leigh syndrome). Neuropediatrics 17:28, 1986.

[12] 12. FOX, J.; HACK, A.M.; GOLBUS, M.S.; WINTER, S.; KALOUSEK, F.; ROZEN, R.; BRUSILOW, S.W. & ROSENBERG, L.E. - Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms. New Engl. J. Med. 315:1205, 1986.

[13] 13. GOLJAARD, H. - Genetic Metabolic Diseases. Early Diagnosis and Prenatal Analysis. Elsevier/North-Holland, Amsterdam, 1980, pg. 3, 507.

[14] 14. GIBSON, K.M.; SWEETMAN, L.; NYHAN, W.L.; JAKOBS, C.; RATING, D.; SIEMES, H. & HANEFELD, F. - Succinic semialdehyde dehydrogenase deficiency: an inborn error of gumma-aminobutyric acid metabolism. Clin. chim. Acta. 133:33, 1983.

[15] 15. JAEKEN, J.; CASAER, P.; COCK, P. de; CORBEEL, L.; EECKELS, R.; EGGERMONT, E.; SCHECHTER, P.J. & BRUCCHER, J.M. - Gamma-aminobutyric acid transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics 15:165, 1984.

[16] 16. McKUSICK, V.A. - Mendelian Inheritance in Man. Catalogue of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotype. Ed. 6. Johns Hopkins Univ. Press, Baltimore, 1983, pg. xi.

[17] 17. MEISTER, A. - 5-oxoprolinuria (pyroglutamic aciduria) and other disorders of gamma-glutamil cycle. In ref. 27, pg. 348.

[18] 18. MUDD, S.H. & LEVY, H.L. - Disorders of transsulfuration. In ref. 27.

[19] 19. PEIFFER, J.; HARZER, K.; SCHLOTE, W. - Diffuse-disseminated sclerosis combined with partial arylsulfate A(ASA) deficiency: mixed heterozygosity of ASA-and pseudo-ASA-deficiency. Neuropediatrics 15:59, 1984.

[20] 20. ROSENBERG, L.E. - Disorders of propínate and methylmalonate metabolism. In ref. 27, pg. 474.

[21] 21. SCHINZEL, A. - Catalogue of Unbalanced Chromosome Aberrations in Man. Walter de Gruyter, Berlin, 1984, pg 1.

[22] 22. SCHMIDT, B.J. & DIAMENT, A.J. - Erros inatos do metabolismo: diagnóstico e «screening» populacional. Pediat. Prát. (São Paulo), edição comemorativa (1929-1979, pg. 20.

[23] 23. SCHMIDT, B. J.; SOLBERG, P.C.; DIAMENT, A.J. & PIMENTEL, H. - Phenylketonuria in a patient with congenital hypothyroidism. Pediatr. Res. 2:176, 1981.

[24] 24. SCHMIDT, B.J.; DIAMENT, A.J.; KRYNSKI, S.; KAMEI, M.E.; RODRIGUES, M.M.C. & TAKATA, S. - Neonatal mass screening of hereditary metabolic diseases in S. Paulo-Brazil. Acta paediatr. jpn. 24:75, 1982.

[25] 25. SCHMIDT, B.J. - Tratamento dos erros inatos do metabolismo. In A.J. Diamcnt (ed.): Neurologia Infantil. Ed. 2. 1986 (no prelo).

[26] 26. SWAIN, J.L.; SABINA, R.L. & HOLMES, E.W. - Myoadenilate deaminase deficiency. In ref. 27, pg. 1184.

[27] 27. STANBURY, J.B.; WYNGAARDEN, J.B.; FREDERICKSON, D.S.; GOLDSTEIN, J.L. & BROWN, M.S. (eds.): The Metabolic Basis of Inherited Disease. Ed. 5. McGraw-Hill, New York, 1983.

[28] 28. STANBURY, J.B.; WYNGAARDEN, J.B.; FREDERICKSON, D.S.; GOLDSTEIN, J.L. & BROWN, J.L. - Inborn errors of metabolism in the 1980s. In ref. 27, pg. 3.

[29] 29. TANAKA, K. & ROSENBERG, L.E. - Disorders of branched chain amino acid and organic acid metabolism. In ref. 27, pg. 440.

[30] 30. TOURIAN, A. & SIDBURY, J.B. - Phenylketonuria and hyperphenylalaninemta. In ref. 27, pg. 270.

[31] 31. VALLE, D. & SIMELL, O. - The hyperornithinemias. In ref. 27, pg. 382.

[32] 32. WENGER, D.A.; SUJANSKY, E.; FENNESSEY, P.V. & THOMPSON, J.N. - Human beta-mannosidase deficiency. New Engl. J. Med. 315:1201, 1986.

[33] 33. WHO Working Group-Fetal diagnosis of hereditary diseases. Bull. World Health Organiz. 62:345, 1984.

[34] 34. WOLF, B.; HEARD, G.S.; JEFFERSON, L.G.; PROUD, V.K.; NANCE, W.E. & WEISSBECKER, B.A. - Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program. New Engl. J. Med. 313: 16, 1985.

[35] 35. YOSHIDA, T.: TADA, K. & ARAKAWA, T. - Vitamin B₆ dependency of glutamic acid decarboxylase in the kidney from a patient with vitamin B, - dependent convulsion. Tokotu J. exp. Med. 104:195, 1971.

[36] 36. ZINN, A.B.; KERR, D.S. & HOPPEL, C.L. - Fumarase deficiency: a new case of mitochondrial encephalomyopathy. New Engl. J. Med. 315:169, 1986.