Abstract
A girl with non-ketotic hyperglycinaemia was treated for 2 years with a synthetic diet consisting of a glycine- and serine-free amino-acid mixture, glucose, fat, minerals, and vitamins.
The addition of sodium benzoate to this diet resulted in only a temporary decrease of the plasma glycine concentration.
Addition of 300 mg methionine/kg/day led to a marked reduction of glycine in the plasma but also to an excessive increase of the methionine plasma concentration. L-methionine at a lower dose did not influence the plasma glycine level.
During the dietary treatment an almost normal gain of body weight was observed, though the psychomotor development was not influenced.
Post mortem the following changes were noted:
-
1.
reduced myelination of the white matter;
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2.
spongiform alterations of the white matter of the cerebrum, the cerebellum, and the spinal cord;
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3.
inclusions of birefringent crystals in liver and brain.
The grey matter of the cerebrum did not show any marked alterations. In peripheral nerves no areas of demyelination or inclusions of crystals were found.
Zusammenfassung
Es wird über eine Patientin mit einer nichtketotischen Hyperglycinämie berichtet, die 2 Jahre lang mit einer vollsynthetischen Kost aus einem Aminosäurengemisch, Mineralien, Glucose, Fett und Vitaminzusätzen behandelt wurde.
Die diätetische Behandlung sowie Zusatz von Natrium-Benzoat zur Nahrung führten nur kurzfristig zu einem Absinken der Plasma-Glycin-Konzentrationen.
Nach Anreicherung der Nahrung mit L-Methionin in einer Dosierung von 300 mg/kg KG/die zeigten sich zwar deutlich niedrigere Glycinspiegel, gleichzeitig kam es aber zu einer exzessiven Hypermethioninämie. L-Methionin-Gabe in Dosierungen von 150–200 mg/kg KG hatten keinen Einfluß auf die Höhe des Plasma-Glycin-Spiegels.
Die körperliche Entwicklung des Kindes unter Diätbehandlung war altersentsprechend. Ein Einfluß auf die geistige Entwicklung wurde nicht bemerkt, es bestand aber bereits zu Beginn der Behandlung das Bild einer Decrebrierung. Pathologisch-histologisch zeigten sich Veränderungen des ZNS in Form von Markscheidenreifungshemmung und einer spongiösen Degeneration der weißen Substanz in Großhirn, Kleinhirn und Rückenmark sowie Einlagerungen von doppeltbrechenden Kristallen. In der grauen Substanz waren keine groben Alterationen nachweisbar. Im Bereich des peripheren Nervensystems fanden sich keine Markscheidenausfälle und keine doppeltbrechenden Kristalle.
Die Leber zeigte eine leichte Vacuolisierung der Leberzellen und eine starke Einlagerung von doppeltbrechenden Kristallen in Parenchymzellen und Makrophagen.
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Literatur
Anderson, J. M.: Spongy degeneration in the white matter of the central nervous system in the newborn: Pathological findings in three infants, one with hypeglycinemia. J. Neurol. Neurosurg. Psychiat. 32, 328 (1969)
Ando, T., Arakawa, T., Tada, K.: Glycine serine interconversion in the heterocygotes of hyperglycinemia. The 4th Proceedings of Pediatric Research on Metabolism, Kyoto 1966
Ando, T., Nyhan, W. L., Gerritsen, T., Gong, L., Heiner, D. C. Bray, P. F.: Metabolism of glycine in the non-ketotic form of hyperglycinemia. Pediat. Res. 2, 254 (1968)
Bachmann, C., Mihatsch, M. J., Baumgartner, R. E., Brechbühler, T., Bühler, U. K., Olafson, A., Ohnacher, H., Wick, H.: Nicht-ketotische Hyperglycinaemie: perakuter Verlauf im Neugeborenenalter. Helv. paediat. Acta 26, 228 (1971)
Balfe, J. W., Levison, H., Hanley, W. B., Jackson, S. H., Sass-Kortsak, A.: Hyperglycinuria in a newborn. Canad. med. Ass. J. 92, 347 (1965)
Baumgartner, R., Ando, T., Nyhan, W. L.: Non-ketotic hyperglycinemia. J. Pediat. 75, 1022 (1969)
Baumgartner, R., Scheidegger, S., Stalder, G., Hottinger, A.: Argininbernsteinsäurekrankheit des Neugeborenen mit letalem Verlauf. Helv. paediat. Acta 23, 77 (1968)
Boyd, E. In: Altmann, Dittmer, Hrsg., Growth, including reproduction and morphological development, S. 346. Biological handbooks. Washington: Federation of American Societies for Experimental Biology 1962
Carver, M. J., Paska, R.: Ion-exchange chromatography of urinary amino acids. Clin. chim. Acta 6, 721 (1961)
Childs, B., Nyhan, W. L., Borden, M., Bard, L., Cooke, R. E.: Idiopathic hyperglycinuria, a new disorder of amino acid metabolism. Pediatrics 27, 522 (1961)
Chou, S. M., Waisman, H. A.: Spongy degeneration of the central nervous system. Arch. Path. 79, 357 (1965)
Christensen, H. N., Cooper, P. F., Johnson, R. D., Jr., Lynch, E. L.: Glycine and alanine concentration of body fluids; experimental modification. J. biol. Chem. 168, 191 (1947)
Corbeel, L.: Congenital hyperglycinemia and hyperglycinuria. Ann. Meeting Europ. Soc. Pediat. Res., Athen, Juni 1966
Daniel, R. G., Waisman, H. A.: Adaption of the weanling rat to diets containing excess methionine. J. Nutr. 99, 299 (1969)
De Groot, C. J., Troelstra, J. A., Hommes, F. A.: Nonketotic hyperglycinemia. An in vitro study of the glycine-serine conversion in the liver of three patients and the effect of dietary methionine. Pediat. Res. 4, 238 (1970)
De Vries, A., Alexander, B.: Studies on amino acid metabolism—III. Plasma glycine concentration and hippuric acid formation following the ingestion of benzoate. J. clin. Invest. 27, 665 (1948)
Diezel, P. B.: Hyperglycinaemie (Glycinose) mit familiärer idiopathischer Hyperglycinurie. Verh. dtsch. Ges. Path. 48, 155 (1964)
Diezel, P. B., Martin, K.: Die Ahornsirupkrankheit mit familiärem Befall. Virchows Arch. path. Anat. 337, 425 (1964)
Diezel, P. B., Martin, K.: Hyperglycinaemie. Dtsch. med. Wschr. 91, 2249 (1966)
Donohue, W. L.: Lesions in the central nervous system associated with inborn errors of amino acid metabolism. Acta paediat. scand. 56, 116 (1967)
Efron, M. L., McPherson, T. C., Shih, V. E., Welsh, C. F., MacCready, R. A.: D-methioninuria due to DL-methionine ingestion. Amer. J. Dis. Child. 117, 104 (1969)
Ferdinand, W., Gordon, R. R., Owen, G.: Nonketotic hyperglycinemia. Clinical findings and aminoacid analysis of a new case. Clin. chim. Acta 30, 745 (1970)
Floyd, J. S., Fajan, A. S., Conn, J. W., Knopf, R. F., Rull, J.: Stimulation of insulin secretion by amino acids. J. clin. Invest. 45, 1487 (1966)
Freeman, J. M., Nicholson, J. F., Masland, W. S., Rowland, L. P., Carter, S.: Ammonia intoxication due to a congenital defect in urea synthesis. J. clin. Invest. 65, 1039 (1964)
Gerritsen, T., Kaveggia, E., Waisman, H. A.: A new type of idiopathic hyperglycinuria with hypo-oxaluria. Pediatrics 36, 882 (1965)
Gerritsen, T., Nyhan, W. L., Rehberg, M. L., Ando, T.: Metabolism of glyoxalate in nonketotic hyperglycinemia. Pediat. Res. 3, 269 (1969)
Goldstein, L. S.: The effect of supplementary DL-methionine on the growth of full-term infants. Arch. Pediat. 70, 285 (1953)
Holt, L. E., Snyderman, S. E.: Protein and amino acid requirements of infants and children. Nutr. Abstr. Rev. 35, 1 (1965)
Jonxis, J. H. P.: In: Brain damage by inborn errors of metabolism, S. 9, Haarlem: Bohn 1968
Jonxis, J. H. P., Hommes, F. A., de Groot, C.: The enzymatic defect of a non ketotic form of hyperglycinemia in two families and the results of the treatment with a diet without serine and glycine in three patients, members of these families. In: Bickel, H., Hudson, F. P., Woolf, L. I., Phenylketonuria, S. 307 ff. Stuttgart: Thieme 1971
Klavins, J. V., Kinney, T. D., Kaufmann, N.: Histopathologic changes in methionine excess. Arch. Path. 75, 99 (1963)
Levy, H. L., Shih, V. E., Madigan, P. M., Karolkevicz, V., Carr, J. R., Lum, A., Richards, A. A., Crawford, J. D., MacCready, R. A.: Hypermethioninemia with other hyperaminoacidemias. Studies in infants on high-protein diets. Amer. J. Dis. Child. 117, 96 (1969)
Linneweh, F., Willenbockel, U.: Zur diätetischen Therapie der Ahornsirupkrankheit (Leucinose). Mschr. Kinderheilk. 113, 420 (1965)
Mabry, C. C., Karam, E.: Idiopathic hyperglycinemia and hyperglycinuria. Sth. med. J. (Bgham, Ala.) 56, 1444 (1963)
Martin, J. J., Schlote, W.: Central nervous system lesions in disorders of aminoacid metabolism. A neuropathological study. J. neurol. Sci. 15, 49 (1972)
Menkes, J. H.: The pathogenesis of mental retardation in phenylketonuria and other inborn errors of amino acid metabolism. Pediatrics 39, 297 (1967)
Nyhan, W. L., Ando, T., Gerritsen, T.: Hyperglycinemia. In: Nyhan, W. L., Amino acid metabolism and genetic variation, S. 255 ff. New York: McGraw-Hill 1967
Prensky, A. L., Carr, S., Moser, H. W.: Development of myelin in inherited disorders of amino acid metabolism. Arch. Neurol. (Chic.) 19, 552 (1968)
Rampini, S., Vischer, D., Curtius, H. C., Anders, P. W., Tancredi, F., Frischknecht, W., Prader, A.: Hereditäre Hyperglycinaemie. Helv. paediat. Acta 22, 135 (1967)
Rushton, D. I.: Spongy degeneration of the white matter of the central nervous system associated with hyperglycinuria. J. clin. Path. 21, 456 (1968)
Sanchez, A., Swendseid, M. E.: Amino acid levels and enzyme activity in tissues of rats force-fed diets differing in methionine content. J. Nutr. 99, 145 (1969)
Schreier, K., Müller, W.: Idiopathische Hyperglycinaemie (Glycinose). Dtsch. med. Wschr. 37, 1739 (1964)
Similä, S., Visakorpi, J. K.: Clinical findings in three patients with nonketotic hyperglycinemia. Ann. Clin. Res. 2, 151 (1970)
Spackman, D. H., Stein, W. H., Moore, S.: Automatic recording apparatus for the use in the chromatography of amino acids. Anal. Chem. 30, 1190 (1958)
Stekol, J. A., Szaran, J.: Pathological effects of excessive methionine in the diet of growing rats. J. Nutr. 77, 81 (1962)
Ulrich, J.: Die cerebralen Entmarkungskrankheiten im Kindesalter. Diffuse Hirnsklerosen. Schriftenreihe Neurologie, Bd. 6, S. 88. Berlin-Heidelberg-New York: Springer 1971
Ziter, F. A., Bray, P. F., Madsen, J. A., Nyhan, W. L.: The clinical findings in a patient with nonketotic hyperglycinemia. Pediat. Res. 2, 250 (1968)
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Leupold, D., Przyrembel, H., Heymer, D. et al. Nichtketotische Hyperglycinämie. Z. Kinder-Heilk. 116, 95–114 (1974). https://doi.org/10.1007/BF00491509
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DOI: https://doi.org/10.1007/BF00491509