Amino Acid Metabolism in Hereditary Fructosemia

Lindemann, Rolf; Gjessing, L. R.; Merton, Brita; Löken, Aagot Christie; Halvorsen, S

doi:10.1111/j.1651-2227.1970.tb08979.x

Cited by 20 publications

(2 citation statements)

References 13 publications

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“…We do not think it is possible to determine whether enzymatic defects or toxic substances are the cause of the deficiency in myelin observed in our patients. However, attention should be drawn to 1 case of fructosemia (10) where the pathological findings were quite similar to those presented in our 2 patients. Although the enzymatic defects are not identical, an interference with glial metabolism may have resulted in similar morphological picture.…”

Section: Acta Prediat Scand 60supporting

confidence: 84%

Fatal Congenital Lactic Acidosis in Two Siblings

et al. 1971

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Summary Two siblings have been described who developed a fatal metabolic acidosis during the first days of life. The acidosis was found to be caused by an accumulation of lactic acid in the second sibling. In the first sibling, no determination of lactic acid was performed, but the similarities in clinical, biochemical and pathological findings combine very strongly to suggest an identical condition. The children died at the age of 100 and 177 hours. The main pathological findings were confined to the brain, the thymus and the liver. Softening of the white matter was pronounced with delayed myelination. Organized bilateral paraventricular cystic spaces were found. Fatty changes were pronounced in the liver. In some respects these children differ from those previously reported with congenital lactic acidosis.

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Section: Acta Prediat Scand 60supporting

confidence: 84%

Fatal Congenital Lactic Acidosis in Two Siblings

et al. 1971

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“…A large excretion of the same metabolites has also been found in hereditary fructose intolerance (7).…”

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confidence: 73%

On the enzymic defects in hereditary tyrosinemia.

Lindblad¹,

Lindstedt²,

Steen³

1977

Proc. Natl. Acad. Sci. U.S.A.

430

268

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The activity of the enzyme porphobilinogen synthase (EC 4.2.1.24) in erythrocytes from patients with hereditary tyrosinemia was less than 5% of that in a control group and the activity in liver tissue was less than 1% of the reported normal activity. Urine from patients with hereditary tyrosinemia contained an inhibitor that was isolated and identified as succinylacetone (4,6-dioxoheptanoic acid) by gas/liquid chromatography-mass spectrometry. Fresh urine samples contained succinylacetoacetate (3,5-dioxooctanedioic acid) as well as succinylacetone. The inhibition of porphobilinogen synthase explains the high excretion of 5-aminolevulinate observed in hereditary tyrosinemia. Succinylacetone and succinylacetoacetate presumably originate from maleylacetoacetate or fumarylacetoacetate, or both, and their accumulation indicates a block at the fumarylacetoacetase (EC 3.7.1.2) step in the degradation of tyrosine. We suggest that the severe liver and kidney damage in hereditary tyrosinemia may be due to the accumulation of these tyrosine metabolites and that the primary enzyme defect in hereditary tyrosinemia may be decreased activity of fumarylacetoacetase.In the inborn error of metabolism called hereditary tyrosinemia, the main clinical findings are liver failure, which develops into liver cirrhosis in early childhood, and multiple renal tubular defects with hypophosphatemic rickets (1, 2). The derangement in tyrosine metabolism (i.e., hypertyrosinemia and high urinary excretion of 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate, and to a lesser extent 4-hydroxyphenylacetate) is due to a low activity of the enzyme 4-hydroxyphenylpyruvate dioxygenase [4-hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating), EC 1.13.11.27] (3), which catalyzes the formation of homogentisate (III) (Fig. 1) from 4-hydroxyphenylpyruvate (II).The increased excretion of these phenolic metabolites of tyrosine does not explain the liver and kidney damage in hereditary tyrosinemia because a similar large excretion has been found also in patients without liver and kidney disease-e.g., in a 5-year-old boy with multiple congenital anomalies and with negligible activity of soluble tyrosine aminotransferase (4) and in at least three other patients who were mentally retarded (2,5,6). A large excretion of the same metabolites has also been found in hereditary fructose intolerance (7).In 1967 we reported on a patient who had symptoms similar to those characteristic of acute intermittent porphyria (8). An increased excretion of 5-aminolevulinate has since then been observed in all patients studied by us, even in those without these symptoms (3, 9), but so far it has not been possible to find a biochemical link between the altered tyrosine metabolism and the increased excretion of a porphyrin precursor. In this report we present evidence for an enzyme defect in tyrosine catabolism in hereditary tyrosinemia that explains the increased excretion of 5-aminolevulinate. We also present a hypothesis

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Infantile Diffuse Cerebral Degeneration With Hepatic Cirrhosis

Huttenlocher¹,

Solitare²,

Adams³

1976

Archives of Neurology

119

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Four children had progressive degeneration of the cerebral cortex, with hepatic cirrhosis. They and four previously described ones, are representative of a distinct form of hepatocerebral degeneration. Onset of the neurological disorder is between ages 1 and 3 years, at times with mild developmental delay. Explosive onset of intractable convulsions, leaving the child in a stuporous and demented state, is characteristic. Generalized hypotonia or hemiparesis were observed in several affected children. Clinical evidences of hepatic disease, including ascites and jaundice, occurred late, if at all. The illness ended fatally within ten months of onset of convulsions. Pathological findings in the brain are neuronal loss and gliosis, in a pattern that is indistinguishable from that in degeneration of the cerebral gray matter in infancy (Alpers disease). The hepatic lesions consist of cirrhosis or of subacute hepatitis, with superimposed fatty infiltration of hepatocytes. The disorder is genetically determined, with recessive inheritance.

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Amino Acid Metabolism in Hereditary Fructosemia

Cited by 20 publications

References 13 publications

Fatal Congenital Lactic Acidosis in Two Siblings

Fatal Congenital Lactic Acidosis in Two Siblings

On the enzymic defects in hereditary tyrosinemia.

Infantile Diffuse Cerebral Degeneration With Hepatic Cirrhosis

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