Excretion of Orotic Acid and Orotidine in Heterozygotes of Congenital Orotic Aciduria

Lotz, Myron; Fallon, Harold J.; Smith, Lloyd H.

doi:10.1038/197194a0

Cited by 32 publications

(11 citation statements)

References 7 publications

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“…Normal human urine contains trace amounts of OA [17] and, as previously reported by us [8] and confirmed in this work, the compound is quantifiable at sub-micromolar level also in plasma and blood of unaffected patients.…”

Section: Discussionsupporting

confidence: 64%

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography–tandem mass spectrometry

D’Apolito

Garofalo

Marca

et al. 2012

Journal of Chromatography B

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Section: Discussionsupporting

confidence: 64%

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography–tandem mass spectrometry

D’Apolito

Garofalo

Marca

et al. 2012

Journal of Chromatography B

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“…An "Operon" Disease ?-The results obtained in this case appear to confirm an apparent exception to the one gene/one enzyme hypothesis (Smith and Lotz, 1963). Recent hypotheses concerning the control of enzyme activity offer the theoretical possibility that the basis of the disease could be deletion of a single "operator" gene controlling the defective enzyme sequence (Jacob and Monod, 1961 ;Monod et al, 1963).…”

Section: Other Biochemical Investigationssupporting

confidence: 70%

“…J., 1965, i, 547-552 Although orotic acid is an important precursor in the synthesis of pyrimidines (Figs. 1 and 6), only minute amounts are founds in normal blood and urine (Smith and Baker, 1959 ;Lotz et al, 1963). The urinary excretion of large amounts of orotic acid was first reported by Huguley et al (1959), occurring in a male child with a refractory megaloblastic anaemia.…”

Section: Examination Of Candidatesmentioning

confidence: 97%

“…Acquired Orotic Aciduria.-The antineoplastic agent 6-azauridine is a specific competitive inhibitor of orotidylic decarboxylase and produces an acquired and reversible orotic aciduria Lotz et al, 1963). Elves et al (1963) examined the chromosomes of dividing leucocytes from patients treated with 6-azauridine and observed a number of abnormal " globule " chromosomes which, it was suggested, were due to faulty synthesis of nucleic acids.…”

Section: Other Biochemical Investigationsmentioning

confidence: 99%

See 1 more Smart Citation

Hereditary Orotic Aciduria and Megaloblastic Anaemia: A Second Case, with Response to Uridine

Becroft¹,

Phillips²

1965

BMJ

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Examination of CandidatesAfter the resident has completed his training programme he is ready to apply for examination by the board in the specialty in which he is interested. In general, the conduct of examination by all boards is largely the same. Many divide their examinations into a Part I and a Part II. Usually the former is a written examination and the latter is oral. In most instances the essay type of examination has been abandoned in favour of one in which there are multiple choices. Thus answers can be brief-the " true-or-false type of examination." This type of examination is more expeditious ; it permits reports to be completed more quickly; grading is more nearly accurate, and testing can be more extensive. As a rule the candidate becomes eligible for his oral examination after he has passed the " written." The oral examination varies with the requirements and needs of various specialties. It is important because it is the last obstacle to be surmounted before the candidate is certified.Members of specialty boards are conscientious, honest, dedicated persons who contribute freely of their time and effort, often at great sacrifice, to advance the standards of their specialty, without thought of personal aggrandizement or recompense for their services. Like members of the faculty of a great university sitting at a defence of a doctoral dissertation, they are imbued with a sense of their responsibility to determine the competence of candidates who appear voluntarily before them for certification as diplomates.Aside from setting up minimal standards which must be met before candidates can appear for examination before a board, such a board performs no function in the educational programme available for training future diplomates. It is the function of a specialty examining board to determine competence only and to certify those who possess it to a sufficient degree to warrant approbation. Somewhat like the dissociation between the judicial and the legislative branches of a modern democracy, a specialty examining board scrupulously avoids participation in that phase of the educational programme which aims at development of competency. Similarly, like a judicial body in and of itself, a specialty board has neither the will nor the authority to prevent the practice of any specialty by a licensed physician, regardless of his ability or lack of it. The chief objective of all specialty examining boards is to elevate and to maintain the standards of specialty practice, and the finite manifestation of their efforts toward this objective is the certificate of competence which they issue to all physicians who can meet minimal requirements of licensure and graduate medical education.

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“…Although it is not clear why orotic acid accumulates rather than other products of the de nouo pyrimidine pathway, two explanations are possible: (I) work with rat hepatoma cells has shown that addition of uridine to the culture medium rapidly represses the levels of orotidine pyrophosphorylase in these cells [9]; (2) rat liver orotidine decarboxylase is inhibited by uridine because of a feedback effect on pyrophosphorylase than on decarboxylase. Asymptomatic orotic aciduria has also been found in heterozygotes of congenital orotic aciduria [17], patients receiving 6-azauridine [17,311 and allopurinol [31], normal pregnant women [31], and in some patients receiving parenteral nutrition [281.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and Genetic Studies of a Family with Ornithine Transcarbamylase Deficiency

et al. 1974

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ExtractW e have described a patient with ornithine transcarbamylase (OTC) deficiency.T h e clinical course and pedigree substantiate the X-linked transmission of the defect with varying degrees of illness in females. Because orotic aciduria accompanied hyperammonemia in the patient, orotic acid was measured as an indication of a partial OTC deficiency after ammonia and protein loading in members of the patient's family. Both the mother, a n obligate carrier, and an aunt, the only symptomatic female in this pedigree, had hyperammonemia after the ingestion of ammonium chloride. They also had significant orotic aciduria after a protein load as did the two female cousins whose ammonium tolerance was normal. T h e maternal grandmother excreted a large amount of orotic acid in her urine relatively consistently. 'These data suggest that the two female cousins and the maternal grandmother are asymptomatic female heterozygotes despite their normal ammonium loading tests. SpeculationProtein loading in the form of a relatively palatable and innocuous meal, followed by determination of orotic acid content in urine, may prove to be a sensitive, noninvasive, and easy means to identify female carriers of ornithine transcarbamylase deficiency.

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Excretion of Orotic Acid and Orotidine in Heterozygotes of Congenital Orotic Aciduria

Cited by 32 publications

References 7 publications

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography–tandem mass spectrometry

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography–tandem mass spectrometry

Hereditary Orotic Aciduria and Megaloblastic Anaemia: A Second Case, with Response to Uridine

Metabolic and Genetic Studies of a Family with Ornithine Transcarbamylase Deficiency

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