Refractory Megaloblastic Anemia Associated with Excretion of Orotic Acid

Huguley, Charles M.; Bain, James A.; Rivers, Shirley L.; Scoggins, Robert B.

doi:10.1182/blood.v14.6.615.615

Cited by 145 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inborn errors of purine and pyrimidine metabolism were first reported in children as the cause of kidney stones and refractory anaemia in 1954 and 1959, respectively (Dent and Philpot 1954;Huguley et al 1959). In the 1970s an association was described between gout and hypoxanthine-guanine phosphoribosyltransferase deficiency, between adenosine deaminase and severe combined immunodeficiency, and between purine nucleoside phosphorylase deficiency and T-cell specific dysfunction (Ochs et al 1973;Rijksen et al 1987;Wadman et al 1977).…”

Section: Historymentioning

confidence: 99%

Inborn errors of purine and pyrimidine metabolism

Jurecka

2009

J of Inher Metab Disea

View full text Add to dashboard Cite

Genetic disorders of purine and pyrimidine (PP) metabolism are under-reported and infrequently mentioned in the general literature, as well as in reviews dedicated to other inborn errors of metabolism. Owing to limited awareness, relatively recent recognition, as well as considerable phenotypic variation, these disorders may often be misdiagnosed or remain undiagnosed. Disorders that arise as a result of dysfunction in PP metabolism represent some of the most challenging diagnostic problems in medicine. In addition to their low prevalence rates, they also present with extremely variable signs and symptoms. They may affect any system in a variety of manners, and often mimic other, more recognizable disorders. The diagnostic problem is compounded by the fact that some biochemically affected patients are symptom-free. Rapidly evolving laboratory techniques such as high-performance liquid chromatography coupled to tandem mass spectrometry are now well established as the preferred method for detection for these defects, but currently the most important step in diagnosis consists of suspecting the disorder. Diagnosis is vital because genetic counselling can be provided and, in some cases, specific treatment can be offered that may slow or even reverse clinical symptoms. If undiagnosed, these disorders can be devastating to patients and their families, resulting in early death or institutionalization for the rest of patient's life. This article describes the current state of knowledge about inborn errors of purine and pyrimidine metabolism, focusing on the varying clinical presentations, the laboratory findings and discusses indications for selective screening for these disorders.

show abstract

Section: Historymentioning

confidence: 99%

Inborn errors of purine and pyrimidine metabolism

Jurecka

2009

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…However, the bone marrow morphology and cytogenetic findings were initially quite confusing. Myeloproliferative disorders [8], Orotic aciduria [9,10], dihydrofolate reductase deficiency 191, glutamate formiminotransferase deficiency [ 121, other inborn errors of folate met abolism [9], and thiamine responsive megaloblastic anemia [ 131 can give a very similar picture. Normal serum vitamin B,, and serum red cell folate levels excluded the possibility of a dietary cause of her clinical symptoms.…”

Section: Iiiscussionmentioning

confidence: 99%

Transcobalamin II deficiency associated with unusual bone marrow findings and chromosomal abnormalities

et al. 1983

View full text Add to dashboard Cite

A female infant presented at seven weeks of age with failure to thrive, progressively severe pancytopenia, hypogammaglobulinemia and, mucosal ulceration. Bone marrow morphology showed severed megaloblastic changes in the myeloid series with a shift to the left and an increased number of blasts with abnormal morphology. Erythroid precursors and megakaryocytes were markedly decreased. Cytogenetic studies showed marked aneuploidy and increased chromosomal breakage. Treatment with high doses of vitamin B12 resulted in a dramatic clinical response with hematological values becoming normal. The patient's serum showed absence of transcobalamin II, and very little TC I and TC III binding. The patient's parents had only half the lower limits of normal transcobalamin II. QUSO G-32 was used for separation of transcobalamins, and the results were confirmed by Sephacryl S-300. This case illustrates the usefulness of QUSO in the rapid diagnosis of transcobalamin II deficiency.

show abstract

“…In this connec tion our own patient was not a case of vitamin B6 deficiency because of no increased excretion of xanthurenic acid into urine following oral dose of trypto phan (see above). In 1959 Huguley et al 15 reported an infant with a refractory megaloblastic anemia associated with orotic acid excretion, and they stated that the refractory megaloblastic anemia of that infant was caused by a failure in the pyrimidine nucleotide synthesis due to a block at the stage of conversion of orotic acid to orotidylic acid. In our own patient orotic acid was unable to be detected on chromatographic analysis of urine specimens, but uracil, UMP and UDP were demonstrated in urine (see below).…”

Section: Autopsy Findingsmentioning

confidence: 99%

Uracil-uric Refractory Anemia with Peroxidase Negative Neutrophils

Arakawa

Wada

Hayashi

et al. 1965

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

A peculiar disorder of a 7 year-4 month -old girl is described which is charac terized by 1) a refractory hypochromic anemia with megaloblastic bone marrow of a slight degree, 2) an occurrence of the neutrophils which are negative to all the stains for peroxidase, oxidase, Sudan-black B and succinic dehydrogenase, 3) a urinary output of uracil, UMP and UDP, and 4) fatal outcome due to sepsis with leukemoid blood picture. A term "Uracil-uric Refractory Anemia with Peroxidase Negative Neutrophils" is suggested for this new disorder.The purpose of the present paper is to describe a 7 year-4 month-old girl with a peculiar disorder which is characterized by 1) a refractory hypochromic anemia with a slight megaloblastic change in the bone marrow , 2) an occurrence of the neutrophils which are negative to all the stains for peroxidase , oxidase, Sudanblack B and succinic dehydrogenase, 3) urinary excretion of uracil , UMP and UDP, and 4) fatal outcome due to sepsis with leukemoid blood picture .

show abstract

Refractory Megaloblastic Anemia Associated with Excretion of Orotic Acid

Cited by 145 publications

References 11 publications

Inborn errors of purine and pyrimidine metabolism

Inborn errors of purine and pyrimidine metabolism

Transcobalamin II deficiency associated with unusual bone marrow findings and chromosomal abnormalities

Uracil-uric Refractory Anemia with Peroxidase Negative Neutrophils

Contact Info

Product

Resources

About