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Introduction: Clinical pictures resembling acrodermatitis enteropathica have been described in acquired zinc deficiency and deficiencies of other nutrients such as biotin, essential fatty acids and amino acids as well as biotin metabolism disorders. We describe the case of an infant with maple syrup urine disease who developed an acrodermatitis-like syndrome due to iatrogenic valine and isoleucine deficiency., Case-Report: A diagnosis of maple syrup urine disease was made in a 5-month-old infant girl with severe neurologic disorders with extremely high levels of the three branched-chain amino acids (leucine, valine and isoleucine) in plasma and urine. Seven days after the start of therapy with a diet excluding these branched-chain amino acids, plasma isoleucine and valine concentrations were low while plasma leucine remained elevated. At the same time, a periorificial and acral dermatitis appeared together with diarrhea. Serum zinc concentrations were normal. A diagnosis of acrodermatitis enteropathica-like syndrome secondary to isoleucine and valine deficiency was suspected. Valine and isoleucine supplementation resulted in rapid resolution of the eruption., Discussion: Several cases of acrodermatitis enteropathica-like eruptions resulting from therapeutic protein restriction diets have been described in infants with different aminoacidopathies. The accompanying dermatosis was associated with a raised plasma leucine/isoleucine ratio and/or isoleucine deficiency, or valine deficiency. While the exact pathogenesis of the skin lesions has not been established, these observations show that branched-chain amino acids are essential for normal growth and differentiation of keratinocytes. The essential role of isoleucine is further substantiated by the fact that its presence is critical in keratinocyte culture media, with growth arrest occurring upon its depletion.

Azathioprine is an immunosuppressor used with ciclosporin and corticosteroids after organ transplantation. Azathioprine is rapidly transformed into 6-mercaptopurine which in turn is metabolized by three competitive pathways: a) intracellular hypoxanthine guanine phosphoribosyl transferase leads to 6-thioguanine nucleotides which can damage chromosome DNA; b) thiopurine methyltransferase produces inactive methylated derivatives; c) xanthine oxidase produces thiouric acid. Due to inter-individual variations in the later two pathways, azathioprine dose must be adapted to each patient. A 48-year-old female patient underwent renal transplantation in 1994 and was given immunosuppressive therapy combining thymoglobulins, azathioprine and ciclosporin. Severe leukopenia (< 3000/mm3) occurred on day 5 requiring withdrawal of azathioprine. Known hypouricaemia (< 50 mumol/l) suggested xanthine oxidase deficiency. Laboratory results confirmed xanthine oxidase deficiency and also revealed reduced thiopurine methyltransferase activity (14.9 pmol/h/mg Hb). Azathioprine toxicity was confirmed by regression of the leukopenia after withdrawal and recurrence at rechallenge. Xanthine oxidase deficiency occurs in 2% of the general population. Reduced thiopurine methyltransferase activity affects 11% of the population. The combined presence of these two genetic anomalies led to early and sudden intolerance to azathioprine and emphasize the need to develop new immunosuppressor agents degraded by other metabolic pathways.

The authors report on a boy and his mother showing signs of hypoglycemia due to hypersensitivity to leucine that is related to a that dominant autosomal. The cyclic inheritance glycemia test shows hyperinsulism; oral as well as intravenous loading dose of leucine tests showed that this hyperinsulism is due to hypersensitivity to leucine. The clinical picture, outcome of the disease dietary and medical treatment with diazoxide, and the role of GIP in insulin secretion is discussed.

Ten organic acids are extracted from urine. Two extraction methods are used: anion exchange on DEAE-Sephadex columns and organic solvent extraction with five different solvents: diethyl ether, ethyl acetate, isopropyl chloride, light petroleum, and tetrahydrofuran. In order to quantify the extractions, the corresponding 14C-labeled acids are added to standard acid solutions and extraction rates are measured by a liquid scintillation counting system. The results show that: (1) The efficiency of anion exchange is generally good for all tested acids. (2) The extraction efficiency is not identical for the different solvents, one solvent being more efficient for a certain acid than another: tetrahydrofuran, which is generally a good solvent, is too hygroscopic to be usable. Isopropyl chloride and light petroleum are too specific with the most apolar molecules. Ethyl acetate and diethyl ether are similar and usable because of their acceptable solubilisation power as to the most polar molecules, their good solubilisation reproducibility and their readiness of use. (3) The solvent extraction method is not as time-consuming as the anion-exchange method which generally requires lengthy elution and extraction.

Fifteen young dogs weighing less than six kilograms underwent circulatory arrest for one hour and profound hypothermia with extra-corporeal circulation. During reperfusion, myocardial metabolism was studied by comparing the oxygen arterio-venus (02 A-V) difference and lactate consumption at different temperatures. As the myocardial temperature rose, 02 A-V difference increased from 4 vl/100 cc at 25 degrees C to 10 vol/100 cc and K1 lactate balance rose from -19,3% to + 8% which indicates a large increase in lactate consumption. This study shows that profound and generalized hypothermia ensures good myocardial protection during at least one hour of ischemia. This experimental study confirms results obtained with other forms of cardiac hypothermia.