[Acrodermatitis enteropathica-like syndrome secondary to branched-chain amino acid deficiency during treatment of maple syrup urine disease]. / Pseudo-acrodermatite entéropathique secondaire à un déficit en acides aminés ramifiés au cours du traitement d'une leucinose.

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.

[Severe hyperhomocysteinemia revealing homocystinuria in two young adults with mild phenotype]. / Hyperhomocystéinémie sévère révélant une homocystinurie chez deux jeunes adultes présentant un phénotype peu marqué

INTRODUCTION: To the request of total plasma homocysteine determination in the investigation of vascular disease, diagnosis of homocystinuria in young adult patients with mild phenotype is not so rare. EXEGESIS: A 26-year-old man developed embolic cerebral infarction and a 22-year-old woman presented a right renal venous thrombosis one week after delivery. In each case, high concentration of total plasma homocysteine was first found and plasma and urinary amino acids analysis later on directed the diagnosis towards homocystinuria. Finally, reduced skin fibroblast cystathionine beta-synthase activity confirmed the diagnosis of homocystinuria. CONCLUSION: Total plasma homocysteine determination must be determined for screening for hyperhomocysteinemia in young adults with venous thromboembolism without characteristic phenotypic features of homocystinuria.

Necrotic tumor versus brain abscess: importance of amino acids detected at 1H MR spectroscopy--initial results.

PURPOSE: To assess the usefulness of the 0.9-ppm peak from amino acids (-CH3 moieties from valine, leucine, and isoleucine) for the differentiation of brain abscesses and tumors at in vivo hydrogen 1 magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Amino acid concentrations were determined in vitro in 13 purulent samples from brain and nonbrain tissues and in nine aseptic fluids from necrotic brain tumors at two-dimensional (2D) 1H MR spectroscopy and liquid chromatography. Thirty-four patients with cystic intracerebral mass lesions (28 tumors, six abscesses) were examined at 1H MR spectroscopy in vivo. RESULTS: Amino acids were identified in vitro in both purulent and aseptic samples. Amino acid concentrations measured in the aseptic fluids at both liquid chromatography and 2D MR spectroscopy were far below the detection threshold of in vivo 1H MR spectroscopy. Quantitative results obtained at 2D MR spectroscopy showed no overlap in the ranges of amino acid concentrations in purulent and aseptic samples. In vivo, the proton spectra obtained with a 136-msec echo time (TE) revealed amino acids (inverted peak at 0.9 ppm) in only the abscesses. CONCLUSION: The detection of amino acid resonance at 0.9 ppm at in vivo 1H MR spectroscopy (136-msec TE) is a promising tool for distinguishing bacterial abscesses and cystic brain tumors.

In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.

Isolated persistent hypermethioninemia.

New information has been obtained on 30 patients with isolated persistent hypermethioninemia, most of them previously unreported. Biopsies to confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of these patients. However, none showed the clinical findings or the extreme elevations of serum folate previously described in other patients with isolated hypermethioninemia considered not to have hepatic MAT deficiency. Patients ascertained on biochemical grounds had no neurological abnormalities, and 27/30 had IQs or Bayley development-index scores within normal limits or were judged to have normal mental development. Methionine transamination metabolites accumulated abnormally only when plasma methionine concentrations exceeded 300-350 microM and did so more markedly after 0.9 years of age. Data were obtained on urinary organic acids as well as plasma creatinine concentrations. Patterns of inheritance of isolated hypermethioninemia were variable. Considerations as to the optimal management of this group of patients are discussed.

[Hematotoxicity caused by azathioprine genetically determined and aggravated by xanthine oxidase deficiency in a patient following renal transplantation]. / Hématotoxicité de l'azathioprine à déterminisme génétique aggravée par un déficit en xanthine oxydase chez une transplantée rénale.

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.

Zinc changes in blood and urine during cyclic parenteral nutrition: relationships with amino acid metabolism.

Serum Zn, ultrafiltrable Zn and amino acids in serum and urine samples of twenty-seven patients receiving cyclic (12 h/24 h) parenteral nutrition were measured. These samples were collected in patients after a 12 h period of parenteral nutrition, and in the evening after 12 h without parenteral nutrition. The same determinations were performed in ten control subjects who followed the same sampling scheme. Total serum ultrafiltrable Zn showed no significant variations in the patients during parenteral nutrition, and was not significantly different in the two groups although the proportion of the Zn present in the ultrafiltrable fraction was elevated. Serum cystine levels were significantly higher (P = 0.05) in the patients than the control subjects, and cystine excretion was also higher in patients (P < 0.05) and increased after parenteral nutrition (56.0 (SE 6.5) v. 147.1 (SE 20.6) mumol/12 h; P < 0.001). Histidine levels did not vary significantly in serum after parenteral nutrition and were not different in the patients in comparison with the control subjects. Histidine excretion was not different in the two groups but increased significantly during parenteral nutrition (P < 0.05). Serum albumin was significantly depressed in the patients compared with the control subjects (45.3 (SE 1.5) v. 33.9 (SE 1.5) g/l; P < 0.001). These results suggest that cystine infusion and excretion relate to the changes occurring in serum Zn and in urinary Zn excretion.

Gas chromatographic-mass spectrometric determination of 5-hydroxymethyluracil in human urine by stable isotope dilution.

A method for the determination of 5-hydroxymethyluracil in urine is described. 5-Hydroxymethyluracil was extracted by reversed-phase chromatography and quantified by gas chromatography-mass spectrometry as tert.-butyldimethylsilyl derivative. Since natural 5-hydroxymethyluracil contained ca. 22% of M + 2 species, an internal standard consisting of [1,3-15N2,5-2H2]hydroxymethyluracil was used to correct losses during extraction, evaporation and derivatization. Between-run precision of this method was 7.79%, and concentrations as low as 1.87 nM could be measured. This sensitivity and precision could not be obtained with trimethylsilyl derivatives.

[Familial form of hypoglycemia due to leucine hypersensitivity]. / Forme familiale d'hypoglycémie par hypersensibilité à la leucine.

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.

[Rapid method for the determination of urinary oxalic acid by gas liquid chromatography (author's transl)]. / Méthode rapide de dosage de l'acide oxalique urinaire par chromatographie en phase gazeuse.

A rapid method for the determination of urinary oxalic acid by gas-liquid chromatography is described. The procedure involves extraction of oxalate from urine by tetrahydrofuran followed by evaporation to dryness and subsequent with diesterification with the boron-trifluoride propanol. The derivative is extracted with hexane and is detected by FID gas chromatography. Malonic acid is used as internal standard. Analytical recovery ranged from 94 to 105%. The coefficient of variation in replicate aliquots over the entire range is less than 6%. The expected range for our method is calculated to be 44 to 577 mumol of oxalate per 24-h urine.

[Study of the extraction of organic acids from urine. Preliminary step to their gas chromatographic separation (author's transl)]. / Etude de l'extrasction des acides organiques urinaires. Etape préalable à leur séparation en chromatographie en phase gazeuse.

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.

[Myocardial metabolism after one hour of anoxia and deep generalised hypothermia. Experimental study in the dog (author's transl)]. / Métabolisme du myocarde après une heure d'anoxie et hypothermie profonde généralisée. Etude expérimentale chez le chiot.

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.

Evaluation of myocardial metabolism after prolonged circulatory arrest and under profound hypothermia. An experimental study in young dogs.

15 young dogs between the ages of 2 and 4 months and weighing less than 6 kg underwent circulatory arrest for 1 h combined with profound hypothermia and extracorporeal circulation. During reperfusion, myocardial metabolism was studied by comparing the oxygen arteriovenous content difference and lactate balance at different temperatures. As the myocardial temperatures rose, the oxygen arterial venous difference increased from 4 vol/100 ml at 25 degrees C to 10 vol/100 ml; lactate balance changed from -19.3 to +8% which because of a large rise in arterial lactate indicates a considerable increase in lactate consumption. This study shows that profound and generalized hypothermia ensures good myocardial protection during at least 1 h of ishcemia and confirms results obtained with other forms of cardiac hypothermia.