Lafora disease is not linked to the Unverricht-Lundborg locus.

Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

Thyroid status and muscle protein breakdown as assessed by urinary 3-methylhistidine excretion: study in thyrotoxic patients before and after treatment.

Urinary 3-methylhistidine (3MH) excretion was studied in nine thyrotoxic patients before and after treatment. Urinary creatinine (Cr) output was also measured and was low in the thyrotoxic subjects before treatment. Thus, although urinary output of 3MH was not greater than among the control population when expressed per subject, it was significantly elevated when expressed as the ratio of 3MH to Cr; this ratio fell significantly, reaching normal control values after a euthyroid state was obtained. In one patient who became hypothyroid, the 3MH/Cr ratio fell under the control value. There was a significant linear correlation between the 3MH/Cr ratio and the hormonal variables (T3, T4, FT4l); moreover, variations in the 3MH/Cr ratio and variations in the T3 level were closely correlated. 3-Methylhistidine appears to be a reliable index of muscular breakdown in thyrotoxicosis. From our results, it can be concluded, first of all, that hyperthyroidism is accompanied by an increased muscular catabolism, and, second, that the return to a euthyroid state results in an immediate normalization of muscular breakdown.

A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages.

OBJECTIVE: To evaluate the medical relevance of hyperhomocysteinemia in women with primary recurrent miscarriages. DESIGN: Case report and retrospective cross-sectional study. SETTING: Hematology outpatient department of a university hospital. PATIENT(S): Case report concerning a woman with five consecutive fetal losses. One hundred consecutive women with primary recurrent unexplained miscarriages (study group) and matched healthy controls (control group) with no antecedent fetal loss. INTERVENTION(S): Venous blood sample collection in resting individuals. MAIN OUTCOME MEASURE(S): Plasma total homocysteine concentrations, plasma folate concentrations, and DNA analysis for the C677T mutation of the 5,10 methylene tetrahydrofolate reductase gene. Normal threshold homocysteine concentration was obtained from values found in the control group (95th percentile). RESULT(S): The case patient was hyperhomocysteinemic, was homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene, and had plasma folate deficiency. Folic acid and pyridoxine administration normalized the homocysteine concentration and favored a successful pregnancy. In the retrospective study, 12 of 100 patients were hyperhomocysteinemic. Twenty percent had the C677T methylene tetrahydrofolate reductase genotype and 15% had low plasma folate concentrations. The highest values of homocysteine concentration were found in patients with both the C677T genotype and folate deficiency. CONCLUSION(S): Hyperhomocysteinemia should be identified in women with recurrent miscarriages because therapeutic normalization might permit a normal birth.

Uroporphyrinogen I synthase assay as an evaluation of the in vitro development of human BFU-E and CFU-E.

We describe a simple spectrophotometric microassay to quantify the proliferation and the differentiation of human bone marrow or blood erythroid progenitor cells CFU-E and BFU-E. These precursors give rise, in culture, to colonies and bursts with markedly variations in size and hemoglobinization, which cannot be accurately evaluated by the usual method of scoring. We then developed a sensitive biochemical microassay to measure the uroporphyrinogen I synthase activity of progenitors grown in small wells. This assay is a valuable index of erythroid differentiation in vitro. This method can offer the opportunity to test the efficiency in vitro of various therapeutic agents in patients with hemopoietic disorders.

Is hyperprolinemia type I actually a benign trait? Report of a case with severe neurologic involvement and vigabatrin intolerance.

Hyperprolinemia type I is a deficiency of proline oxidase (McKusick 23950), leading to hyperprolinemia and iminoglycinuria, usually with renal involvement. Hyperprolinemia type I is considered a benign trait. We reported a case of hyperprolinemia type I with a severe neurologic disorder and without renal involvement. The patient had marked psychomotor delay and right hemiparesis. Epilepsy was characterized by status epilepticus or a cluster of seizures. Laboratory findings revealed elevated levels of proline in the serum, urine, and cerebrospinal fluid without delta1-pyrroline 5-carboxylate dehydrogenase in the plasma or urine. Fluorescence in situ hybridization excluded a chromosome 22q11 deletion. Vigabatrin inhibits ornithine transaminase. Thus, vigabatrin could lead to a depletion of the normal pool of pyrroline 5-carboxylate dehydrogenase and could aggravate the clinical condition of the child. In this study, vigabatrin was discontinued. In the following months, the patient had marked psychomotor improvement, without modification of the epilepsy. We suggest that vigabatrin should be avoided in hyperprolinemia type I.

[Effect of the age and the sex on plasma concentration of amino acids]. / Effet de l'âge et du sexe sur les concentrations des acides aminés plasmatiques.

The effects of age and sex on the plasma free amino acid pattern of healthy men and women aged from 80 to 100 years were compared with those in younger adults (20 to 45 years old). Plasma amino acid concentrations were determined by ion-exchange chromatography on a 6300 Beckman analyzer. The plasma concentrations of valine, leucine, isoleucine, proline, glutamine + glutamic acid and phenylalanine were higher in males than in females. Citrulline, half-cystine, histidine, glutamine+glutamic acid, lysine, ornithine and phenylalanine plasma concentrations and the total plasma amino acids were higher in elderly than in younger subjects.

[Vascular complications of homocystinuria: a retrospective multicenter study]. / Les manifestations vasculaires de l'homocystinurie: étude rétrospective multicentrique.

PURPOSE: Arterial or venous thromboses are frequent in patients with homocystinuria. Because severe homocystinuria is rare, prevalence of thrombosis, especially in France, is still unknown. METHODS: Review of the clinical outcome of 37 patients with homocystinuria due to cystathionine-cystathionine beta-synthase deficiency (34) and 5,10-methylenetetrahydrofolate reductase (three) lead us to describe vascular complications occurring in 12 (32%) of them. RESULTS: Venous thromboembolism is the earlier and the most frequent one and is mainly found in untreated late-diagnosed cases. Under specific treatment of homocystinuria, thromboses are rare and always a complication of surgery associated with high thromboembolic risk. Association with factor V Leiden increased the risk of venous thrombosis.

[Urinary excretion of 3-methylhistidine. Value and application to the study of protein catabolism]. / L'excrétion urinaire de 3-méthylhistidine. Intérêt et application dans l'étude du catabolisme protidique.

The urinary excretion of 3-methylhistidine (3 MH) is considered an easy and reliable method to quantify muscle protein catabolism in man. The 3 MH/creatinine (Cr) ratio is thought to be a good index of fractional degradation of muscle fibre protein. In the present article, the stress is placed on the limitations of 3 MH assays an- on their clinical applications. In thyroid diseases and in malnutrition (anorexia nervosa), the 3 MH/Cr ratio differentiates clearly marasmic malnutrition without increase in protein catabolism from hypercatabolic states, such as hyperthyroidism, with excessive protein degradation. 3 MH measurements therefore appear to be useful to determine the contribution of protein catabolism to lean mass reduction.

[Transient symptomatic neonatal hyperammonemia]. / Hyperammoniémie néo-natale symptomatique transitoire.

Premature newborns suffering from respiratory distress and asphyxiated term newborns may present transient symptomatic neonatal hyperammonemia associated with reversible neonatal coma. As they survive they may develop normally; however the authors emphasize the importance of concomitant hemodynamic disorders and the extreme frequency of brain hemorrhage and ischemia. Ultrasonography or tomodensitometry are necessary for prognosis.