Homozygous FIBP nonsense variant responsible of syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities.

The acidic fibroblast growth factor (FGF) intracellular binding protein (FIBP) interacts directly with the fibroblast growth factor FGF1. Although FIBP is known to be implicated in the FGF signaling pathway, its precise function remains unclear. Gain-of-function variants in several FGF receptors (FGFRs) are implicated in a wide spectrum of growth disorders from achondroplasia to overgrowth syndromes. In a unique case from a consanguineous union presenting with overgrowth, macrocephaly, retinal coloboma, large thumbs, severe varicose veins and learning disabilities, exome sequencing identified a homozygous nonsense FIBP variant. The patient's fibroblasts exhibit FIBP cDNA degradation and an increased proliferation capacity compared with controls. The phenotype defines a new multiple congenital abnormalities (MCA) syndrome, overlapping with the heterogeneous group of overgrowth syndromes with macrocephaly. The different clinical features can be explained by the alteration of the FGFR pathway. Taken together, these results suggest the implication of FIBP in a new autosomal recessive MCA.

[Hemolytic anemia due to naphthalene poisoning]. / Anémie hémolytique par intoxication à la naphtaline.

INTRODUCTION: Naphthalene ingestion is a rare cause of hemolysis. CASE REPORT: We report a 33-year-old woman, originating from the Comoros, hospitalized for intense fatigue associated with delirium, fever and jaundice, three days after ritual ingestion of naphthalene. Biochemical parameters showed marked hemolysis. Outcome was favorable after red cells transfusion and hydratation with intravenous fluids. CONCLUSION: Diagnostic work-up of unexplained hemolysis should include the search for toxic exposition. Naphthalene poisoning can present with diagnostic challenge for physicians.

Characterization of triiodothyronine transport and accumulation in rat erythrocytes.

The transport of L-T3 was studied in washed rat erythrocytes. L-T3 uptake was temperature sensitive: the initial velocity of uptake at low substrate concentration was 40 times higher at 37 C than at 0C whereas, at equilibrium, the ratio of cell-associated to extracellular L-T3 was about 7 times lower at 37 C than at 0 C. When [125I]L-T3-loaded erythrocytes were diluted into a serum albumin-containing medium, the efflux of L-T3 proceeded at a rate similar to that of influx. A large excess of unlabeled L-T3 in the medium blocked influx and efflux of labeled L-T3, indicating a saturable carrier-mediated transport process across the plasma membrane. the transport obeyed simple Michaelis-Menten kinetics with an apparent Km of 53 nM and a Vmax of 4.3 pmol/min.10(8) cells at 0 C. The Km increased only slightly with temperature whereas the Vmax was 100 times higher at 37 than at 0 C. The Arrhenius activation energy of uptake was 21 Cal/mol. The nonsaturable adsorption of L-T3 to the cells did not exceed 1% of the equilibrium levels at 0 C and 10% at 37 C. Uptake of L-T3 was very specific: unlabeled L-T4, D-T3, triiodothyroacetic acid, rT3, and DL-thyronine inhibited uptake with inhibition constant (Ki) values which were 35, 60, 65, 110, and 250 times, respectively, greater than the Km of L-T3. [125I]L-T4 uptake was negligible. L-T3 uptake and L-T4 inhibition of L-T3 uptake were pH dependent. It is suggested that only the unionized 4'-OH forms of the hormones were recognized by the transport system. At equilibrium, L-T3 was accumulated within the cell (apparent intracellular concentration approximately 50 times higher than that in the medium at 37 C). However, uptake was not dependent on the transmembrane Na+ gradient, suggesting facilitated rather than active transport. Analysis of L-T3 binding to erythrocyte cytosolic proteins suggested that they were implicated in the intracellular trapping of L-T3. At a concentration of 5 x 10(9) erythrocytes/ml (approximately the blood concentration), the amount of L-T3 accumulated in the cells was 13.5 times higher than the extracellular amount. We conclude that L-T3 is solely transported by a saturable, stereospecific, and Na+-independent carrier system. The intracellular accumulation and the rapid transmembrane movements of L-T3 suggest that erythrocytes might play a role in the interorgan transport of L-T3.