No abstract

Netherton syndrome is a rare genodermatosis characterized by ichthyosiform scaling, hair shaft abnormalities, and atopic features. Affected infants typically have delayed growth and development, immune abnormalities with recurrent infections, and intermittent aminoaciduria. We report a 23-day-old girl who presented with severe primary pulmonary hypertension, exfoliative erythroderma, and trichorrhexis invaginata. Genetic studies confirmed a premature termination mutation R350X in exon 12 of SPINK5. This mutation further supports the genotypic-phenotypic prediction that severe sequela result from premature termination mutations. To our knowledge, this is the first instance of Netherton syndrome associated with primary pulmonary hypertension to be reported. Further postulated is a possible link between excessive desquamation of fetal skin and respiratory failure in a neonate with Netherton syndrome.

Vacuum line kinetics studies have been made of the reaction in nitromethane between benzene and/or toluene, methoxyacetyl chloride (MAC), and AlCl(3) to produce benzyl or xylyl chlorides, CO, and a CH(3)OH(-)AlCl(3) complex. For both arenes, the rate law appears to be R = (k(3)/[AlCl(3)](0)) [AlCl(3)](2)[MAC]. When chloromethyl methyl ether (CMME) is substituted for MAC, a similar rate law is obtained. Both chloromethylation reactions yielded similar, large k(T)()/k(B)() ratios (500-600) and similar product isomer distributions with low meta percentages ( approximately 0.4) which suggest CH(3)OCH(2)(+) or the CH(3)OCH(2)(+)Al(2)Cl(7)(-) ion pair as a common, remarkably selective, electrophile. The kinetics of MAC decomposition to CMME and CO in the presence of AlCl(3) yielded the rate law R = k(2)[AlCl(3)](0)[MAC]. Here AlCl(3) is a catalyst (no CH(3)OH is formed), and thus the rate law is equivalent to the chloromethylation rate law. All three reactions have comparable reactivities, which is consistent with rate-determining production of the electrophile. Kinetics studies of benzene or toluene with SnCl(4) and MAC or CMME in dichloromethane were also completed. With MAC and benzene the rate law is R = k(3)[SnCl(4)](0)[MAC][benzene] and with toluene R = k(2)[SnCl(4)](0)[MAC]. MAC decomposition, again followed by CO production, was unaffected by the presence of either aromatic and obeyed the rate law R = k(2)' [SnCl(4)](0)[MAC] where k(2) approximately k(2)'. Chloromethylation with CMME followed the rate law R = k(3)[SnCl(4)](0)[CMME][arene] for benzene and toluene and produced a k(T)()/k(B)() ratio and product isomer distributions very similar to those determined with AlCl(3) in nitromethane, further supporting a common electrophile. Low-temperature (13)C and (119)Sn FT-NMR and Raman spectroscopic studies suggest the existence of a weak 1:1 adduct between MAC and SnCl(4) of the type RCXO --> SnCl(4), with electron donation to the metal through carboxy oxygen. Finally, an explanation is provided for the range of chloromethylation k(T)()/k(B)() values and product isomer percentages published in the literature.