RESUMO
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.
Assuntos
Transtorno Autístico , Carnitina/deficiência , Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X/genética , Erros Inatos do Metabolismo , Oxigenases de Função Mista/genética , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Carnitina/biossíntese , Cognição/fisiologia , Éxons/genética , Deleção de Genes , Humanos , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Oxigenases de Função Mista/sangue , Oxigenases de Função Mista/urina , Penetrância , Fatores de Risco , IrmãosRESUMO
A best evidence topic in bariatric surgery was written according to a structured protocol. The question asked whether single-port laparoscopic sleeve gastrectomy produces better short-term perioperative outcomes compared to the conventional multi-port laparoscopic sleeve gastrectomy in the treatment of morbid obesity. A Pubmed search generated 82 papers, 6 of which represented the best evidence to answer the clinical question. Of the 6, 1 paper was an updated analysis of the same patient cohort. The evidence on this subject is good. Five papers were level III, nonrandomized studies, 2 of which were prospective and 3 were retrospective cohort studies. The sixth paper was a level II, randomized, prospective study. We conclude that single-port laparoscopic sleeve gastrectomy results in less use of postoperative analgesia and better cosmetic satisfaction compared to multi-port laparoscopic sleeve gastrectomy in the short-term. The two groups showed comparable results in terms of mean operative time, mean hospitalization, and percentage excess weight loss. There was no difference in rate of postoperative complications including trocar site incisional hernia, staple line leaks, and bleeding.