3-Methylglutaconic aciduria type I redefined A syndrome with late-onset leukoencephalopathy

Objective: 3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. It is thought to present in childhood with nonspecific symptoms; it was even speculated to be a non-disease. The natural course of disease is unknown. Methods: This is a study on 10 patients with 3-methylglutaconic aciduria type I. We present the clinical, neuroradiologic, biochemical, and genetic details on 2 new adult-onset patients and follow-up data on 2 patients from the literature. Results: Two unrelated patients with the characteristic biochemical findings of 3-methylglutaconic aciduria type I presented in adulthood with progressive ataxia. One patient additionally had optic atrophy, the other spasticity and dementia. Three novel mutations were found in conserved regions of the AUH gene. In both patients, MRI revealed extensive white matter disease. Follow-up MRI in a 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in deep white matter. Conclusion: We define 3-methylglutaconic aciduria type I as an inborn error of metabolism with slowly progressive leukoencephalopathy clinically presenting in adulthood. In contrast to the nonspecific findings in pediatric cases, the clinical and neuroradiologic pattern in adult patients is highly characteristic. White matter abnormalities may already develop in the first decades of life. The variable features found in affected children may be coincidental. Long-term follow-up in children is essential to learn more about the natural course of this presumably slowly progressive disease. Dietary treatment with leucine restriction may be considered. Neurology (R) 2010;75:1079-108

In-hospital Delay of Appendectomy in Acute, Complicated Appendicitis

Background: Present theory is that uncomplicated and complicated appendicitis are different entities. Recent studies suggest it is safe to delay surgery in patients with uncomplicated appendicitis. We hypothesize that patients with complicated appendicitis are at higher risk for postoperative complications when surgery is delayed. Methods: Data was used from the multicenter, prospective SNAPSHOT appendicitis study of 1975 patients undergoing surgery for suspected appendicitis. Adult patients (≥ 18 years) who underwent appendectomy for appendicitis were included in this study. The primary outcome was the difference in postoperative complications between patients with complicated appendicitis who were operated within and after 8 h after hospital presentation. Secondary outcomes were the incidence of both uncomplicated and complicated appendicitis in relationship to delay of appendectomy. Follow-up was 30 days. A multivariable analysis was performed. Results: Of 1341 adult patients with appendicitis, 34.3% had complicated appendicitis. In patients with complicated appendicitis, 22.8% developed a postoperative complication compared to 8.2% for uncomplicated appendicitis (P 8 h) increased the complication rate in patients with complicated appendicitis (28.1%) compared to surgery within 8 h (18.3%; P = 0.01). Multivariate analysis showed a delay in surgery as an independent predictor for a postoperative complication in patients with complicated appendicitis (OR 1.71; 95%CI 1.01–2.68, P = 0.02). Conclusion: In-hospital delay of surgery (> 8 h) in patients with complicated appendicitis is associated with a higher risk of a postoperative complication. It is important that we recognize and treat these patients early