Numerous types of organic acidemias exist, with methylmalonic acidemia (MMA), propionic acidemia, and isovaleric acidemia among the most prevalent forms. Other forms of organic acidemias include maple syrup urine disease (MSUD), homocystinuria,

biotin-unresponsive 3-methylcrotonyl-CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency, ketothiolase deficiency, and glutaricacidemia type I (GA I). The typical clinical presentation is a toxic encephalopathy associated with vomiting, poor feeding, Selleckchem Buparlisib and neurologic symptoms such as seizures, abnormal tone, and lethargy that progresses to coma. In older children, variant forms of organic acidemias present with loss of intellectual function, ataxia or other focal neurologic signs, Reye syndrome, recurrent ketoacidosis, or psychiatric symptoms. Prolonged fasting, which can occur prior to anesthesia or diagnostic tests, can produce a catabolic state and precipitate a metabolic crisis. Therefore, elective hospitalizations or procedures that require the child with an organic acidemia to be fasted should be carefully planned with proper intravenous glucose support and metabolic

monitoring. In particular, children admitted to hospital awaiting LT may experience an unexpectedly prolonged period of fasting while the donor organ is procured and its quality is assessed. Strategies to monitor and manage the metabolic disease during this period should be in place.[316] LT may be indicated in patients with organic acidemia experiencing Selinexor frequent episodes of metabolic decompensation, uncontrollable hyperammonemia, restricted growth, or severe impairment of health-related 上海皓元 quality of life with conventional medical treatment.[114, 315] A collaborative discussion with specialized metabolic teams is critical. LT may not completely correct the metabolic defect. For example, in the case of MMA, serum levels of MMA and protein tolerance improve

following LT but do not normalize. Thus, MMA patients remain at risk for neurological deterioration and/or progressive renal insufficiency following LT.[317] In classic variant maple syrup urine disease (MSUD), a severe mitochondrial deficiency of the branch chain keto acid dehydrogenase (BCKDH) complex associated with volatile metabolic derangements with impaired brain development or unpredictable risk of neurologic crisis, the level of current metabolic control imparted by strict dietary management does not necessarily indicate protection against further episodes of metabolic decompensation.[318] Patients with classic variant MSUD defined by clinical phenotype of severe leucine intolerance (<15-30 mg/kg/day) have undergone LT successfully with elimination of dietary protein restriction and stabilization but without reversal of underlying neurocognitive deficits.