Maple syrup urine disease (MSUD) results from mutations affecting different subunits of the mitochondrial branched-chain ␣-ketoacid dehydrogenase complex. In this study, we identified seven novel mutations in MSUD patients from Israel. These include C219W-␣ (TGC to TGG) in the E1␣ subunit; H156Y-␤ (CAT to TAT), V69G-␤ (GTT to GGT), IVS 9 del[؊7:؊4], and 1109 ins 8bp (exon 10) in the E1␤ subunit; and H391R (CAC to CGC) and S133stop (TCA to TGA) affecting the E2 subunit of the branched-chain ␣-ketoacid dehydrogenase complex. Recombinant E1 proteins carrying the C219W-␣ or H156Y-␤ mutation show no catalytic activity with defective subunit assembly and reduced binding affinity for cofactor thiamin diphosphate. The mutant E1 harboring the V69G-␤ substitution cannot be expressed, suggesting aberrant folding caused by this mutation. These E1 mutations are ubiquitously associated with the classic phenotype in homozygous-affected patients. The H391R substitution in the E2 subunit abolishes the key catalytic residue that functions as a general base in the acyltransfer reaction, resulting in a completely inactive E2 component. However, wild-type E1 activity is enhanced by E1 binding to this full-length mutant E2 in vitro. We propose that the augmented E1 activity is responsible for robust thiamin responsiveness in homozygous patients carrying the H391R E2 mutation and that the presence of a full-length mutant E2 is diagnostic of this MSUD phenotype. The present results offer a structural and biochemical basis for these novel mutations and will facilitate DNA-based diagnosis for MSUD in the Israeli population. Maple syrup urine disease (MSUD)1 or branched-chain ␣-ketoaciduria is an autosomal recessive metabolic disorder caused by deficiency in the mitochondrial branched-chain ␣-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the oxidative decarboxylation (Reaction 1) of three branchedchain ␣-ketoacids (BCKAs) derived from branched-chain amino acids (BCAAs) leucine, isoleucine, and valine (1).

RSC and LSC are feasible procedures with acceptable complication rates. RSC enables operating more anatomically with less bleeding.

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Reported levels of pain and analgesic use during the first 24 h following robotic gynecologic surgery were significantly lower following general and spinal anesthesia compared to general anesthesia alone.