Successful domino liver transplantation in maple syrup urine disease using a related living donor

Maple syrup urine disease (MSUD) is an autosomal recessive disease associated with high levels of branched-chain amino acids. Children with MSUD can present severe neurological damage, but liver transplantation (LT) allows the patient to resume a normal diet and avoid further neurological damage. The use of living related donors has been controversial because parents are obligatory heterozygotes. We report a case of a 2-year-old child with MSUD who underwent a living donor LT. The donor was the patient's mother, and his liver was then used as a domino graft. The postoperative course was uneventful in all three subjects. DNA analysis performed after the transplantation (sequencing of the coding regions of BCKDHA, BCKDHB, and DBT genes) showed that the MSUD patient was heterozygous for a pathogenic mutation in the BCKDHB gene. This mutation was not found in his mother, who is an obligatory carrier for MSUD according to the family history and, as expected, presented both normal clinical phenotype and levels of branched-chain amino acids. In conclusion, our data suggest that the use of a related donor in LT for MSUD was effective, and the liver of the MSUD patient was successfully used in domino transplantation. Routine donor genotyping may not be feasible, because the test is not widely available, and, most importantly, the disease is associated with both the presence of allelic and locus heterogeneity. Further studies with this population of patients are required to expand the use of related donors in MSUD.

Automated, simplified GC/MS data processing system for organic acidemia screening and its application.

Gas chromatography mass spectrometry (GC/MS) is widely used in diagnosis of organic acidemias. However, GC/MS has not yet become a routine laboratory test, because of the complexity in interpretation of GC/MS data. We developed a personal computer-based system of automated metabolic profiling and disease detection for the screening of organic acidemias by GC/MS. The data were processed after the GC/MS analysis of urinary organic acids. In this system, 130 kinds of metabolites and 25 disorders of organic acids were enrolled for the search and detection, respectively. Metabolites were identified with methylene unit values (MU). target ions (Q- and C-ions) and their intensity ratios, and semiquantified by peak relative area (%) of the Q-ions to that of an internal standard. Metabolites whose values exceeded the cutoff of the control table were flagged as abnormal. The diseases or pathological condition were automatically evaluated by combination of the abnormal compounds. In this system, index metabolites were categorized into three groups. "AND, "OR" and "NO". The groups, "AND" and "OR" comprised essential and optional compounds, respectively, for the specific diagnosis. The third group, "NO", included compounds which must be absent to reach a diagnosis. We compiled data of MU values and mass spectrum of 130 kinds of index metabolites, and tested the usefulness of this system by analysis of 74 patients with 19 kinds of diseases. In all cases, at least a correct diagnosis could be found among the disease names outputted. We have successfully applied this to a pilot neonatal screening by GC/MS in our regional area, and acylglycine analysis by the stable isotope dilution method with tert-butyldimethylsilyl derivatization. With our system, many people can attend for screening programs using GC/MS.