Table 1.
Current therapeutic concepts for patients with branched-chain amino/keto acid metabolic defects
| General/specific | Well-established long-term management (see special literature for a detailed description of emergency treatment) | Individualised treatment, transplantation and experimental approaches (including animal data) |
| General | Continuous (long-term) monitoring; combined therapeutic approaches, multidisciplinary care | Antioxidants and essential fatty acids (particularly if low) |
| Prevention of metabolic crises, maintenance of an anabolic state, adequate or high energy diet supplied as carbohydrate and fat to support anabolism | Development of novel, mitochondria-targeted antioxidants | |
| Stimulation of residual activity of deficient enzymes by using their cofactors (in responsive cases) | Competitors for transport of the particular amino acids into the brain | |
| Substrate reduction/protein modified-diet/low-protein diet with disease-specific amino acid supplements (formulas) deficient in the particular precursor amino acids and enriched with micronutrients | Supplementation with alternative energy sources/preservation of cellular energy supply (e.g., creatine, ornithine alpha- ketoglutarate) | |
| Continuous feeding or tube feeding to assure adequate caloric intake if needed | ||
| Reduction of toxic metabolites by using adjunctive medications or procedures if applicable (including even hemodialysis, e.g. in case of hyperammonemic coma) | ||
| Symptomatic treatment during illnesses (e.g., parenteral nutrition, specific drug therapy) | ||
| Treatment of special organ complications (such as renal disease in MMA etc.) | ||
| MSUD | Thiamine in thiamine-responsive MSUD; substitution of valine und isoleucine (according to the individual needs) | Phenylbutyrate (in milder MSUD phenotypes); transplantation of liver/hepatocytes; norleucine |
| MMA | Hydroxocobalamin (usually not cyanocobalamin) in cobalamin-responsive MMA; L-carnitine; intermittent intestinal decontamination, e.g. with non-absorbed antibiotics (to reduce the production of propionate by gut bacteria) | Liver and/or kidney transplantations; growth hormone therapy (limited experience) gene therapy |
| PA | Biotin in biotin-responsive PA; L-carnitine; Intermittent intestinal decontamination, e.g. with non-absorbed antibiotics (to reduce the production of propionate by gut bacteria) | Liver transplantation; gene therapy |
| IVA | L-carnitine; L- glycine (in severe IVA phenotypes) |