In urine samples of the boy, his older brother with the same clinical phenotype and their mother neurotransmitter metabolites were analysed for determination of the metabolic phenotype. As expected the neurotransmitter metabolite profile in the index patient was characteristically abnormal and confirmed the functional deficiency. Aminoglycosides and other compounds can promote premature stop codon (PTC) readthrough constituting a potential therapy for patients with nonsense mutations. Using an in vitro transcription-translation system we have established the proof of principle that nonsense mutations in the PCCA and PCCB genes causing propionic acidemia can be partially suppressed by aminoglycosides, with different efficiencies depending on the sequence context. To correct the metabolic defect, the amino acid incorporated at the PTC (usually Gln or Trp), should support protein function and this has been evaluated for 5 PCCA and 7 PCCB nonsense mutations in silico and by in vitro expression analysis of the predicted missense changes. Most missense changes retain partial activity confirming the feasibility of the approach. In selected patients' fibroblasts cultured for 5 days with different amounts of G418 and gentamycin we observe a significant increase (4-5 fold) Background: Cobalamin C (Cbl-C) defect is the most common inborn error of cobalamin metabolism causing methylmalonic aciduria and homocystinuria. Despite pharmacological treatment with OH-cbl, betaine, folate, and carnitine, the long-term outcome is unsatisfactory with progression of neurological and visual impairment. The pathophysiological mechanism(s) causing brain and ocular damage still remains to be elucidated. Recently, the contribution of oxidative stress has been hypothesized based on in vitro studies showing in Cbl-C fibroblasts a significant ROS increase that can be corrected by adding OH-cbl to cell culture (Richard, Hum Mutat 2009) . Objective: Since reduced glutathione plays an important role in ROS detoxification, we assessed in vivo by reverse-phase HPLC the glutathione status in blood cells obtained from 13 treated Cbl-C patients.