Klein J 1 , Weinhold N 1 , Hennermann JB 1 1 Charité Universitätsmedizin Berlin, Berlin, Germany New therapeutic options, e.g. cPMP substitution in molybdenum cofactor deficiency type A (MoCD), raised interest in early detection of affected infants with inherited defects of purine and pyrimidine metabolism. Established methods of selective screening, e.g. HPLC with UV-or MS/ MS detection, use urine as matrix, not a common material in newborn material. In addition the cycle times are not suitable for high throughput screening. Therefore, a flow injection-MS/MS method with negative electrospray ionization was developed for fast screening of purines and pyrimidines in dried blood spots (DBS). The identical sample preparation for analysing amino acids and acylcarnitines in DBS can be used for determination of purines and pyrimidines, too. Analysis of purines includes the measurement of xanthine, uric acid, and sulfocysteine for MoCD, analysis of pyrimidines includes the measurement of orotic acid, ureidopropionic and ureidoisobutyric acid for urea cycle disorders. Thus, a single extract can be used for simultaneous measurement of amino acids, acylcarnitines, purines and pyrimidines in DBS. This approach allows the inclusion of purine and pyrimidine disorders into the newborn screening panel without extensive additional efforts. cPMP: cyclic Pyranopterinmonophosphate Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood. Here, we report findings in a neonate who was evaluated because of a positive family history of OAT deficiency. The reversed enzymatic flux in early infancy resulted in borderline low ornithine concentrations-evoking urea cycle disturbances-an increased proline and low plasma citrulline concentration. Consequently, the proline/citrulline ratio was increased compared to controls. To find out whether newbornscreening (NBS) is suitable to detect this disorder, we performed aminoacid analysis on the original dried blood spot (from NBS) and compared it with >450.000 NBS data documented in the Minnesota database. The proline concentration (777 μmol/L) was just above the 99%ile (776 μmol/L), and citrulline concentration (4.5 μmol/L) was just above the 1%ile (4.37 μmol). The proline/citrulline ratio (172.9) was far above the 99% ile (97.6). Applying this ratio to NBS will lead to early and specific detection of neonatal OAT deficiency, with no additional expense for NBS laboratories quantifying aminoacids. Additional NBS samples from proven OAT deficient patients are required to provide disease reference ranges. Individuals with hereditary tyrosinemia type I(HT-1) are homozygous for one of several fumarylacetoacetate hydrolase (FAH)-mutations and are gradually deficient for the enzyme activity. As a result, the precursors of FAH accumulate and are metabolised to succinylacetone (SUAC).These precursors and SUAC have toxic effects. Affected individuals show hepatic and renal diseases and also neurologic manifestations. Untreated, the disease might lead to premature death. HT-1 has a general incidence of 1:100,000 with a higher occurrence in particular ethnic groups. Using general elevated tyrosine concentration as a marker for HT-1 has limited value because it is also common for tyrosinemia type II and III and other liver diseases. However, an increase in SUAC is pathognomonic for HT-1. The objective of this study was to evaluate a validated commercial LC-MS/ MS-test assaying newborn blood spots for SUAC among other markers for inborn errors of metabolism. Dried blood spots of 5,000 newborns were screened using the new method based on a simple extraction and derivatisation step. We compared the results with those obtained in parallel using our own in-house LC-MS/MS-method established at the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna. Our data showed that the new method reliably identified all patients with HT-1. Background: Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. Two of these defects cblC/D defects can cause combined methylmalonic-aciduria and homocystinuria.