Mutation screening using sequencing analysis was performed. Quantitative Multiplex PCR of Short fluorescent Fragments analysis was developed for the detection of genomic microdeletions and microduplications. Splicing reporter minigene assay was used to evaluate the splicing effect on unclassified variants. 63 and 27 mutations have been identified in SLC3A1 and SLC7A9 genes respectively, of which 58 were novel. These mutations included 56 missense/nonsense, 13 deletion/insertion, 8 splicing, 13 large-scale rearrangements (18% of mutated alleles). Thus, 163 and 56 mutated alleles have been reported in SLC3A1 and SLC7A9 genes respectively. This report expands the spectrum of SLC3A1 and SLC7A9 mutations and supports that digenic inheritance is unlikely. Cystinosis is an AR lysosomal disorder. Free cystine accumulates continuously in lysosomes. Specific treatment with oral cysteamine results in long-term reduction of lylosomal cystine. However, corneal cystine crystals do not respond with oral cysteamine. A 26 years old female patient with typical nefro-cystinosis, had severe photophobia. The diagnosis was made on the first year of live and needs kidney transplant at 7 years of age. She developed epilepsy when she was 12 years. She has long been treated with oral Cystagon, which is not available in eydrops formulation. The Pharmacy Department of our Hospital have prepared and tested stability of cysteamine eydrops with the following formulation: cysteamine cloridrate 0,1136 g, sodic EDTA 0,1 g, benzalconium chloride 0,01 g and isotonic soluction of NaCl for 100,0 ml. This formulation is stable for 2 months and doesn't need refrigeration. The patient has now been treated with cysteamine eyedrops for 6 years. It is well tolerated and adherence to therapy is good. The severe photophobia disappeared. Ophthalmologic evaluation with confocal microscopy shows reduction on density corneal cystine crystals density. This cysteamine eyedrops formulation, used in this patient no needs refrigeration, is stable for a long period and most importantly, it is well tolerated and efficient. Most of the inborn errors of metabolism (IEM) are autosomal recessively inherited. Rarely, more than one IEM are seen in the siblings of one family or in the same sibling. Here we report a patient with both argininosuccinic aciduria (ASA) and methylmalonic acidemia (MMA) and our therapeutic approach. Chronic management of both diseases consist of a low-protein diet. But the treatment of more than one disorders affecting aminoacid metabolism was challenging. A 2 -day-old male patient was admitted to our hospital since a previous sibling had been diagnosed with ASA. The first child of the family had died due to MMA but the family refused prenatal diagnosis in this pregnancy. Laboratory investigations of the patient revealed elevated C3 propionyl carnitine, citrulline and argininosuccinic acid levels on serum tandem MS, elevated methylmalonic acid on urinary organic acid analysis and increased argininosuccinic acid levels on urine tandem MS. Both ASA and MMAwere diagnosed. The dietary regimen of the patient was planned with MMA being the basis and all the replacement therapies were given both for ASA and MMA. When 4 months old, his metabolic status was well, plasma ammonia level and blood gases were normal and he had no ketosis. Male infant presented at 8 weeks with respiratory difficulties and encephalopathy, a respiratory alkalosis, hyperammonaemia (355 μmol/l). Investigations revealed raised plasma ornithine (632 μmol/l) but no orotic acid or homocitrulline in his urine. Treatment with arginine, benzoate and phenylbutyrate resulted in rapid recovery. OAT deficiency was confirmed by enzyme and molecular studies. On treatment his ornithine increased to over 1000 μmol/l. Arginine supplements were discontinued at 11 weeks of age. However after a further 3 weeks ornithine had fallen to 10 μmol/l, and glutamine increased to >1000 μmol/l with ammonia at 144 μmol/l. Arginine supplements were therefore restarted at 4 months. Within a short period there was again a marked increase in ornithine to 983 μmol/l and so supplements were stopped. By 7 months his glutamine had increased to >900 μmol/l and ornithine fell to 31 μmol/l so arginine was again restarted. At 12 months his ornithine showed a persistent increase to so that arginine was stopped. Since then there has been no fall in ornithine levels or increase in glutamine. This case demonstrated that flux through the ornithine synthetic/catabolic pathway can reverse repeatedly in the first year of life so infants with OAT deficiency remain at risk from hyperammonaemia. Background: The outcome of childhood acute lymphoblastic leukemia has improved substantially after introduction of Asparaginase. Pegylated asparaginase (PEG-Asparaginase) has a longer half life and has been introduced recently to optimize therapeutic efficacy. We investigated whether introduction of PEG-Asparaginase affected the risk of hyperammonemia, an infrequent side effect of asparaginase treatment. Patients and methods: We analyzed blood samples and clinical data of eight consecutive patients with acute lymphoblastic leukemia receiving PEG-asparaginase in our hospital. Results: Maximum ammonia levels ranged from 89 to 400 μmol/L. Symptoms varied from mild anorexia and nausea to headache, vomiting, dizziness and lethargy and led to interruption of PEG-asparaginase in three patients. Analysis of plasma amino acid concentrations during PEGasparaginase therapy revealed a depletion of asparagine (6/6) and a marked reduction in glutamine concentration (5/6), in conjunction with strongly increased concentrations of both aspartic acid and glutaminic acid. Urea cycle intermediates were normal. Conclusions: Peg-asparaginase was associated with symptomatic hyperammonemia in all patients, unlike previous reports. We propose that the ammonia produced through hydrolysis of aspargine and glutamine is largely responsible for the hyperammonemia in patients receiving Peg-asparaginase. Background: L-Asparaginase is commonly used in chemotherapy protocols for lymphoproliferative disorders. Asparagine is an essential amino acid for tumor cells and required for their rapid malignant growth. The mechanism of tumor lysis of l-Asparaginase is hydrolysis through of the amido group of asparagine to aspartate and ammonia. L-Asparaginase has been reported to cause hyperammonemia, which theoretically may be induced by increased ammonia production exceeding the capacity to detoxify and/or decreased detoxification capacity. Case reports: A retrospective chart study was performed in 4 female patients, who were evaluated for encephalopathy caused by hyperammonemia after l-Asparaginase, PEG-Asparaginase or Erwinase (all incorporating l-Asparaginase). Extensive metabolic (blood amino acid profile, urine organic acids, and urine orotic acid) and molecular studies failed to identify a specific inborn error of metabolism Background: Ornithine Transcarbamylase (OTC) deficiency is a heterogeneous X-linked disorder comprising severe neonatal-onset hyperammonaemic encephalopathy and variable later-onset disorders. Case presentation: A developmentally normal 18 month boy presented with seizures, acute encephalopathy and elevated ammonia 115 μmol/L (10-50). CSF glutamine was 1085 μmol/L (319-742) and arginine was 7 μmol/L (12-30) with increased urinary orotate. His mother was asymptomatic.