In order to enhance awareness and promote registry for inborn errors of metabolism (IEMs) in Egypt, we aimed to evaluate the prevalence and main clinical findings of IEMs detectable by tandem mass spectrometry (MS/MS) among high risk pediatric patients presenting to our tertiary care facility at Cairo University Children's Hospital over a period of 5years and to compare the disease burden in Egypt in the absence of a national screening program for inherited metabolic disorders with other populations. During this period 3380 Egyptian children were suspected of having IEMs based on clinical/laboratory presentation and were analyzed by MS/MS. Confirmatory testing was performed according to flagged analyte by MS/MS using a different sample type such as plasma or urine or by a different technique such as GC/MS. A relatively high number of patients (203/3380 (6%)) were confirmed with 17 different types of IEMs. Averages for age at diagnosis for different disorders ranged from 2.5months to 6.6years with general developmental delay and irreversible neurological damage being the most common presenting features (75.9% and 65.5%, respectively). Amino acid disorders (127/203 (62.6%)), mainly phenylketonuria (100/203 (49.3%)), were the most encountered, followed by organic acidemias (69/203 (34%)), while fatty acid oxidation defects (7/203 (3.4%)) were relatively rare. 88% of patients were born to consanguineous parents. The development of a nationwide screening program for IEMs is mandatory for early detection of these potentially treatable disorders, prompt and properly timed therapeutic intervention and prevention of the devastating neurological outcomes. •Tandem mass spectrometry is an essential tool for diagnosing IEMs in Egypt.•Metabolic disorders are relatively common in Egyptian children due to consanguinity.•203 children were diagnosed with 17 different IEMs out of 3380 high risk patients.•Aminoacidopathies especially PKU were the most encountered.•Nationwide expanded NBS by MS/MS is highly recommended for application in Egypt.