The “Intoxication type” Inborn Errors of Metabolism (IT-IEM) encompass a group of inborn errors of intermediary metabolism that lead to acute or progressive intoxication from the accumulation of toxic compounds proximal to the metabolic block. This group includes the amino acid catabolism disorders (phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia, etc), organic acidurias (methylmalonic, propionic, isovaleric etc.), congenital urea cycle defects, carbohydtrates disorders (galactosemia, hereditary fructose intolerance), metal intoxication (Wilson, Menkes, hemochromatosis, and porphyrias), inherited in autosomal-recessive type. The IT-IEM share clinical similarities: do not interfere with embryo/fetal development, have a symptom-free interval and clinical signs of “intoxication”, affecting irreversible the nervous system. The symptoms such as lethargy, loss of appetite, vomiting, drowsiness, behavior troubles or exacerbation of pre-existing neurological problems (irritability, movement disorders, seizures) should put the doctor on alert for early diagnosis. Coma and mental retardation are the most severe complications on nervous system. Unsolved in 24h coma due to hyperammoniemia lead to irreversible severe neurological damage. The first-line investigations will provide the levels of ammonia, glucose, lactate, red blood count and blood gas, urine reducing substances. The second-line of plasma amino acids, acylcarnitines on dried blood spot, urinary organic acids and orotic acid should be urgently requested. Early-onset and late-onset clinical presentations may be observed. The early diagnosis is life-saving one, but the ultimate diagnosis is given by genetic investigation. Overall, treatment rests on four major principles: low protein diet, pharmacotherapy, extracorporeal detoxication and liver/kidney transplantation. Long-term follow-up should be provided by a multidisciplinary team of experts.