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The Catalonian Newborn Screening Program (CNSP) began in 1969, in Barcelona. It was promoted by Dr. Juan Sabater Tobella and supported by Barcelona Provincial Council and Juan March Foundation. That is how the Institute of Clinical Biochemistry was born, whose aims were diagnosis, research and teaching, along with the spirit of contributing to the prevention of mental retardation. The CNSP began with the detection of phenylketonuria (PKU), and, in 1982, the Program was expanded with the inclusion of congenital hypothyroidism detection. Towards 1990, the Program covered almost 100% of all newborns (NB) in Catalonia. In 1999, the CNSP was expanded with the incorporation of cystic fibrosis. It took fourteen years, until 2013, to make the largest expansion so far, with the incorporation of 19 metabolic diseases to the screening panel. The detection of sickle cell disease began in 2015 and in 2017 the detection of severe combined immunodeficiency was included. Currently, the CNSP includes 24 diseases in its main panel. Since 1969, 2,787,807 NBs have been screened, of whom 1,724 have been diagnosed with any of these diseases, and 252 of other disorders by differential diagnosis with those included in the main panel. The global prevalence is 1: 1,617 NBs affected by any of the diseases included in the CNSP and 1: 1,140 NBs if incidental findings diagnosed through the CNSP are included.

Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease is characterized by abnormal motor, respiratory, cognitive impairment, and autistic-like behaviors. No effective treatment of the disorder is available. Mecp2 knockout mice have a range of physiological and neurological abnormalities that resemble the human syndrome and can be used as a model to interrogate new therapies. Herein, we show that the combined administration of Levodopa and a Dopa-decarboxylase inhibitor in RTT mouse models is well tolerated, diminishes RTT-associated symptoms, and increases life span. The amelioration of RTT symptomatology is particularly significant in those features controlled by the dopaminergic pathway in the nigrostratium, such as mobility, tremor, and breathing. Most important, the improvement of the RTT phenotype upon use of the combined treatment is reflected at the cellular level by the development of neuronal dendritic growth. However, much work is required to extend the duration of the benefit of the described preclinical treatment.

Inborn errors of metabolism (IEM) are a group of diseases whose diagnosis is usually performed by quantification of several metabolites in biological fluids. The aim of this review is to report the role of the laboratory in IEM diagnosis, highlighting the methods available at present and their advantages and limitations. In conclusion, the huge number of recognized IEMs strongly advises the implementation of new high- output technologies in the laboratories devoted to IEM diagnosis. Although these technologies offer a high diagnostic ability, routine analyses are still very important, as well as consideration of several variables involved in biological sample collection and disease expression that may lead to misdiagnosis of IEMs.

Introduction: Oxidative stress may be implied in the pathogenic mechanisms of inborn errors of intermediary metabolism (IEIM)., Objective: The evaluation of the antioxidant status in IEIM by the measurement of erythrocyte antioxidant enzyme activities, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase and catalase., Patients and Methods: 34 patients with IEIM: 1) eleven with organic acidurias on protein restricted diet; 2) nine without special diet; 3) five patients with aminoacidopathies on protein restriction; 4) three patients with galactosemia and six with aminoacidopathies on protein free diet. Erythrocyte antioxidant enzymes were measured by spectrometric procedures adapted to the Cobas Fara II analyser., Results: SOD activity was significantly higher in groups 2 and 4 (p= 0.009, p= 0.001, respectively), and significantly lower in group 3 (p= 0.001) compared with age matched controls. SOD activity was significantly higher in the patients with IEIM on protein free diet (groups 2 and 4) compared with those on protein restricted diet (groups 1 and 3; p= 0.002) or with controls (p= 0.003). GPx activity was found significantly lower in group 1 patients (p= 0.004), and higher in group 2 (p= 0.029) compared with controls., Conclusions: 35% of the patients with IEIM had SOD activity above the control range, most of them with organic acidurias or homocystinuria, suggesting an induction of enzyme protein synthesis owing to an excess of free radical generation. The lower activities observed in patients on natural protein restriction may likely be due to a deficient bioavailability of antioxidant cofactors.

Aim: The etiology of cerebrovascular disease in the paediatric population, remains unknown in up to 40% of the cases ("idiopathic"), but recent advances could improve this percentage. We devised a comprehensive study protocol for such investigation aimed at the identification of potentially modifiable risk factors for paediatric stroke., Patients and Methods: From the 141 patients initially registered in our data base for stroke population (from January 1984 until December 1995), we invited all the patients with idiopathic cerebrovascular disease to complete the study protocol. New cases appeared from January 1996 until July 1999 were also included., Results: A total of 68 cases were identified. We found an etiology in 38% and in 76% of the cases we found at least one risk factor for stroke. Mild hyperhomocysteinemia was the most frequent risk factor identified (36% of patients versus 5% of controls), one of them an infant with fatal haemorrhagic infarct with classic homocystinuria. 31% of the patients had thrombotic risk factors (protein S, protein C, antithrombine III deficiency, factor V Leiden, etc). 17.6% had unspecific febrile illness at the time of the cerebral infarction and 11.6% had minor head injuries before the stroke., Conclusions: The use of the protocol improves the identification of potentially modifiable risk factors for stroke in childhood and may serve as a practical guideline for clinicians. The stroke protocol is as important as management strategies for acute stroke or for recurrence prevention, currently under consideration in the adult population.

Lipoprotein (a) has become of great interest as a biochemical marker for predicting the risk of developing cardiovascular alterations, with increased levels suggesting patients at a higher risk. We have realized a study of the plasma concentrations of lipoprotein (a) and other constituents of lipoprotein metabolism in children diagnosed with diabetes mellitus type I in relationship to the levels of metabolic control, the time of evolution of the disease and the presence or not of microalbuminuria (albumin in the urine greater than 30 micrograms/min). The study population was comprised of 211 children, between the ages of 3 and 18 years of age, divided into three groups according to the time of evolution of the disease: beginners (n = 15), time of evolution less than or equal to 5 years (n = 99) and more than 5 years (n = 92). All determinations were performed on specimens collected after 10 hours of fasting and before the morning dose of insulin. The following determinations were made: total cholesterol, triglycerides, cHDL, cLDL, cVLDL, Apo AI, Apo B, lipoprotein (a), albumin excretion rate (AER), glucose, fructose, glycosylated hemoglobin and creatinine clearance. We found significant differences between the groups in function of the existence of microalbuminuria and if the time of evolution of the disease exceeded 5 years. In conclusion, it appears that metabolic control does not influence the concentrations of lipoprotein (a), with an increased risk of cardiovascular alterations in those patients with a long disease evolution an those that have microalbuminuria.