, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

The history of the Newborn Screening Program in Chile begins in 1984, when a pilot plan was developed that demonstrated the feasibility of its implementation. In 1992, the Ministry of Health started a national newborn screening program for phenylketonuria (PKU) and congenital hypothyroidism (CH), and in 1998, this was extended to the entire country. Throughout this period, a total of 2,478,123 newborns (NB) have been analyzed, obtaining initial coverage of 48.8%, which was later increased to 87.7%, and at present it is at 98.7% of all NB of our country. During this period, 131 cases with PKU have been diagnosed, resulting in an incidence of 1:18,916 NB, an average age of diagnosis of 18 ± 10.2 days and average phenylalanine level of 19,9 ± 8.8 mg/dl. In relation to CH, 783 cases have been confirmed, arriving at an incidence of 1:3,163 NB, with average age of diagnosis of 12.5 ± 6.9 days. Due to the good results of the program, the government is evaluating the initiation of an extended pilot program, to introduce other pathologies.

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Introduction: Propionic acidemia is a metabolic disease produced by a deficiency of the enzyme propionylCoA carboxylase. It can lead to coma, with severe neurologic encephalopathy or present later in life with vomiting, hypotonia, and seizures. An early diagnosis with adequate treatment helps to prevent the sequelae. Among the described complications is optic neuropathy, although not commonly reported, it is very disabling. Objectives: To describe two patients with propionic acidemia and optic neuropathy. Patients and Methods: Patient 1: 16 years old, male, parents without consanguinity. He was diagnosed at 5 months of age because of hypotonia and seizures. Until the age of 9 years, he evolved satisfactorily; therefore, he stopped treatment. At 13 years, he presented bilateral optic neuropathy. Patient 2: 20 years, female, parents without consanguinity. She was diagnosed with PA at 11 months of age because of hypotonia and seizures. She evolved satisfactorily until the age of 9 years when she presented a metabolic decompensation followed by a bad metabolic control. At 18 years, she presented bilateral progressive optic neuropathy. Results: Both patients have psychometric scores with borderline IQ 84-75 (WISC-R) beside optic neuropathy. They were evaluated by an ophthalmologist and also by neuroimaging (MRI of optic pathway). Conclusions: Pathophysiology of optic neuropathy is not completely understood. There is evidence that the damage is due to an accumulation of neurotoxic compounds secondary to the metabolic block increasing the oxidative stress. We suggest an annual ophthalmologic evaluation in the longterm follow-up of organic acidurias with visual loss, in order to detect this disabling sequela at an earlier stage.

Background:Mental retardation or intellectual disability affects 2% of the general population, but in 60% to 70% of cases the real cause of this retardation is not known. An early etiologic diagnosis of intellectual disability can lead to opportunities for improved educational interventions, reinforcing weak areas and providing a genetic counseling to the family. Aim: To search genetic diseases underlying intellectual disabilities of children attending a special education school. Material and methods: A clinical geneticist performed the history and physical examination in one hundred and three students aged between 5 and 24 years (51 males). A blood sample was obtained in 92 of them for a genetic screening that included a standard karyotype, fragile X molecular genetic testing, and search for inborn errors of metabolism by tandem mass spectrometry. Results: This approach yielded an etiological diagnosis in as much as 29 patients. Three percent of them had a fragile X syndrome. Inborn errors of metabolism were not detected. Conclusions: This type of screening should be done always in children with intellectual disability to establish an etiological diagnosis (Rev Méd Chile 2008; 136: 1542-51). (