Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme.

Newborn screening (NBS) by tandem mass spectrometry started in Galicia (Spain) in 2000. We analyse the results of screening and clinical follow-up of inborn errors of metabolism (IEM) detected during 10 years. Our programme basically includes the disorders recommended by the American College of Medical Genetics. Since 2002, blood and urine samples have been collected from every newborn on the 3rd day of life; before then, samples were collected between the 5th and 8th days. Newborns who show abnormal results are referred to the clinical unit for diagnosis and treatment. In these 10 years, NBS has led directly to the identification of 137 IEM cases (one per 2060 newborns, if 35 cases of benign hyperphenylalaninemia are excluded). In addition, 33 false positive results and 10 cases of transitory elevation of biomarkers were identified (making the positive predictive rate 76.11%), and 4 false negative results. The use of urine samples contributed significantly to IEM detection in 44% of cases. Clinical symptoms appeared before positive screening results in nine patients (6.6%), four of them screened between days 5 and 8. The death rate was 2.92%; of the survivors, 95.5% were asymptomatic after a mean observation period of 54 months, and only two had an intellectual/psychomotor development score less than 85. Compared to other studies, a high incidence of type I glutaric aciduria was detected, one in 35,027 newborns. This report highlights the benefits of urine sample collection during screening, and it is the first study on expanded newborn screening results in Spain.

Inborn errors of metabolism in a neonatology unit: impact and long-term results.

BACKGROUND: Inborn errors of metabolism (IEM) have greater repercussions in neonatology units. The goal of our study was to evaluate the impact of IEM in a neonatology unit and the outcome of these neonates. METHODS: All patients with IEM admitted in our unit were evaluated during an 8-year period for specific diagnosis, clinical features, therapy and long-term neurodevelopment. RESULTS: The study group was comprised of 31 infants, 18 of which required admission to the neonatal intensive care unit (NICU) (1.63% of income) due to severe symptoms. Twenty-two of the 31 had an earlier diagnosis and treatment due to expanded newborn screening, made from the third day of life. The most frequent diagnosis in the NICU, representing 66.66% (12/18), was diseases that cause an endogenous intoxication. Despite the diagnosis by tandem mass spectrometry, many of these patients had severe clinical symptoms prior to the screening results. Aggressive support was often necessary (extracorporeal removal therapy, mechanical ventilation). Death occurred generally in the first year of life (5/6). The death rate in the NICU was 10.3%. The survivors presented higher scores on the Psychomotor Development Index if the diagnosis of the disease was either made or helped by screening. This also depends on the type of disease. CONCLUSION: Earlier diagnosis by expanded newborn screening and earlier treatment is essential in order to be able to prevent neurological sequelae.

Glutaric aciduria type I: outcome of patients with early- versus late-diagnosis.

Patients with Glutaric aciduria type 1 (GA-1) can be identified by newborn screening using tandem mass spectrometry. The clinical evolution of screened patients seems to be more favourable compared with those diagnosed later, although long-term evolution is still doubtful. We have evaluated the outcome in nine GA-1 patients diagnosed in our region during 12 years. Six were detected by newborn screening and 3 clinically. The birth prevalence was 1:35,027. High blood C5DC concentration, in 8/9 patients, was found, whereas all patients exhibited high concentration of this metabolite in urine. Therefore, urine C5DC was a good marker for the detection of this disease. Eight different mutations in the GCDH gene were identified, four of them were novel (p.R88H, p.Y398C, p.R372K, p.D220N); being p.R227P the mostcommon. Macrocephaly with enlarged frontotemporal subarachnoid space was present in 4/6 patients diagnosed by newborn screening, all these patients required high energy intake, and in two cases, enteral feeding during the first year of life was needed. One child had an intercurrent episode of feeding refuse with hypoglycemia at two years of age. The mean follow-up time of screened patients was 56 months, and patients still remain asymptomatic. However, after a mean follow-up of 97 months treatment efficacy was poor in unscreened patients, two of them showing a severe spastic tetraparesis. Plasma levels of lysine, tryptophan and carnitine, were the most useful biomarkers for the follow-up. Our data support that, early diagnosis and treatment strategies are essential measures for the good clinical evolution of GA-1 patients.