ABSTRACT
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.
Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Brain Diseases, Metabolic/diagnosis , Glutaryl-CoA Dehydrogenase/deficiency , Outcome Assessment, Health Care , Amino Acid Metabolism, Inborn Errors/blood , Amino Acid Metabolism, Inborn Errors/genetics , Brain Diseases, Metabolic/blood , Brain Diseases, Metabolic/genetics , Carnitine/analogs & derivatives , Carnitine/blood , Delayed Diagnosis , Early Diagnosis , Female , Glutaryl-CoA Dehydrogenase/blood , Glutaryl-CoA Dehydrogenase/genetics , Glutaryl-CoA Dehydrogenase/metabolism , Humans , Infant, Newborn , Longitudinal Studies , Male , Mutation/genetics , Retrospective Studies , Tandem Mass Spectrometry , Time FactorsABSTRACT
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.
