title: Glutaric aciduria type I: outcome of patients with early- versus late-diagnosis.
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.
authors: Unidad de Diagnóstico y Tratamiento de Enfermedades Congénitas del Metabolismo, Departamento de Pediatría, Hospital Clínico Universitario, Universidad de Santiago, Santiago de Compostela, Spain. maria.luz.couce.pico@sergas.es
authors: Ma Luz
authors: ML
authors: Couce
authors: Olalla
authors: O
authors: López-Suárez
authors: Ma Dolores
authors: MD
authors: Bóveda
authors: Daisy E
authors: DE
authors: Castiñeiras
authors: José A
authors: JA
authors: Cocho
authors: Judith
authors: J
authors: García-Villoria
authors: Manuel
authors: M
authors: Castro-Gago
authors: José Ma
authors: JM
authors: Fraga
authors: Antonia
authors: A
authors: Ribes
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D001928:Brain Diseases, Metabolic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D057210:Delayed Diagnosis; D042241:Early Diagnosis; D005260:Female; D050770:Glutaryl-CoA Dehydrogenase / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: C053168:glutarylcarnitine; D050770:Glutaryl-CoA Dehydrogenase; D002331:Carnitine