title: Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis.
abstract: Maple syrup urine disease (MSUD) is a rare metabolic disorder for which the newborn screening (NBS) is possible but it has not been yet implemented for most Spanish regions. In the present study, we assess the clinical features and outcome of 14 MSUD Spanish patients with similar treatment protocol diagnosed either by NBS or by clinical symptoms. Eight patients were detected by NBS, four classic and four moderate MSUD. The average age at detection was 4.6 days, the mean plasmatic concentration of leucine at diagnosis was 1807 μM; the average number of days with leucine >1000 μM was 0.7 (0-4) and the mean number of total hospitalizations was 1.6 (0-5). Mean follow-up time was 70 months. They had good evolution: all remain asymptomatic, but 2 patients have attention deficit and hyperactivity disorder. Six patients with late diagnosis of classic MSUD were followed during 41 months. All presented with acute encephalopathy during the first month of life, mean leucine levels of 2355 μM, mean number of days with leucine >1000 μM of 6.6 (1-13) and mean number of total hospitalizations of 5.3 (4-7). Only two patients have a psychomotor development index in the lower limit (80 and 83). For all patients a good genotype-phenotype correlation was found and four novel mutations were identified: p.A311H, p.T84S, p.T397L, pL398P. Our study support that NBS improves prognosis of MSUD patients. But early diagnosis and an aggressive treatment together with a close monitoring of leucine levels improve neurological evolution in MSUD patients, even for those not detected by NBS.
authors.affiliation: Metabolic Unit, Servei of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, IDIS, CIBERER, ISCIII, Santiago de Compostela, Spain. Electronic address: maria.luz.couce.pico@sergas.es.
authors.forename: M L
authors.initials: ML
authors.lastname: Couce
authors.affiliation: Department of Neurology, Neurometabolic Unit, Hospital Sant Joan de Déu, and CIBERER, ISCIII, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Ramos
authors.affiliation: Metabolic and Dismorphology Unit, Department of Pediatrics, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Bueno
authors.affiliation: Gastroenterolgy, Nutrition and Metabolic Unit, Hospital Central de Asturias, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Díaz
authors.affiliation: Department of Gastroenterology and Nutrition, Metabolic Unit, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Meavilla
authors.affiliation: Metabolic Unit, Servei of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, IDIS, CIBERER, ISCIII, Santiago de Compostela, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Bóveda
authors.affiliation: Metabolic Unit, Servei of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, IDIS, CIBERER, ISCIII, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Marmiesse
authors.affiliation: Department of Neurology, Neurometabolic Unit, Hospital Sant Joan de Déu, and CIBERER, ISCIII, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Cazorla
mesh_terms: D001927:Brain Diseases / Q000453:epidemiology / Q000209:etiology; D002852:Chromatography, Ion Exchange; D057210:Delayed Diagnosis; D002658:Developmental Disabilities / Q000453:epidemiology / Q000209:etiology; D042241:Early Diagnosis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007231:Infant, Newborn; D007930:Leucine / Q000097:blood; D008297:Male; D008375:Maple Syrup Urine Disease / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011788:Quality of Life; D035583:Rare Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D013030:Spain; D053719:Tandem Mass Spectrometry
chemical_list: D007930:Leucine
keywords: Encephalopathy; Leucine; MSUD; Mood disorders; Newborn screening; Outcome