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The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.
Guenzel, Adam J; Hall, Patricia L; Scott, Anna I; Lam, Christina; Chang, Irene J; Thies, Jenny; Ferreira, Carlos R; Pichurin, Pavel; Laxen, William; Raymond, Kimiyo; Gavrilov, Dimitar K; Oglesbee, Devin; Rinaldo, Piero; Matern, Dietrich; Tortorelli, Silvia.
Afiliação
  • Guenzel AJ; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Hall PL; Department of Human Genetics Emory University Atlanta Georgia USA.
  • Scott AI; Biochemical Genetics Laboratory Seattle Children's Hospital Seattle Washington USA.
  • Lam C; Division of Genetic Medicine, Department of Pediatrics University of Washington and Seattle Children's Hospital Seattle Washington USA.
  • Chang IJ; Division of Genetic Medicine, Department of Pediatrics University of Washington and Seattle Children's Hospital Seattle Washington USA.
  • Thies J; Division of Genetic Medicine, Department of Pediatrics University of Washington and Seattle Children's Hospital Seattle Washington USA.
  • Ferreira CR; National Human Genome Research Institute (NHGRI) Bethesda Maryland USA.
  • Pichurin P; Division of Clinical Genomics Mayo Clinic Rochester Minnesota USA.
  • Laxen W; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Raymond K; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Gavrilov DK; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Oglesbee D; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Rinaldo P; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Matern D; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
  • Tortorelli S; Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.
JIMD Rep ; 60(1): 67-74, 2021 Jul.
Article em En | MEDLINE | ID: mdl-34258142
BACKGROUND: Glutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical "low-excretor" (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation. METHODS: Samples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated. RESULTS: Five LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five GCDH variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype. CONCLUSIONS: The data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article