title: Molecular picture of cobalamin C/D defects before and after newborn screening era.
abstract: Objective Birth prevalence of Cobalamin (Cbl) C or D defects in Portugal is an estimated 1:85,000, one of the highest worldwide. We compared the genotype/phenotype of patients identified with CblC or CblD before and after the implementation of expanded newborn screening. Methods Twenty-five Portuguese CblC/D patients, 14 symptomatic and 11 identified through screening, were diagnosed using gas chromatography or tandem mass spectrometry. Molecular characterization was performed through the study of MMACHC and MMADHC genes. Results The most common MMACHC mutation, c.271dupA, was present in 100% of MMACHC alleles of all CblC screened patients, in contrast with the 61% identified before expanded newborn screening. All studied cases (except one, who presented a CblD deficiency) presented a CblC defect. More CblC late-onset patients were diagnosed before the introduction of newborn screening than in the post newborn screening era, probably because some early onset patients died without a definitive diagnosis. Conclusion The molecular data found in this cohort contribute to the improvement of screening and diagnosis of Cbl defects and would enable a confirmatory diagnosis of these patients, reducing the need for complex, costly, laborious, and time-consuming biochemical/enzymatic tests.
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Nogueira
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Marcão
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Rocha
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Sousa
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Fonseca
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Valongo
authors.affiliation: Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Vilarinho
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D005006:Ethnicity; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008661:Metabolism, Inborn Errors / Q000453:epidemiology* / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D015997:Neonatal Screening; D010088:Oxidoreductases; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D058996:Quality Improvement; D014805:Vitamin B 12 / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527938:MMADHC protein, human; D033681:Mitochondrial Membrane Transport Proteins; C508359:MMACHC protein, human; D010088:Oxidoreductases; D014805:Vitamin B 12
keywords: Expanded newborn screening; MMACHC; MMADHC; Vitamin B12; blood spots; cobalamin