| Title: |
REVEAL-CP: Selective Screening of Pediatric Patients for Aromatic L-Amino Acid Decarboxylase Deficiency with a Guthrie Card and In Silico Structural Modeling of One Index Case |
| Authors: |
Strehle, Eugen-Matthias; Battini, Roberta; Gowda, Vasantha; Kuster, Alice; Amin, Sam; Bertoldi, Mariarita; Perduca, Massimiliano; Leuzzi, Vincenzo; Johnson, Shelley; Lupo, Paul; Liu, Emelline; Fox, Emily; Werner, Christian |
| Contributors: |
Strehle, Eugen-Matthia; Battini, Roberta; Gowda, Vasantha; Kuster, Alice; Amin, Sam; Bertoldi, Mariarita; Perduca, Massimiliano; Leuzzi, Vincenzo; Johnson, Shelley; Lupo, Paul; Liu, Emelline; Fox, Emily; Werner, Christian |
| Publication Year: |
2025 |
| Collection: |
Università degli Studi di Verona: Catalogo dei Prodotti della Ricerca (IRIS) |
| Subject Terms: |
3-OMD; AADC deficiency; DDC; p.Ser250Phe; structural modeling |
| Description: |
Background: The main objective of this prospective, multicenter study (REVEAL-CP) was to test children with cerebral palsy-like signs and symptoms for raised 3-O-methyldopa (3-OMD) blood levels, a biomarker for aromatic L-amino acid decarboxylase deficiency (AADCd). A secondary objective was to characterize the molecular basis for the defective aromatic L-amino acid decarboxylase (AADC) gene product. Methods: Patients were identified in pediatric secondary and tertiary care hospitals through database searches and personal communication. 3-OMD concentrations from Guthrie card tests were determined using liquid chromatography/mass spectrometry. If 3-OMD was raised, cerebrospinal fluid analysis and dopa decarboxylase (DDC) gene sequencing were performed. An in-silico mutagenesis analysis was carried out to model altered AADC enzymes. Results: In total, 166 patients were enrolled in this study. The median age was 8 years. Sixty-six patients (39.8%) had a diagnosis of cerebral palsy, with the most common type being "mixed" (n = 42; 25.3%). One patient (0.6%), an 11-month-old boy from Italy, was diagnosed with AADCd caused by a homozygous, pathogenic DDC variant (c.749C>T; p.Ser250Phe). Three-dimensional modeling of the Ser250Phe AADC enzyme variant revealed its destabilization. Conclusions: A Guthrie card test for 3-OMD is a recognized screening technique for AADCd. If universal newborn screening for this metabolic disease is not available, children with signs and symptoms of a movement disorder should be investigated for AADCd. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39841990; info:eu-repo/semantics/altIdentifier/wos/WOS:001405889600003; volume:29; issue:1; firstpage:12; lastpage:18; numberofpages:7; journal:GENETIC TESTING AND MOLECULAR BIOMARKERS; https://hdl.handle.net/11562/1152351; https://doi.org/10.1089/gtmb.2024.0427 |
| DOI: |
10.1089/gtmb.2024.0427 |
| Availability: |
https://hdl.handle.net/11562/1152351; https://doi.org/10.1089/gtmb.2024.0427 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.95B4BC54 |
| Database: |
BASE |