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Early diagnosis of adenylosuccinate lyase deficiency using a high‐throughput screening method and a trial of oral S ‐adenosyl‐ l ‐methionine as a treatment method
Author(s) -
Werkhoven Michiel A,
Duley John A,
McGown Ivan,
Munce Teresa,
Freeman Jeremy L,
Pitt James J
Publication year - 2013
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.12244
Subject(s) - purine metabolism , urine , newborn screening , hypotonia , metabolite , chemistry , medicine , pharmacology , biochemistry , enzyme
Aim The aim of this study was to develop a high‐throughput urine screening technique for adenylosuccinate lyase ( ADSL ) deficiency and to evaluate S ‐adenosyl‐ l ‐methionine ( SAM e) as a potential treatment for this disorder. Method Testing for succinyladenosine (S‐Ado), a marker of ADSL deficiency, was incorporated into a screening panel for urine biomarkers for inborn errors of metabolism using electrospray tandem mass spectrometry. Liquid chromatography–mass spectrometry and high‐performance liquid chromatography were used to confirm and monitor the response of metabolites to oral SAM e treatment. Results Increased levels of S‐Ado were detected in a 3‐month‐old male infant with hypotonia and seizures. ADSL gene sequencing revealed a previously described c.–49T>C mutation and a novel c.889_891dup AAT mutation, which was likely to disrupt enzyme function. After 9 months of SAM e treatment, there was no clear response evidenced in urine metabolite levels or clinical parameters. Interpretation These results demonstrate proof of the principle for the high‐throughput urine screening technique, allowing earlier diagnosis of patients with ADSL deficiency. However, early treatment with SAM e does not appear to be effective in ADSL deficiency. It is suggested that although SAM e treatment may ameliorate purine nucleotide deficiency, it cannot correct metabolic syndromes in which a toxic nucleotide is present, in this case presumed to be succinylaminoimidazole carboxamide ribotide.