{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:30:37Z","timestamp":1790105437611,"version":"4.0.1"},"reference-count":17,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder characterized by congenital and progressive microcephaly, severe developmental delay, epilepsy, and progressive cerebral atrophy. Therapeutic experience with L-asparagine supplementation remains limited and heterogeneous.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n \n We report a preterm female infant born to consanguineous parents who presented with congenital microcephaly and early-onset myoclonic epilepsy. During follow-up, diaphragmatic eventration was\u00a0identified and contributed to recurrent episodes of respiratory failure. Metabolic screening studies were unremarkable; however, cerebrospinal fluid asparagine concentration was markedly reduced (4.42\u202f\u03bcmol\/L; reference range 8\u201334\u202f\u03bcmol\/L). Brain magnetic resonance imaging demonstrated cerebral atrophy with white matter involvement. Whole-exome sequencing identified a homozygous splice-site variant in the\n ASNS<\/jats:italic>\n gene. Oral L-asparagine supplementation was initiated at 5\u00a0months of age (50\u202fmg\/kg\/day and increased to 100\u202fmg\/kg\/day after one week). A reduction in seizure frequency was observed following treatment initiation; however, this finding should be interpreted cautiously because it coincided with changes in antiepileptic therapy. No meaningful neurodevelopmental progress was observed during follow-up.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n ASNSD should be suspected in patients with progressive microcephaly and early-onset epilepsy despite normal metabolic screening, and CSF amino acid analysis is valuable for diagnosis. Although a reduction in seizure frequency was observed following L-asparagine supplementation in our patient, this finding should be interpreted cautiously because phenobarbital was discontinued and topiramate therapy was initiated during the same period. Therefore, the therapeutic efficacy of L-asparagine supplementation remains uncertain, and its impact on neurodevelopment appears limited.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2026-0234","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T06:56:12Z","timestamp":1786172172000},"source":"Crossref","is-referenced-by-count":1,"title":["Asparagine synthetase deficiency: clinical features and experience with asparagine supplementation"],"prefix":"10.1515","author":[{"given":"Tar\u0131k","family":"Y\u0131ld\u0131r\u0131m","sequence":"first","affiliation":[{"name":"Division of Pediatric Metabolic Diseases , Ba\u011fc\u0131lar Training and Research Hospital , Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7264-038X","authenticated-orcid":false,"given":"Arzu","family":"Selamio\u011flu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolic Diseases , Ba\u011fc\u0131lar Training and Research Hospital , Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryem Hilal","family":"Alta\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurologic Diseases , Ba\u011fc\u0131lar Training and Research Hospital , Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"\u00d6zel","sequence":"additional","affiliation":[{"name":"Department of Pediatric , Ba\u011fc\u0131lar Training and Research Hospital , Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Mete","sequence":"additional","affiliation":[{"name":"Department of Pediatric , Ba\u011fc\u0131lar Training and Research Hospital , Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026080806560858413_j_jpem-2026-0234_ref_001","doi-asserted-by":"crossref","unstructured":"Richards, NGJ, Kilberg, MS. 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