Asparajin Sentetaz Eksikliği: Yeni Bir ASNS Varyantı ve Klinik Fenotiplerin Sistematik Gözden Geçirilmesi ile Serebrospinal Sıvı Asparajin Seviyeleri

Özet (abstract)

Background: Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder associated with microcephaly, severe developmental impairment, epilepsy, and progressive cerebral atrophy. Reduced cerebrospinal fluid (CSF) asparagine has been proposed as a supportive biochemical marker, but the extent to which it provides useful diagnostic information remains uncertain. Methods: We report a female patient with molecularly confirmed ASNSD and conduct a systematic review of molecularly confirmed cases in accordance with PRISMA 2020. PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched from inception to 20 September 2026. Clinical, survival, neuroimaging, molecular, and CSF-asparagine data were extracted for individual patients whenever available. Outcome frequencies were calculated only among patients for whom the relevant feature was reported. Results: The patient developed infantile spasms at 5 months of age after an initially unremarkable brain MRI and subsequently showed drug-resistant epilepsy, profound developmental impairment, progressive microcephaly, spastic tetraparesis, feeding difficulties, and severe cortical and subcortical atrophy. Exome sequencing identified compound-heterozygous ASNS variants: the novel early frameshift variant c.81_82del (p.Gly28SerfsTer7) and the previously reported c.97C>T (p.Arg33Cys), confirmed in trans. The systematic review included 106 published molecularly confirmed patients. Developmental impairment was reported in 101/101 assessable patients, microcephaly in 99/106, epilepsy in 72/86, and at least 48 deaths were documented. Exact individual CSF asparagine concentrations were available for only six patients; five were reduced or undetectable and one was within the local reference interval. Conclusions: The novel c.81_82del variant expands the molecular spectrum of ASNSD. The available evidence does not permit calculation of a validated diagnostic threshold, sensitivity, specificity, or predictive values for CSF asparagine. A reduced concentration may support the diagnosis, whereas a normal concentration does not exclude ASNSD. Molecular testing remains the diagnostic standard and should be considered early in patients with developmental and epileptic encephalopathy, progressive microcephaly, and cerebral atrophy, even when early MRI or routine metabolic investigations are unrevealing.

Yazarların özeti; kaynağından alınmıştır. Biomolecules, 2026 · DOI ↗