{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:09:31Z","timestamp":1780542571029,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder. Biallelic pathogenic variants in\n                      <jats:italic>ABHD16A<\/jats:italic>\n                      have recently been linked to a neurodevelopmental phenotype featuring early-onset spasticity and global developmental delay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To further define the clinical and genetic spectrum of\n                      <jats:italic>ABHD16A<\/jats:italic>\n                      -associated disease through the characterization of a novel pediatric case and an updated literature review.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated a child presenting with global developmental delay and progressive spastic paraplegia. Whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. Clinical features were documented prospectively, and a systematic review of published cases was conducted to assess phenotypic patterns and genotype\u2013phenotype relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Consistent with prior reports, the core features of\n                      <jats:italic>ABHD16A<\/jats:italic>\n                      -related disease include global developmental delay, intellectual disability, and spastic paraplegia, often with early onset. In our patient, tandem mass spectrometry revealed elevated long-chain acylcarnitines (C16, C18:1, C18:2)\u2014a metabolic abnormality not previously described in this condition. WES identified two novel compound heterozygous frameshift variants in\n                      <jats:italic>ABHD16A<\/jats:italic>\n                      : c.119delA (p.His40Leufs49) and c.559_562del (p.Pro187Cysfs29), both confirmed by Sanger sequencing and classified as pathogenic (ACMG criteria: PVS1, PM2, PM3, PP1). Our literature review identified 17 additional individuals from 9 families, enabling a refined clinical delineation: most patients exhibited motor and speech delay, axial hypotonia evolving into spasticity, and variable degrees of cognitive impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      To our knowledge, this is the first reported case of\n                      <jats:italic>ABHD16A<\/jats:italic>\n                      -related neurodevelopmental disorder in a Chinese patient. We provide a detailed phenotypic characterization and an updated review of the published literature to support clinical recognition and genetic diagnosis of this emerging condition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2025.1724515","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:37:47Z","timestamp":1767595067000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Expansion of the genetic and phenotypic spectrum of hereditary spastic paraplegia caused by ABHD16A gene variants: an integrated analysis based on novel variants and literature 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