AN ALTERNATIVE CAUSE OF A LEIGH-LIKE PHENOTYPE: VAC14-RELATED DISEASE
SSIEM 2026 ANNUAL SYMPOSIUM: NEXT GENERATİON METABOLİC MEDICINE, Helsinki, Finlandiya, 25 - 28 Ağustos 2026, ss.154, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Helsinki
- Basıldığı Ülke: Finlandiya
- Sayfa Sayıları: ss.154
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
Introduction The VAC14 gene encodes a protein that regulates the PIKfyve complex, which is involved in endosomal–lysosomal membrane trafficking. VAC14-related disorders represent a rare cause of childhood-onset progressive neurodegeneration with basal ganglia involvement. The clinical presentation typically includes developmental regression, hypotonia, and movement disorders; it may also manifest as a Leigh-like phenotype in the early stages. In this report, we present a case of severe infantile-onset neurodegeneration with a homozygous VAC14 variant. A 15-month-old girl with a suspected diagnosis of Leigh syndrome was referred to our clinic due to hypotonia, developmental regression, and bilateral basal ganglia involvement on brain MRI. Her prenatal, natal, and postnatal histories were unremarkable. Her parents are third-degree consanguineous. The patient was able to sit independently at 9 months but lost this ability at 11 months. Progressive hypotonia developed during this period. At 13 months, brain MRI demonstrated increased T2 signal intensity in the bilateral caudate and putamen, as well as signal changes in the posterior periventricular and frontal subcortical white matter. MR spectroscopy demonstrated a mild lactate peak. Plasma lactate and alanine levels, along with urinary organic acid analysis, were within normal limits, making Leigh syndrome less likely. The patient was treated with biotin, thiamine, riboflavin, alpha-lipoic acid, and coenzyme Q10; however, these interventions provided no clinical benefit and were subsequently discontinued. Whole-exome sequencing and mitochondrial genome analysis did not reveal any pathogenic variants that could explain the patient’s clinical phenotype. Whole-genome sequencing subsequently identified a homozygous p.Arg623Cys (NP_060522.3) variant in the VAC14 gene. Based on the clinical and radiological findings, the patient was diagnosed with VAC14-related neurodegenerative disease. Conclusion VAC14-related neurodegenerative disease was first described in 2016 by Lenk et al. in patients with early childhood-onset progressive neurological disease and basal ganglia degeneration. Reported cases in the literature remain very limited. This case further expands the clinical spectrum of VAC14-related neurodegenerative disorders.