Classical pyridoxine-sensitive homocystinuria in siblings: clinical and genetic features and approaches to individualized treatment. Case report

Classical homocystinuria (HCU), caused by cystathione-β-synthase deficiency, is a rare hereditary metabolic disorder with a high risk of systemic complications if not diagnosed and treated promptly. Extended neonatal and family screening are critical for early detection. This publication presents the clinical and genetic characteristics, as well as therapeutic outcomes, in two siblings with classical pyridoxine-responsive HCU. Two clinical cases involving siblings with HCU are presented. Diagnostic procedures included extended neonatal screening, quantification of methionine and total homocysteine levels, and molecular genetic analysis of the CBS gene. The efficacy of dietary therapy, pyridoxine, metabolic cofactors, and betaine was assessed longitudinally. Both patients exhibited a previously unreported pathogenic CBS gene variant (c.430G>C, p.Glu144Gln) in the homozygous state. The younger sibling was diagnosed during the neonatal period, while the older sibling was identified through family cascade screening. Both patients demonstrated an excellent response to pyridoxine and achieved target homocysteine concentrations with individualized dietary therapy and metabolic support. No severe clinical complications occurred during the follow-up period. The presented clinical cases confirm the effectiveness of early diagnosis and a personalized approach to the treatment of classical HCU. The availability and development of specialized Russian medical nutrition products, including a methionine-free mixture for "Homocystinuria" and the amino acid module "Betaine" under the trade mark "ОРФАНИК®", are essential for sustained metabolic control. Incorporation of the Aromin Flavor Module into amino acid-based mixtures improves adherence to dietary therapy.