Docosahexaenoic acid therapy in peroxisomal diseases

Single-center randomized controlled trial at Johns Hopkins Hospital in Baltimore, Maryland, enrolling children with peroxisome assembly disorders, including Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. In the DHA arm, 25 participants were randomized in a 1:1 allocation design; participants were aged 1 month to 10 years and were advised to follow a low-phytanic diet.

Children in the active arm received oral docosahexaenoic acid (DHA) triglyceride 100 mg/kg/day plus arachidonic acid (AA) triglyceride 100 mg/kg/day, given daily for 1 year and mixed with food or infant formula. The comparator was placebo soybean oil.

DHA supplementation increased blood DHA levels but did not improve visual function, growth, or peroxisomal biochemical abnormalities. ERG outcomes showed no between-group difference (p = 0.813), and treatment effects were not significant for weight Z score (p = 0.824), height Z score (p = 0.147), C26:0 (p = 0.452), or plasmalogens (p = 0.981). The only clear biochemical change was a large rise in DHA levels in the treated group, from 5.31 (7.7) to 26.31 (20.8), versus 4.29 (6.4) to 6.74 (9.6) in placebo (p < 0.0001). Overall, the trial found no clinically meaningful benefit and concluded that DHA therapy cannot be endorsed for these disorders.

Small, rare-disease trial with limited sample size and incomplete per-arm analyzed counts reported. The cohort was heterogeneous across multiple peroxisome assembly disorders, and several outcomes had missing data, especially ERG assessments. Single-center design and 1-year follow-up limit generalizability and the ability to detect longer-term clinical effects.