JIMD Reports, Volume 26

Maria João Nabais Sá, Júlio C. Rocha, Manuela F. Almeida, Carla Carmona, Esmeralda Martins, Vasco Miranda, Miguel Coutinho, Rita Ferreira, Sara Pacheco, Francisco Laranjeira, Isaura Ribeiro, Ana Maria Fortuna, Lúcia Lacerda, Sá, Maria João Nabais, Rocha, Júlio C., Almeida, Manuela F., Carmona, Carla, Martins, Esmeralda, Miranda, Vasco, Coutinho, Miguel, Ferreira, Rita, Pacheco, Sara, Laranjeira, Francisco, Ribeiro, Isaura, Fortuna, Ana Maria, Lacerda, Lúcia

Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The authors report a 3-year-old child, born from consanguineous parents, who presented with developmental delay, retinitis pigmentosa, sensorineural deafness and craniofacial dysmorphisms. While the relative level of plasma C26:0 was slightly increased, other VLCFA were normal. Thus, a detailed characterization of the phenotype was essential to point to a ZSD. Repeatedly increased levels of plasma VLCFA, along with phytanic acid and pristanic acid, deficient dihydroxyacetone phosphate acyltransferase activity in fibroblasts and identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was proposed aiming phytanic acid dietary intake reduction. During dietary treatment, plasma levels of phytanic acid decreased to normal, and the patient's development evaluation showed slow progressive acquisition of new competences.This case report highlights the relevance of considering a ZSD in any child with developmental delay who manifests hearing and visual impairment and of performing a systematic biochemical investigation, when plasma VLCFA are mildly increased. During dietary intervention, a biochemical improvement was observed, and the long-term clinical effect of this approach needs to be evaluated.