title: Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.
abstract: 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.
authors: Department of Medical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal. mjs.jano@gmail.com.|Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal. mjs.jano@gmail.com.
authors: Maria João Nabais
authors: MJ
authors: Sá
authors: Centro de Genética Médica Doutor Jacinto de Magalhães, CHP EPE, Porto, Portugal.|Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal.|Center for Health Technology and Services Research (CINTESIS), Porto, Portugal.
authors: Júlio C
authors: JC
authors: Rocha
authors: Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.|Centro de Genética Médica Doutor Jacinto de Magalhães, CHP EPE, Porto, Portugal.
authors: Manuela F
authors: MF
authors: Almeida
authors: Department of Medical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.
authors: Carla
authors: C
authors: Carmona
authors: Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.|Metabolic Disorders Consultation/Department of Pediatrics, Hospital de Santo António/Centro Hospitalar do Porto, Porto, Portugal.
authors: Esmeralda
authors: E
authors: Martins
authors: Department of Ophthalmology, Hospital de Santo António/Centro Hospitalar do Porto, Porto, Portugal.
authors: Vasco
authors: V
authors: Miranda
authors: Department of ENT, Hospital de Santo António/Centro Hospitalar do Porto, Porto, Portugal.
authors: Miguel
authors: M
authors: Coutinho
authors: Unit of Biochemical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.
authors: Rita
authors: R
authors: Ferreira
authors: Unit of Biochemical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.
authors: Sara
authors: S
authors: Pacheco
authors: Unit of Biochemical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.
authors: Francisco
authors: F
authors: Laranjeira
authors: Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.|Unit of Biochemical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.
authors: Isaura
authors: I
authors: Ribeiro
authors: Department of Medical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.
authors: Ana Maria
authors: AM
authors: Fortuna
authors: Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.|Unit of Biochemical Genetics, Centro de Genética Médica Dr. Jacinto de Magalhães/Centro Hospitalar do Porto, Porto, Portugal.
authors: Lúcia
authors: L
authors: Lacerda
keywords: Dietary treatment; Infantile Refsum disease; Peroxisomal biogenesis disorder; Phytanic acid; Psychomotor development; Very long chain fatty acids