Jeannette C Bleeker1,2,3, Irene L Kok1,4, Sacha Ferdinandusse2, Maaike de Vries5, Terry G J Derks6, Margot F Mulder7, Monique Williams8, Estela Rubio Gozalbo9, Annet M Bosch3, Dorine T van den Hurk4, Monique G M de Sain-van der Velden10, Hans R Waterham2, Frits A Wijburg3, Gepke Visser1,3. 1. Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital (UMCU), University Medical Center Utrecht, Internal Mail KE 04.306.0, PO Box 85090 3508 AB, Utrecht, Netherlands. 2. Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, Netherlands. 3. Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 4. Department of Internal Medicine and Dermatology, Dietetics, University Medical Center Utrecht, Utrecht, Netherlands. 5. Department of Pediatrics, Radboud University Medical Center, Nijmegen, Netherlands. 6. Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, Netherlands. 7. Department of Pediatrics, VU University Medical Center Amsterdam, Amsterdam, Netherlands. 8. Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, Netherlands. 9. Department of Pediatrics and Laboratory Genetic Metabolic Diseases, Maastricht University Medical Center, Maastricht, Netherlands. 10. Department of Medical Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Abstract
BACKGROUND: Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments. OBJECTIVE: To define dietary strategies for individuals with VLCADD based on the predicted phenotype. METHOD: We evaluated long-term dietary histories of a cohort of individuals diagnosed with VLCADD identified before the introduction of VLCADD in NBS and their beta-oxidation (LC-FAO) flux score (rate of oleate oxidation) in cultured skin fibroblasts in relation to the clinical outcome. Based on these results a dietary strategy is proposed. RESULTS: Sixteen individuals with VLCADD were included. One had an LC-FAO flux score >90%, was not on a restricted diet and is asymptomatic to date. Four patients had an LC-FAO flux score <10%, and significant VLCADD related symptoms despite the use of strict diets including LCT restriction, MCT supplementation and nocturnal gastric drip feeding. Patients with an LC-FAO flux score between 10 and 90% (n = 11) showed a more heterogeneous phenotype. CONCLUSIONS: This study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC-FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC-FAO flux score.
BACKGROUND:Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acidoxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments. OBJECTIVE: To define dietary strategies for individuals with VLCADD based on the predicted phenotype. METHOD: We evaluated long-term dietary histories of a cohort of individuals diagnosed with VLCADD identified before the introduction of VLCADD in NBS and their beta-oxidation (LC-FAO) flux score (rate of oleate oxidation) in cultured skin fibroblasts in relation to the clinical outcome. Based on these results a dietary strategy is proposed. RESULTS: Sixteen individuals with VLCADD were included. One had an LC-FAO flux score >90%, was not on a restricted diet and is asymptomatic to date. Four patients had an LC-FAO flux score <10%, and significant VLCADD related symptoms despite the use of strict diets including LCT restriction, MCT supplementation and nocturnal gastric drip feeding. Patients with an LC-FAO flux score between 10 and 90% (n = 11) showed a more heterogeneous phenotype. CONCLUSIONS: This study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC-FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC-FAO flux score.
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