Fumarase Deficiency: A Safe and Potentially Disease Modifying Effect of High Fat/Low Carbohydrate Diet

B Ryder; F Moore; A Mitchell; S Thompson; J Christodoulou; S Balasubramaniam

doi:10.1007/8904_2017_65

Fumarase Deficiency: A Safe and Potentially Disease Modifying Effect of High Fat/Low Carbohydrate Diet

JIMD Rep. 2018:40:77-83. doi: 10.1007/8904_2017_65. Epub 2017 Oct 21.

Authors

B Ryder¹, F Moore², A Mitchell³, S Thompson^{1

3}, J Christodoulou^{1

4

5

6

7}, S Balasubramaniam^{8

9

10}

Affiliations

¹ Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, NSW, Australia.
² NSW Biochemical Genetics Service, The Children's Hospital at Westmead, Sydney, NSW, Australia.
³ Metabolic Dietetic Service, The Children's Hospital at Westmead, Sydney, NSW, Australia.
⁴ Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁵ Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁶ Neurodevelopmental Genomics Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
⁷ Department of Paediatrics, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
⁸ Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, NSW, Australia. saras329@hotmail.com.
⁹ Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. saras329@hotmail.com.
¹⁰ Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. saras329@hotmail.com.

Abstract

Fumarate hydratase deficiency (FHD) caused by biallelic alterations of the FH (fumarate hydratase) gene is a rare disorder of the tricarboxylic acid cycle, classically characterized by encephalopathy, profound psychomotor retardation, seizures, a spectrum of brain abnormalities and early death in childhood. Less common milder phenotypes with moderate cognitive impairment and long-term survival have been reported. In addition, heterozygous mutations of the FH gene are responsible for hereditary leiomyomatosis and renal cell cancer (HLRCC). There is currently no recommended disease modifying treatment for FHD and only isolated reports of unsuccessful dietary modifications. Herein, we describe the safe and possibly disease modifying effect of a high fat, low carbohydrate diet in a 14-year-old female with severe FHD.

Keywords: Disease modifying; Fumarase deficiency; High fat diet.