Reyes Syndrome

Fatty Acid Oxidation Defects

Alyssa Williams

What is Reyes Syndrome

characterized by non-ketoic hypoglycemia, hyperammonemia, encephalopathy, lethargy, accumulation of fatty acids in liver originally a condition brought on by aspirin used to treat viral illness then discovered it was more commonly due to IEM seen in prolonged fasting & FAOD

Fatty Acid Oxidation Defects

Inborn Error of Metabolism (IEM) mostly autosomal recessive mutation usually causing deficiency of acyl CoA dehydrogenases for beta oxidation most common form is deficiency of Medium Chain Acyl CoA Dehydrogenase ( MCAD deficiency)

Fatty Acid Oxidation Defects

MCAD defects: ACADM gene chromosome 1 (1p31) commonly lysine is replaced with glutamic acid (position 304)

http://www.genecards.org/pics/loc/ACADM-gene.png

Fatty Acid Oxidation Defects

VLCAD defects: ACADVL gene chromosome 17 (17p13.1) usually missense, premature stop codon causes most severe cases

http://ghr.nlm.nih.gov/dynamicImages/chromomap/ACADVL.jpeg

Fatty Acid Oxidation Defects

LCAD defects: ACADL gene chromosome 2 (2q34-q35)

http://ghr.nlm.nih.gov/dynamicImages/chromomap/ACADL.jpeg

Fatty Acid Oxidation Defects

SCAD defects: ACADS gene chromosome 12 (12q.24.31) majority of mutations are missense mutations

http://ghr.nlm.nih.gov/dynamicImages/chromomap/ACADS.jpeg

Deficiency of Enzyme in Beta Oxidation

http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14897250/dapoian_v2_1_2.j pg

Fatty acids build up in mitochondria without undergoing complete beta oxidation into energy

Deficiency of Enzyme in Beta Oxidation

http://www.google.com/imgres?q=mitochondria&um=1&hl=en&rlz=1T4ADFA_enUS460US462&biw=1366&bih=533&tbm=isch &tbnid=ojdbd49kA9J09M:&imgrefurl=http://shs.westport.k12.ct.us/asr/Bio%25202/webquests/cell%2520city/organelle%2520links/ mitochondria.htm&docid=qUEPrBJGujAPmM&imgurl=http://shs.westport.k12.ct.us/asr/Bio%2525202/webquests/cell%252520city /organelle%252520links/mitochondria.gif&w=386&h=375&ei=jvyNTfiNMjv0gHc1qC5Dw&zoom=1&iact=rc&dur=49&sig=103012142681632561373&page=1&tbnh=147&tbnw=151&start=0&ndsp= 12&ved=1t:429,r:19,s:0,i:122&tx=92&ty=59

Symptoms
Non-Ketoic Hypoglycemia The products from Beta Oxidation are used in ketogenesis Without complete oxidation, there are no resources to make ketones

Lethargy ketones are used to fuel brain and muscles during fasting

http://www.geraldinemorgan.cl/Articles/English/Fatty_Acid_Oxidation/ketonesynthesis.jpg

Hyperammonemia Research suggests increased fatty acids in the liver may play a role in shutting down the urea cycle, preventing excretion of ammonia
Encephalopathy Due to toxicity in the brain caused by the hyperammonemia

Symptoms

http://www.blackwellpublishing.com/korfgenetics/jpg/300_96dpi/Fig11-7.jpg

Treatment & Screening

Newborn screening tests for IEM Once diagnosed avoid fasting, high carb/low fat diet Monitor blood glucose levels

http://www.mayoclinic.com/health/reyes-syndrome/DS00142/DSECTION=symptoms http://www.uthsc.edu/bcdd/services/programs/iem_pdf/Fatty_Acid_Disorders.pdf http://ghr.nlm.nih.gov/gene/ACADM http://ghr.nlm.nih.gov/gene/ACADVL http://ghr.nlm.nih.gov/gene/ACADS http://ghr.nlm.nih.gov/gene/ACADL http://wiki.medpedia.com/Reye's_Syndrome http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359173/ http://www.sciencedirect.com/science/article/pii/S0925443999000253 http://www.myspecialdiet.com/lcfao.aspx http://kidshealth.org/parent/system/medical/newborn_screening_tests.html http://emedicine.medscape.com/article/803683-overview http://www.idph.state.il.us/HealthWellness/fs/mcad.htm http://preventiongenetics.com/ClinicalTesting/testdescriptions/acadvl.pdf http://wiki.medpedia.com/Acyl-Coenzyme_A_dehydrogenase,_C-2_to_C3_short_chain_(ACADS)