Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.
Adult Refsum disease (ARD) is associated with defective alpha-oxidation of phytanic acid (PA). omega-Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, omega-oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the omega-oxidation pathway was 6.9 (2.8-19.4) mg [20.4 (8.3-57.4) micromol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. omega-Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 +/- 58% in parallel with the 158 (125-603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The omega-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration. omega-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.
Wierzbicki
Anthony S
AS
Department of Chemical Pathology, Chelsea & Westminster Hospital, 369 Fulham Road, London, United Kingdom. anthony.wierzbicki@kcl.ac.uk
Mayne
Phillip D
PD
Lloyd
Matthew D
MD
Burston
David
D
Mei
Guam
G
Sidey
Margaret C
MC
Feher
Michael D
MD
Gibberd
F Brian
FB
D000272:Adipates / Q000652:urine*; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D003241:Consanguinity; D004032:Diet; D005215:Fasting; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010831:Phytanic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D012035:Refsum Disease / Q000097:blood / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism*
D000272:Adipates; D015415:Biomarkers; D010831:Phytanic Acid; C033274:3-methyladipic acid