Case of complex II with secondary fatty acid oxidation impairment

[Guest guest]

, You might be interested in this case history pasted below--

two patients with a primary complex II defect that resulted in a

secondary interference with fat metabolism. Interesting to note that

giving these patients EFAs (essential fatty acids) triggered

symptoms.

Take care,

Barbara

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J Inherit Metab Dis. 2003;26(7):659-70.

Respiratory complex II defect in siblings associated with a

symptomatic secondary block in fatty acid oxidation.

Gargus JJ, Boyle K, Bocian M, Roe DS, Vianey-Saban C, Roe CR.

Department of Physiology and Biophysics, University of California,

Irvine, Irvine, CA 92697-4034, USA. jjgargus@...

The mitochondrial oxidative phosphorylation and fatty acid oxidation

pathways have traditionally been considered independent major

sources of cellular energy production; however, case reports of

patients with specific enzymatic defects in either pathway have

suggested the potential for a complex interference between the two.

This study documents a new site of interference between the two

pathways, a site in respiratory complex II capable of producing

clinical signs of a block in fatty acid oxidation and reduced in

vitro activity of acyl-CoA dehydrogenases. The initial patient, and

later her newborn sibling, had mildly dysmorphic features, lactic

acidosis and a defect in mitochondrial respiratory complex II

associated with many biochemical features of a block in fatty acid

oxidation. Results of in vitro probing of intact fibroblasts from

both patients with methyl[2H3]palmitate and L-carnitine revealed

greatly increased [2H3]butyrylcarnitine; however, the ratio of

dehydrogenase activity with butyryl-CoA with anti-MCAD inactivating

antibody (used to reveal SCAD-specific activity) to that with

octanoyl-CoA was normal, excluding a selective SCAD or MCAD

deficiency. Respiratory complex II was defective in both patients,

with an absent thenoyltrifluoroacetone-sensitive succinate Q

reductase activity that was partially restored by supplementation

with duroquinone. Although secondary, the block in fatty acid

oxidation was a major management problem since attempts to provide

essential fatty acids precipitated acidotic decompensations. This

study reinforces the need to pursue broadly the primary genetic

defect within these two pathways, making full use of increasingly

available functional and molecular diagnostic tools.