A novel mutation in COQ2 leading to fatal infantile multisystem disease.
Coenzyme Q10 (ubiquinone or CoQ10) serves as a redox carrier in the mitochondrial oxidative phosphorylation system. The reduced form of this lipid-soluble antioxidant (ubiquinol) is involved in other metabolic processes as well, such as preventing reactive oxygen species (ROS) induced damage from the mitochondrial membrane. Primary coenzyme Q10 deficiency is a rare, autosomal recessive disorder, often presenting with neurological and/or muscle involvement. Until now, five patients from four families have been described with primary coenzyme Q10 deficiency due to mutations in COQ2 encoding para-hydroxybenzoate polyprenyl transferase. Interestingly, four of these patients showed a distinctive renal involvement (focal segmental glomerular sclerosis, crescentic glomerulonephritis, nephrotic syndrome), which is only very rarely seen in correlation with mitochondrial disorders. The fifth patient deceases due to infantile multi organ failure, also with renal involvement. Here we report a novel homozygous mutation in COQ2 (c.905C>T, p.Ala302Val) in a dizygotic twin from consanguineous Turkish parents. The children were born prematurely and died at the age of five and six months, respectively, after an undulating disease course involving apneas, seizures, feeding problems and generalized edema, alternating with relative stable periods without the need of artificial ventilation. There was no evidence for renal involvement. We would like to raise awareness for this potentially treatable disorder which could be under diagnosed in patients with fatal neonatal or infantile multi-organ disease.
Laboratory of Clinical Chemistry and Hematology, St. Elisabeth Hospital, Tilburg, The Netherlands.
Bernadette S
BS
Jakobs
Lambert P
LP
van den Heuvel
Roel J P
RJ
Smeets
Maaike C
MC
de Vries
Steffen
S
Hien
Thomas
T
Schaible
Jan A M
JA
Smeitink
Ron A
RA
Wevers
Saskia B
SB
Wortmann
Richard J T
RJ
Rodenburg
D019883:Alkyl and Aryl Transferases / Q000172:deficiency* / Q000235:genetics*; D000595:Amino Acid Sequence; D004200:Diseases in Twins / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase