Table 2.

Primary UQ₁₀ deficiency in humans.

Gene	Mutations	Level of UQ10 (% of mean control value)	Biochemical dysfunction	Number of patients (families) Age of onset	Family History	Symptoms	Response to UQ10 therapy	References
PDSS1	hom, D308E	<5% (fibroblasts)	Decreased activities of CI+III and CII+III in either fibroblasts or muscle	2(1) 1–2 yr	Parents and 3 other children are healthy.	Encephaloneuropathy, deafness, cardiac valvulopathy, obesity, livedo reticularis	Yes, Active at 22 yr	(Mollet et al., 2007)
PDSS2	het, Q332X+S382L	14% (muscle) 13% (fibroblasts)	Decreased CII+III activity (muscle +fibroblasts), deficit in ATP synthesis (fibroblasts)	1(1) <3 mo	Parents are healthy heterozygous carriers with normal levels of UQ10. Patient has 1 sibling who is healthy.	Nephrotic syndrome, Leigh syndrome, ataxia, seizure	No died at age 8 mo (refractory status epilepticus)	(Quinzii et al., 2008, Lopez et al., 2006, Salviati et al., 2012)
COQ2	het, R197H+N228S	Severe (kidney + muscle) 36% (fibroblasts)	Decreased CII–III activity (kidney cortex + skeletal muscle), elevated citrate synthase activity (skeletal muscle), impaired cell growth, reduced ATP level, increased ROS (fibroblasts)	1(1) 18 mo	1 sibling who carries a N228S mutation and appears healthy	Steroid-resistant nephritic syndrome	yes	(Diomedi-Camassei et al., 2007, Quinzii et al., 2010)
	hom,S146N	Severe (kidney + muscle)	Decreased CII–III activity (kidney cortex + skeletal muscle), elevated citrate synthase activity (skeletal muscle)	1(1) Birth	1 healthy sibling, 1 dead sibling (at 2 d of life)	Acute renal failure, encephalomyopathy	No, died at age 6 mo	(Diomedi-Camassei et al., 2007)
	hom, Y297C	37% (muscle) 18–30% (fibroblasts)	Growth defect, decreased CII–III activity, deficit in ATP synthesis, impaired pyrimidine synthesis, increased ROS production (fibroblasts), decreased activities of CI+III and CII+III (muscle)	2(1) 11–12 mo	Parents are healthy heterozygous carriers	Male: naystagmus, encephalomyopathy, steroid-resistant NS (nephrotic syndrome), seizures, hepatopathy, cerebellar atrophy, tremor Famale: isolated NS at 12 mo of life	Yes	(Quinzii et al., 2006, Quinzii et al., 2008, Diomedi-Camassei et al., 2007)
	hom,N401fsX415	24% (fibroblasts)	Reduced complex I+III and II+III activities (liver)	2(1) Birth	Both parents are hererozyous for the single nuclear deletion	Infantile multiorgan failure	No died at age 1–12d	(Mollet et al., 2007, Quinzii and Hirano, 2010)
COQ4	Monoallelic deletion	44% (fibroblasts)	Decreased CII+III activity, reduced growth rate (fibroblasts)	1(1) 3 yr	No sibling, parents are healthy	Dysmorphic features, metal retardation, hypotonia, encephalomyopathy	Yes	(Salviati et al., 2012)
COQ6	hom, G255R	-	-	6(2) 0.2–6.2 yr	Parents are heterozygous carriers	SRNS (steroid-resistant nephrotic syndrome)	Yes	(Heeringa et al., 2011)
	hom, A353D	-	-	3(2) 2.5–6.0 yr	Parents are heterozygous carriers	SRNS (steroid-resistant nephrotic syndrome)	Yes	(Heeringa et al., 2011)
	het, W447X+Q461fsX478	-	-	1(1) 3.0 yr	Parents are heterozygous carriers	SRNS (steroid-resistant nephrotic syndrome)	-	(Heeringa et al., 2011)
	het, R162X +? *	-	-	-		Cyclosporine A-dependent nephritic syndrome	-	(Heeringa et al., 2011)
	het, W188X+?*	-	-	-		Diffuse mesangial sclerosis	-	(Heeringa et al., 2011)
ADCK3	het, R213W+G272V	29% (muscle)	High CIV/CII+III and CII+III/CII activity ratios (muscle), elevated individual enzyme activies (CI, CII, CIII, CIV), a slight increase of CIV/CII+III (fibroblasts)	2(1) 1 mo	Parents are healthy. Two old siblings are heterozygous carriers for the R213W mutation and they are healthy.	Hypotonia, development delay, talus valgus, seizures, cerebellar ataxia, epilepsia partialis continua	No	(Mollet et al., 2008)
	Hom, E551K	8% (mucle) 100% (fibroblasts)	Decreased oxygen consumption rate, reduced CII–III acivity (musle), a slight increase of CIV/CII+III (fibroblasts)	1(1) 18 mo	Parents are healthy heterozygous carriers. One old sister is healthy.	Cerebella ataxia, strabismus, muscle weakness, tonic seizure	No	(Mollet et al., 2008)
	het, G272D +1bp freameshit insertion c[1812_1813insG]	5% (mucle) 100% (fibroblasts)	Decreased CI–III and CII–III activities, elevated activities of individual complexes and citrtate synthase (muscle)	1(1) 3 yr	Parents are healthy. No siblings.	Exercise intolerance, cerebellar syndromes	Yes	(Mollet et al., 2008, Aure et al., 2004)
	hom, D420WfsX40, I467Afs X22	119% (fibroblasts)	Decreased CI–III activity, normal ATP levels, no ROS overproduction	4(1) 8 – 11 yr	One healthy sibling	Cerebellar ataxia, exercise intolerance	-	(Lagier-Tourenne et al., 2008, Quinzii et al., 2010)
	hom, Q167Lfsx36	64% (fibroblasts)	Decreased CI–III activity, normal ATP levels, no ROS overproduction	1(1) 4 yr	-	Cerebellar ataxia	-	(Lagier-Tourenne et al., 2008, Quinzii et al., 2010)
	het, Y514C+T584 del	51% (fibroblasts)	Decreased CI–III activity, normal ATP levels, no ROS overproduction	1(1) 5 yr	-	Cerebellar ataxia	Yes	(Lagier-Tourenne et al., 2008, Quinzii et al., 2010)
	het, K314_Q360 del+ G549S	-	-	1(1) 3 yr	-	Cerebellar ataxia	-	(Lagier-Tourenne et al., 2008)
COQ9	hom, R244X	15% (muscle) 18% (fibroblasts)	Low CII–III activity (muscle) markedly decreased ATP level, no signs of ROS overproduction (fibroblasts)	1(1) birth	Parents and other 5 siblings are healthy. An old sister died on day one of life.	Renal tubulopathy, ventricular hypertrophy, seizure, cerebellar atrophy, development delay	No Died at 2 yr	(Rahman et al., 2001, Quinzii et al., 2010, Quinzii and Hirano, 2010, Duncan et al., 2009)

hom: homozygous; het: heterozygous; mo: month; yr: year;

^*the second mutation has not been identified.