Table 1.

Coq10 biosynthesis pathway genes mutated in human SRNS

Gene	Protein	Kidney phenotype	Extrarenal phenotype	CoQ10 dose	Outcome of CoQ10 treatment	References
PDSS1	Prenyldiphosphate synthase subunit 1	NS, tubular epithelial damage	Failure to thrive, developmental delay	−	−	[46]
PDSS2	Prenyldiphosphate	SRNS	Leigh syndrome	50 mg/day	No remission	[15]
	synthase subunit 2	SRNS		−	−	47]
		DMS	Encephalomyopathy, deafness, retinitis pigmentosa, hypertrophic cardiomyopathy	20 mg/kd/day		48]
COQ2	Coenzyme Q2 4-hydroxybenzoate polyprenyltransferase	FSGS	Encephalomyopathy, nystagmus secondary to bilateral optic nerve atrophy, seizures, and developmental delay, right hemiplegia, myoclonus, swallowing difficulties	30 mg/kg/day	1 patient partial remission, 1 patient kidney failure	[45, 49]
		NS	Seizures, liver failure, anemia, pancytopenia,insulin-dependent diabetes	−	−	[50]
		FSGS, crescentic glomerulonephritis	Epileptic encephalomyopathy, hypotonia, psychomotor delay, optic nerve atrophy,	30 mg/kg/day	No remission (kidney failure)	[16]
		FSGS		−	−	[51]
COQ6	Coenzyme Q6 monooxygenase	FSGS	Mild neurological symptoms	Unspecified	2 patients no remission (kidney failure)	[52]
		FSGS		30 mg/kg/day	1 patient remission, 1 patient partial remission, 1 patient kidney failure	[53]
		FSGS	Neonatal diabetes, seizures, hypotonia, encephalopathy, respiratory failure, cortical and subcortical stroke-like lesions in the frontal, insular, and temporal regions with diffuse cerebral atrophy	30 or 60 mg/kg/day		[54]
		FSGS, DMS	SND, ataxia, seizures, facial dysmorphism, growth retardation, nephrolithiasis, white matter abnormalities	15 or 30 mg/kg/day	Partial remission	[17]
		FSGS	Tetralogy of Fallot	Unspecified	Remission	[55]
		cFSGS	SND, mild muscle weakness in lower extremities, bilateral optic nerve atrophy, exotropia with nystagmus	−	−	[56]
		MPGN	None	Unspecified	Kidney failure	[52]
		FSGS, MCNS	None	30 mg/kg/day	Remission	[57]
		FSGS	SND	20 mg/kg/day	Initiated after kidney transplant to prevent neurological damage	[58]
		FSGS	SND, neurological impairment, optic atrophy	Idebenone 10 or 20 mg/kg/day	Enalapril treatment required for remission	[59]
COQ8B (ADCK4)	Coenzyme Q8B	FSGS, GS, cFSGS	Goiter, neurologic developmental delay, dilated cardiomyopathy, hypertension	−	−	[18]
		cFSGS, GTL	Neurologic abnormalities, seizures, mild mental retardation, retinitis pigmentosa	10 or 30 mg/kg/day	Partial remission	[21]
		FSGS, mesangial proliferative glomerulonephritis		−	−	[60]
		FSGS	Developmental delay	15 or 30 mg/kg/day	1 patient remission, 1 patient no remission	[61]
		FSGS	Dysplastic ears, moderate hearing loss	−	−	[62]
		FSGS	Seizure, pericardial effusion, hypertrophic cardiomyopathy, short stature, intellectual impairment, autism, hypothyroidism, pulmonary hypertension	20 or 30 mg/kg/day	Partial remission	[19]
		FSGS		150 mg/kg/day	Partial remission	[63]
		cFSGS, NOS	Medullary nephrocalcinosis, atrial septal defects, benign breast tumor, pancreatic pseudopapillary neoplasm	Cyclosporine	Remission	[64]

FSGS, focal segmental glomerulosclerosis; cFSGS, collapsing focal segmental glomerulosclerosis; GS, global glomerulosclerosis; GTL, FSGS tip lesion variant; idebenone, hydrophilic short-chain coenzyme Q 10 analog; NS, nephrotic syndrome, DMS, diffuse mesangial sclerosis; MCNS, minimal change nephrotic syndrome; MPGN, membranoproliferative glomerulonephritis; NOS, not-otherwise-specified variant of FSGS; SND, sensorineural deafness; SRNS, steroid-resistant nephrotic syndrome; remission—no proteinuria at study endpoint; partial remission—proteinuria improved but remained above normal range based on study cut off; no remission—no improvement in proteinuria