Table 1.
Clinical and biochemical characteristics of known patients with COQ7-associated primary CoQ10 deficiency
| Freyer et al, 2015 | Wang et al, 2017 | Kwong et al, 2019 | Hashemi et al, 2020 | Wang et al, 2022 |
Jacquier et al, 2022 (II-2) |
Jacquier et al, 2022 (II-1) |
Jacquier et al, 2022 (II-3) |
Sadr, et al, 2023 | Patient 1 |
Patient 2 |
Patient 3 |
Patient 4 |
Patient 5 |
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variant | c.422T>A p.(Val141Glu) | c.332T>C (p.Leu111Pro) c.308C>T (p.Thr103Met) | c.599_600 delinsTAATGCATC (p.Lys200Ilefs*56) c.319C>Tp. (Arg107Trp) | c.332T>C (p.Leu111Pro) c.308C>T (p.Thr103Met) | c.161G>A (p.Arg54Gln) | c.3G>T (p.Met1?) | c.3G>T (p.Met1?) | c.3G>T (p.Met1?) | c.332T>C (p.Leu111Pro) c.308C>T (p.Thr103Met) | c.161G>A (p.Arg54Gln) c.446A>G (p.Tyr149Cys) | c.446A>G (p.Tyr149Cys) c.3G>T (p.Met1?) | c.161G>A (p.Arg54Gln) | c.161G>A (p.Arg54Gln) | c.3G>T (p.Met1?) |
| Zygosity | Homozygous | Homozygous (both) | Compound heterozygous | Homozygous (both) | Homozygous | Homozygous | Homozygous | Homozygous | Homozygous | Compound heterozygous | Compound heterozygous | Homozygous | Homozygous | Homozygous |
| Gender | Male | Female | Male | Female | Male | Male | Female | Male | Male | Male | Female | Female | Female | Female |
| Consanguinity | + | + | − | + | + | − | − | − | + | − | − | + | − | + |
| Gestational age when born | Full term | 37 weeks | 33 weeks | 38 weeks | 39 weeks | N/A | N/A | N/A | N/A | Full term | N/A | 32 weeks | 39 weeks | 38 weeks |
| Prenatal complications | Oligohydramnios, fetal lung hypoplasia, IUGR | Gestational diabetes | IUGR, cardiomegaly, TR, oligohydramnios | − | − | N/A | N/A | N/A | N/A | Oligohydramnios | N/A | Preterm labor. | − | − |
| SGA | + | − | + | − | − | N/A | N/A | N/A | N/A | − | N/A | − | − | N/A |
| Age at onset of symptoms | Birth | 14 months | Birth | 2 years | 15 months | 12 years | 9 years | 10 years | 13 months | Birth | 12 years | 3 years | 3 years | 5 years |
| Age at last examination/evaluation | 9 years | 6 years | 12 months | 9 years | 4.5 years | 36 years | 25 years | 42 years | 7 years | 15 years | 45 years | 9 years | 9 years | 33 years |
| Developmentaldelay | Moderate | − | Profound | − | + | − | − | -- | − | Severe | − | Mild | − | Mild |
| Intellectual disabilities | N/A | − | N/A | − | N/A | N/A | N/A | N/A | − | + | − | + | −. | + |
| Learning difficulties | + | + (Inattention) | N/A | + (Inattention) | N/A | N/A | N/A | N/A | − | + | + | + | − | + |
| Abnormal tone (hypo/hypertonia/spasticity) | Hypotonia, contracture of LE | Spastic paraparesis, mild truncal hypotonia | Generalized hypotonia | Spasticity | Hypotonia, spasticity, contracture LE | LE stiffness | N/A | N/A | Spasticity | Hypotonia, contracture LE | − | LE Spasticity | Spastic paraparesis | LE spasticity |
| LE Weakness | + | + | + | + | + | + | + | + | + | + | + | + | + | + |
| LE Spasticity | + | + | + | + | + | + | + | N/A | + | + | − | + | + | + |
| Muscularatrophy | + | + | + | − | N/A | + | N/A | + | − | − | − | + | − | + |
| Abnormal gait | + | + | N/A | + | + | + | + | + | + | + | + | + | + | + |
| Speech delay | − | N/A | N/A | − | + | N/A | N/A | N/A | − | + | − | + | − | + |
| Ophthalmologic | Visual dysfunction | − | Ptosis, bilateral visual loss | − | N/A | Myopia | N/A | N/A | − | Mild myopia | − | − | − | Microsaccadic eye movements during ocular pursuit |
| Audiologic | Mixed HL | Low frequency SNHL | Profound hearing impairment | Mild SNHL | N/A | − | N/A | N/A | Mild | SNHL | − | − | − | − |
| Cardiovascular | Systemic hypertension and LVH | N/A | Severe hypertrophic cardiomyopathy, TR and pericardial effusion | − | N/A | − | N/A | N/A | − | Mild dilation of ascending aorta | − | − | ASD | Arrhythmia |
| Respiratory | Lung hypoplasia with persistent pulmonary Hypertension of newborn | − | Central hypoventilation | − | N/A | N/A | N/A | N/A | − | Lung hypoplasia | − | Respiratory insufficiency inneonatal period. | − | − |
| Renal | Renal dysfunction with small dysplastic kidneys with impaired cortical differentiation | − | Multiple renal cysts and diffusely increased echogenicity with accentuation of cortico-medullary differentiation. | − | N/A | N/A | N/A | N/A | − | − | − | − | − | − |
| Gastrointestinal | Feeding difficulties, FTT | − | Feeding difficulties, FTT | − | N/A | N/A | N/A | N/A | N/A | Feeding difficulties, FTT | − | − | − | − |
| Brain MRI | Normal | Normal | Subdural hematoma, basal ganglial and thalami hypodensities with abnormal lactate peak | Normal | Increased T2A and Flair signal in the supratentorial bilateral periventricular white matt er. | Normal | N/A | N/A | Normal | Left posterior temporal infarction. Elevated lactate peak. | Normal | Enlargement of lateral ventricles, mainly of post erior horns, with thinner of white matter adjacent to ventricles | Thinning of the corpus callosum | N/A |
| EMG | Peripheral sensor imotor polyneuropathy of axonal and demyelinating type | N/A | N/A | Normal | N/A | Pure motor axonal neuropathy affecting predominantly distal lower extremities. . | Pure motor axonal neuropathy affecting predominantly distal lower extremities. . | N/A | N/A | N/A | Motor neuropathy, primarily axonal process | Diffuse involvement of a second motor neuron or axonal motor neuropathy | Motor axonal neuropathy | Motor axonal impairment affecting the distal museulature of all extremities |
| Respiratory chain enzymes | Complex I + III and IV deficiency | N/A | Complex II + III deficiency with normal isolated activity of complex II and complex III | N/A | N/A | N/A | N/A | N/A | N/A | Normal | N/A | Decreased Complex II + III and IV activities | Normal | N/A |
| Biochemical findings | ||||||||||||||
| Blood (amino acids, carnitine/acylcarnitine profile, ie) | N/A | Normal | Elevated alanine | Normal | N/A | N/A | N/A | N/A | N/A | Normal | Increased long-chain acylcarnitine species (C12-C18) | Normal | Normal | N/A |
| Hyperlactatemia (mean value and range) | + | − | + | − | N/A | N/A | N/A | N/A | N/A | + | − | − | − | N/A |
| Urine (amino acids, organic acids, ie) | Moderately increased excretion of fumarate and malate | Normal | Increased lactate, pyruvate, 3-hydroxybutyrate, dicarboxylic aciduria and TCA cycle intermediates. | N/A | Normal | N/A | N/A | N/A | N/A | Increased quinolinic and oxalic acid in infancy. Repeat testing at 7 yo was normal | Increased 4-hydroxy phenylacetate | Normal | Normal | N/A |
| CSF (amino acids, lactate,ie) | Elevated CSF lactate and slightly increased albumin | Elevated CSF lactate, slight decrease in total protein | N/A | N/A | N/A | N/A | N/A | N/A | N/A | Elevated CSF lactate | N/A | N/A | Normal | N/A |
| Treatment | CoQ10 | CoQ10 11.4 mg/kg twice daily | CoQ10 20 mg/kg/d | CoQ10 | None | N/A | N/A | N/A | CoQ10 11.4 mg/kg/d | Ubiquinol 450 mg BID | CoQ10 800 mg/day | CoQ10 300 mg/d | None | N/A |
Abbreviation: ASD- atrial septal defect; CoQ10- Coenzyme Q10; CSF- cerebrospinal fluid; EMG- electromyography; FTT- failure to thrive; HL- hearing loss; IUGR- intrauterine growth retardation; LE- lower extremities; LVH- left ventricular hypertrophy; N/A- not available; SGA- small for gestational age; SNHL- sensorineural hearing loss; TCA- tricarboxylic acids; TR- tricuspid regurgitation. Shaded columns- patients with neonatal-onset presentation of COQ7-associated primary CoQ10 deficiency