Primary coenzyme Q10 deficiency type 7 (CoQ10D7) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous mutation in the COQ4 gene on chromosome 9q34. The c.370G > A mutation in the COQ4 gene has been identified as a founder mutation in the Southern China. We established an induced pluripotent stem cell (iPSC) line from a patient harboring the c.370G > A homozygous mutation. The cell line exhibited typical iPSC morphology, expressed high levels of stemness markers, and exhibited normal karyotype. The generation of these iPSCs provides a valuable CoQ10D7 model for studying the molecular and cellular consequences of CoQ10 deficiency.

A patient with primary CoQ10 deficiency associated with the c.901 C > T (p.R301W) (rs140246430) homozygous missense pathogenic variant in the COQ8A gene, who presented with recurrent status epilepticus, stroke-like lesions, and hypertrophic cardiomyopathy while being followed-up with early-onset autosomal recessive cerebellar ataxia will be reported in this article. A 16-year-old patient who was being followed up at an external center with a diagnosis of ataxia with cerebellar atrophy had been seen 3 different times within a year for status epilepticus. The cerebral MRI showed severe cerebellar atrophy, stroke like lesions, and an inverted double- lactate peak on spectroscopy. Her echocardiography revealed marked left ventricular hypertrophy. Mitochondrial cocktail therapy containing a standard dose of CoQ10 was started, considering mitochondrial disease. The patient died due to cardiomyopathy. Mitochondrial panel analysis revealed the presence of the c.901 C > T (p.R301W) homozygous missense mutation in the COQ8A gene. Primary Coenzyme Q10 deficiency should be considered in patients presenting with autosomal recessive stable-appearing progressive ataxia, emerging attacks of status epilepticus, stroke-like lesions on neuroimaging, and cardiomyopathy. Since there is a case with the same mutation with a similar fatal course in the literature, detection of c.901 C > T (p.R301W) mutation homozygously should be a warning for a severe prognosis and more aggressive treatment should be started without delay with a high dose of CoQ10 instead of the lower doses used in the treatment of mitochondrial disease.

Primary coenzyme Q10 deficiency-1, caused by COQ2 disease-causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband-only whole-exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long-read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy.

Cerebellar ataxia is a neurological syndrome characterized by the imbalance (e.g., truncal ataxia, gait ataxia) and incoordination of limbs while executing a task (dysmetria), caused by the dysfunction of the cerebellum or its connections. It is frequently associated with other signs of cerebellar dysfunction, including abnormal eye movements, dysmetria, kinetic tremor, dysarthria, and/or dysphagia. Among the so-termed mitochondrial ataxias, variants in genes encoding steps of the coenzyme Q10 biosynthetic pathway represent a common cause of autosomal recessive primary coenzyme Q10 deficiencies (PCoQD)s. PCoQD is a potentially treatable condition; therefore, a correct and timely diagnosis is essential. After a brief presentation of the illustrative case of an Italian woman with this condition (due to a novel homozygous nonsense mutation in COQ8A), this article will review ataxias due to PCoQD.

Coenzyme Q10 deficiency can be due to mutations in Coenzyme Q10-biosynthesis genes (primary) or genes unrelated to biosynthesis (secondary). Primary Coenzyme Q10 deficiency-4 (COQ10D4), also known as autosomal recessive spinocerebellar ataxia-9 (SCAR9), is an autosomal recessive disorder caused by mutations in the ADCK3 gene. This disorder is characterized by several clinical manifestations such as severe infantile multisystemic illness, encephalomyopathy, isolated myopathy, cerebellar ataxia, or nephrotic syndrome. In this study, whole-exome sequencing was performed in order to identify disease-causing variants in an affected girl with developmental regression and Epilepsia Partialis Continua (EPC). Next, Sanger sequencing method was used to confirm the identified variant in the patient and segregation analysis in her parents. The proband is an affected 11-year-old girl with persistent seizures, EPC, and developmental regression including motor, cognition, and speech. Seizures were not controlled with various anticonvulsant drugs despite adequate dosing. Progressive cerebellar atrophy, stroke-like cortical involvement, multifocal hyperintense bright objects, and restriction in diffusion-weighted imaging (DWI) were seen in the brain magnetic resonance imaging (MRI). A novel homozygous missense variant [NM_020247.5: c.814G>T; (p.Gly272Cys)] was identified within the ADCK3 gene, which is the first mutation in this gene in the Iranian population. Bioinformatics analysis showed this variant is damaging. Based on our patient, clinicians should consider genetic testing earlier to instant diagnosis and satisfactory treatment based on exact etiology to prevent further neurologic sequelae.