Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy

Abstract

Introduction 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. Methods 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. Case PresentationThe 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). Conclusions 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.

COQ8A-Ataxia as a Manifestation of Primary Coenzyme Q Deficiency

“…In younger children, a developmental delay may occur as a first symptom. A common feature of mitochondrial diseases like COQ8A -ataxia is regression of development in patients who previously achieved milestones at the proper age [ 14 ]. Adolescents and older patients may require psychiatric care to treat distinctive disorders (depression, anxiety, psychotic disorder, or behavioral disturbances) in this particular group of patients [ 2 , 18 ].…”

“…Generalized tonic-clonic seizures are the most often reported. The wide range of seizure disorders includes well-controlled to multidrug-resistant epilepsy and even cases of epilepsia partialis continua and status epilepticus [ 12 , 14 ].The clinical presentation, also characteristic of juvenile age, is myopathic disorder, typically presented as muscle weakness or exercise intolerance [ 14 , 33 ]. In the group of less frequently reported neurological symptoms, pyramidal signs, disturbances in vibration sense, and swallowing difficulties have been described [ 11 , 27 , 32 ].…”

“…Even though CSF lactate concentration is found to be a more specific parameter, especially when the pathological process involves CNS, it may present within the normal range in COQ10D4 patients [ 32 , 42 ]. Moreover, metabolic evaluation, including urine organic acid profile, and concentration of serum amino acids are unremarkable in most cases [ 11 , 14 , 18 , 35 ]. In some patients, an increased level of phosphocreatine kinase (CK), creatine kinase-myocardial isoenzyme (CK-MB), lactate dehydrogenase (LDH), or liver parameters has been described [ 34 , 35 ].…”

“…Moreover, exacerbation of myoclonus after idebenone intake was reported [ 32 ]. As in other mitochondrial disorders, the use of sodium valproate should be avoided [ 14 ].…”

“…Cerebellar ataxia is the most common feature of this condition [ 4 ]. The prevalence of COQ8A -ataxia is unknown; so far, 123 patients from 24 different countries have been described [ 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. In this group, only one patient from Poland has been reported [ 31 ].…”