Progressive Leukoencephalopathy Research Articles

A Novel <i>NDUFV2</i> Variant in an Asymptomatic Adolescent Girl with Progressive Cavitating Leukoencephalopathy

<b><i>Introduction:</i></b> Pathogenic variants in several genes encoding components of the mitochondrial respiratory chain have been linked to various clinical phenotypes such as progressive cavitating leukoencephalopathy (PCL). The association between PCL, previously linked to numerous gene mutations in the literature, and the <i>NDUFV2</i> gene mutations has emerged as a recent and noteworthy discovery. PCL is generally diagnosed in symptomatic patients during the early years of life, mostly in infancy. <b><i>Case Presentation:</i></b> In a previously healthy 12-year-old Turkish girl, a computed tomography scan taken for minor head trauma incidentally revealed suspicious hypodense areas in the periventricular white matter. Subsequently, a magnetic resonance imaging evaluation was performed. There was no history of motor regression, irritability, or seizures up to the age of 12. The case exhibited normal neurological and cranial nerve examinations. Magnetic resonance imaging detected bilateral periventricular T2/FLAIR hyperintensities with cystic areas suggestive of PCL. Whole-exome sequencing revealed the presence of a homozygous p.R222C missense variant in the <i>NDUFV2</i> gene. Over a 6-year follow-up period, the patient remained asymptomatic, and there were no discernible changes in the magnetic resonance imaging findings. <b><i>Conclusion:</i></b> This case underscores the association between a potentially causal variant at the <i>NDUFV2</i> locus and PCL. It is worth noting that this novel variation in PCL can not only manifest with symptoms in the infantile period but also remain asymptomatic into adolescence.

Delayed Progressive Leukoencephalopathy and Rash in a Patient with Cocaine Use (P6-4.010)

Delayed Progressive Leukoencephalopathy and Rash in a Patient with Cocaine Use (P6-4.010)

Possibilities of complex pharmacology protection of neurons and vessels of the brain in conditions of polymorbidity

Cerebrovascular pathology is currently one of the leading medical and social problems of our time, and the vast majority of vascular diseases of the brain belong to chronic disorders of cerebral blood circulation – cerebral atherosclerosis, stratification and aneurysms of cerebral arteries, progressive vascular leukoencephalopathy, hypertensive encephalopathy, non-purulent thrombosis of cerebral veins or venous sinuses, etc. The main link in the pathogenesis of these diseases is chronic ischemia of the brain. The prerequisite for safe pharmacotherapy of these conditions is the use of drugs containing biologically active substances of natural origin. It is advisable to use combined medicines as much as possible, which significantly reduces the main risks of polypharmacy, simplifies therapy regimens, increases compliance and significantly increases the economic availability of treatment. Combined means are the most successful and convenient. The modern pharmaceutical market of Ukraine offers a fairly small number of combined medicines, among which Vazavital Neuro and Graciven deserve special attention, the combined use of which is the most appropriate

DIVERSE NEUROLOGICAL MANIFESTATION OF HYPERIMMUNOGLOBULIN-E SYNDROME: A CASE SERIES

Hyper-immunoglobulin E (IgE) is a disorder of immune system characterized by assemblage of symptoms including recurrent skin and pulmonary infections, skeletal anomalies and elevated serum IgE (>2000 IU/ml). More recently, apart from the typical features, neurological manifestations have also been described including central nervous system infections, facial nerve palsy and demyelinating disorders. Here we describe three patients with hyper IgE syndrome having diverse neurological manifestation varying from CNS infection to basal ganglia stroke and progressive leukoencephalopathy.

A 33-year-old male patient with progressive leukoencephalopathy, early childhood cataract and recurrent diarrhea

A 33-year-old male patient with progressive leukoencephalopathy, early childhood cataract and recurrent diarrhea

AARS2-related Leukodystrophy Without Ovarian Failure Mimicking Multiple Sclerosis in a Female: A Case Report With a Novel Pathogenic Variant (P4-12.010)

<h3>Objective:</h3> N/A <h3>Background:</h3> <i>AARS2</i> mutations affect mitochondrial alanyl-transfer RNA (tRNA) synthetase. This enzyme is responsible of charging alanine to its cognate tRNA for protein translation within mitochondria. Individuals with <i>AARS2</i> mutations were reported to present either severe infantile cardiomyopathy or progressive leukoencephalopathy as the main clinical presentation. <i>AARS2</i>-related leukoencephalopathy is an ultra-rare white matter disorder, characterized by spasticity, ataxia, and impaired cognition. Further disease progression manifests as psychiatric illness and executive dysfunction. Ovarian failure is reported in almost all females with <i>AARS2</i>-related leukoencephalopathy. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 32-year-old female was referred to the clinic due to the development of progressive neurological symptoms since 2011. Ascending numbness of the lower limbs was the first clinical symptom that further extended to her abdomen. Patient, then, developed visual impairment in both eyes. Other symptoms included cognitive decline and language impairment that began abruptly with fast progression. She has one child and her menstrual cycles have been always regular. Multiple sclerosis was initially diagnosed and she was treated with corticosteroid, natalizumab, and rituximab without achieving improvements. The brain magnetic resonance imaging (MRI) of a patient performed in our institute showed multiple focal and confluent areas of diffusion restriction in bilateral periventricular and deep white matter, involving bilateral centrum semiovale/ corona radiate. Diffuse brain volume loss and bilateral thinning of optic nerves were observed. The MRI of thoracic spinal cord showed non-enhancing short segment T2 hyperintense lesions within the right ventral cord at T8-T9 and T12-L1. Molecular study reported a novel homozygous variant of c.929G&gt;T (p.Gly310Val) in <i>AARS2</i>. <h3>Conclusions:</h3> <i>AARS2</i>-related leukoencephalopathy in females can present without ovarian failure. The overlapping clinical and imaging features of white matter disorders may lead to misdiagnosis of the disease. Detailed review of clinical characteristics, MRI patterns, and molecular study can be helpful to reach to an accurate diagnosis. <b>Disclosure:</b> Mr. Amanat has nothing to disclose. Julie Cohen, 377 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Julie Cohen, 377 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Illumina. The institution of Julie Cohen, 377 has received research support from A Cure for Ellie. Dr. Fatemi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bluebirdbio. Dr. Fatemi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for RCO law. The institution of Dr. Fatemi has received research support from Minoryx. The institution of Dr. Fatemi has received research support from Viking Therapeutics. The institution of Dr. Fatemi has received research support from Swanbio Therapeutics . The institution of Dr. Fatemi has received research support from Autobahn Therapeutics. The institution of Dr. Fatemi has received research support from Nuvelution. The institution of Dr. Fatemi has received research support from NIH. The institution of Dr. Fatemi has received research support from A Cure for Ellie Foundation. The institution of Dr. Fatemi has received research support from Brian’s Hope Foundation . Dr. Fatemi has received intellectual property interests from a discovery or technology relating to health care. Dr. Fatemi has a non-compensated relationship as a Director (Board member) with ALDConnect that is relevant to AAN interests or activities. The institution of Dr. Fine has received research support from NIH.

Clues on Optical Coherence Tomography Leading to Diagnosis of Primary CNS Lymphoma (P2-9.012)

<h3>Objective:</h3> NA <h3>Background:</h3> Vitreoretinal lymphoma is a rare variant of primary central nervous system lymphoma (PCNSL). Around 20% of the PCNSL patients develop concurrent ocular involvement in the retina, vitreous, or optic nerve head. However, only 50% of these patients report visual symptoms, thus making a detailed ophthalmic examination a necessity. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 65-year-old man with history of hypertension and hyperlipidemia, presented with progressive hypersomnia, confusion, intermittent horizontal binocular diplopia, tremors, and blood pressure fluctuations over a course of 9 months. A magnetic resonance imaging of the brain with and without gadolinium contrast showed multifocal confluent cerebral and cerebellar enhancing and non-enhancing white matter abnormalities. Lumbar puncture revealed borderline pleocytosis (WBC 5) with negative cytology. The patient was referred to neuro-ophthalmology to be evaluated for ocular signs that may help with the diagnosis. At that visit, he was noted to have severe vision loss (visual acuity of 7/200) in the left eye that was not noticed by the patient until the time of examination. There was a left relative afferent pupillary defect. Further exam was notable for vitreous cells and yellow retinal placoid deposits. The optic nerve was normal. Optical coherence tomography (OCT) revealed multiple, hyper-reflective foci in the outer layers of the left macula with patchy discontinuity in the ellipsoid and photoreceptor layers. A vitreous biopsy detected CD20+, MYD88+ large B-cell lymphoma, and patient was initiated on systemic chemotherapy. <h3>Conclusions:</h3> High-resolution OCT has enabled physicians to recognize unique features of different neoplasms such as PCNSL. Our case emphasizes the importance of detailed neuro-ophthalmologic examination and utilization of adjunct tests such as OCT in cases of progressive subacute leukoencephalopathy of unknown etiology. This would also lead to use of less invasive diagnostic methods such as vitreous biopsy instead of brain biopsy, earlier diagnosis, and treatment of patients with PCNSL. <b>Disclosure:</b> Dr. Moheb has nothing to disclose. Dr. Olsen has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for American Academy of Ophthalmology. Dr. Olsen has stock in Non-Medical, unrelated. The institution of Dr. Olsen has received research support from National Eye Institute (NEI). The institution of Dr. Olsen has received research support from Novartis. Dr. Olsen has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Tobin has received research support from Mallinckrodt. Dr. Tobin has received personal compensation in the range of $500-$4,999 for serving as a Speaker with NeurologyLive. John J. Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. John J. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. John J. Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon.

A 33-year-old male patient with progressive leukoencephalopathy, early childhood cataract and recurrent diarrhea

A 33-year-old male patient with progressive leukoencephalopathy, early childhood cataract and recurrent diarrhea

Undiscovered Phenotype of KARS1 Related Mitochondrial Leukoencephalopathy

Background: Infantile onset progressive leukoencephalopathy with or without deafness is an autosomal recessive neurodegenerative disorder with variable clinical presentation, manifesting in infancy or early childhood. This disorders is one of KARS1 gene mutation spectrum that results mostly from compound heterozygous mutations rather than homozygous mutations, resulting in a dysfunctional mitochondrial enzyme. Case presentation: We report our 4-year-old Saudi boy of non-consanguineous parents, with a compound heterozygous mutation in KARS1 gene presenting clinically with speech delay, bilateral sensonural hearing loss, unilateral progressive hemiparesis, iron deficiency anemia and lytic bone lesions. Conclusion: KARS1 mutation has a heterogenous phenotypic presentation, and variable clinical severity. We report a new clinical feature of lytic bone lesions which could potentially expand the phenotype of this genetic disorder spectrum. Early recognition of the clinical presentation is warranted to facilitate diagnosis, prognosis and appropriate family counseling.

Which mass is this? Diagnostic dilemma of an HIV patient presenting with intracranial mass

Patients living with HIV (PLWHA) suffer from many medical condition, neurological complaints being one of the commonest. Intracranial masses are frequently found upon radiological examination on these patients. Differential diagnoses of intracranial mass in these patients vary, with several features overlapping each other, making diagnosis, and thus management, challenging. A patient diagnosed previously with HIV, a woman in her thirties, presented to the ER complaining headache for 2 weeks. Upon examination, she also exhibited left-sided hemiparesis and cranial nerve symptoms. A computed tomography (CT) scan showed multiple contrast-enhancing lesions with meningeal enhancement, which can be attributed to toxoplasmic encephalitis (TE), primary central nervous system lymphoma (PCNSL), progressive multiple leukoencephalopathy (PML), or tuberculous (TB) meningitis. Her toxoplasma serology came up positive, therefore the empirical treatment was focused on eliminating the parasite Toxoplasma gondii, as well as supportive therapy, after which she showed significant improvement in her clinical symptoms as well as brain imaging. Determining the etiology of intracranial mass in HIV patients are not always straightforward; consideration of several factors and administering therapy according to algorithms can deliver good outcome.

Expanded phenotype of AARS1-related white matter disease

Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes. We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.

Clinical Reasoning: A Middle-aged Man With a History of Muscle Pain Presenting With Progressive Leukoencephalopathy and Subsequent Coma.

A 44-year-old left-handed man was admitted in October 2016 for acute-onset tingling and weakness in the left arm, cheek, and tongue and speech difficulties. These symptoms completely disappeared 1 hour later but were followed by several hours of headache, nausea, and vomiting. The patient experienced self-limiting gastroenteritis 2 months earlier. His medical history was unremarkable except for mild muscle pain aggravated by physical activity starting 4 years earlier. He never experienced a migraine, and his family history was negative for neurologic disorders. Neurologic examination was normal. There was no joint swelling, rash, renal impairment, or ocular signs. The working diagnoses were transitory ischemic attacks and migraine with aura. Brain CT and ultrasonography of the carotid arteries were normal.

Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology.

The success of selective B-cells depleting therapies, as the anti-CD20 antibodies, in patients with multiple sclerosis (MS) has confirmed that B-cells are critical in the immune pathogenesis of the disease. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20+ B-cells, profoundly suppresses acute inflammatory disease activity, representing a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS). It is also the first proven therapy able to slow disability progression in primary progressive multiple sclerosis (PPMS), particularly in patients with signs of acute radiological activity before being enrolled. Effectiveness has widely been demonstrated in randomized clinical trials (RCTs), and recently confirmed in open-label extension trials. Here, we review the role of B-cells in MS, the mechanism of action of ocrelizumab, its pharmacokinetics and pharmacodynamics, and the clinical data supporting its use, as well as safety data. We focus on issues related to the maintenance of immunocompetence, essential to ensure an immune response to either a primary infection or a vaccination. Lastly, we discuss about the possible role of ocrelizumab as an exit strategy from natalizumab-treated patients at risk of developing multifocal progressive leukoencephalopathy. In view of using ocrelizumab chronically, collecting long-term safety data and finding strategies to minimize adverse events will be extremely relevant.

Dynamic analysis of CSF1R-related leukoencephalopathy on magnetic resonance imaging: a case report

BackgroundColony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare and rapidly progressive leukoencephalopathy characterized by cognitive, motor, and neuropsychiatric symptoms, which is often misdiagnosed. Magnetic resonance imaging (MRI) signs and follow-up MRI of CSF1R-related leukoencephalopathy could help in establishing a diagnosis, but these features are not widely known by general neurologists.Case presentationA 34-year-old man was admitted for progressive weakness of the right limbs over 8 months. His father and sister had a similar clinical evolution. The primary neurological signs were hemiplegia, cognitive decline, dysarthria, pyramidal signs, ataxia and parkinsonism, and rapid disease progression. Cerebrospinal fluid analysis results were normal. Despite receiving treatment for improving cerebral metabolism and relieving the muscle spasm, his symptoms did not improve significantly. Brain MRI showed lesions concentrated in the corpus callosum and the deep white matter of the bilateral parieto-occipital lobes, periventricular areas, and corticospinal tracts. There was an enhanced lesion after a gadolinium-enhanced MRI scan. Over the 8-month progression, the lesions always exhibited restricted diffusion. The diffuse lesions gradually increased as the disease progressed. Genetic sequencing results showed a novel heterozygous missense mutation (c.2267 T > C p.L756P) in the CSF1R gene. The patient was treated with citicoline and idebenone for 4 days to improve cerebral metabolism, but his symptoms did not improve significantly.ConclusionThe multiple lesions involving the pyramidal tract and white matter showed continuously restricted diffusion on brain imaging and gradually increased with disease progression.

Whole genome and exome sequencing identify NDUFV2 mutations as a new cause of progressive cavitating leukoencephalopathy

BackgroundProgressive cavitating leukoencephalopathy (PCL) is thought to result from mutations in nuclear genes affecting mitochondrial function and energy metabolism. To date, mutations in two subunits of complex I, NDUFS1 and...

An Unusual Case of Progressive Multifocal Leukoencephalopathy in an Immunocompetent Patient Masquerading as a Stroke

Background: Progressive multifocal leukoencephalopathy is a fatal demyelinating condition due to reactivation of latent JC virus in cerebral white matter. Its prevalence is 1in 200,000 and extremely rare in immunocompetent individuals. It can mimic subacute stroke, brain tumours and other demyelinating conditions which have different outcomes. PML typically occurs in an immunocompromised patient, where the archetype JC virus gains pathogenic potential and initiate oligodendroglial inflammation. Currently, the immune reconstitution is considered as the treatment of choice; however, paradoxical worsening with IRIS PML is a significant challenge. There is limited evidence available on how to manage PML in immune competent patients. Direct antiviral agents have no convincing evidence to-date. There is anecdotal evidence that IL-2, filgrastim, and vaccination may be helpful. Case presentation: A 74-year-old man presented with right-sided weakness and dysphasia. He was initially managed as having subacute stroke based on imaging and clinical findings. He subsequently deteriorated, triggering to revisit of the original diagnosis and repeat imaging. He underwent extensive workup, including lumbar puncture and JC viral testing. He was commenced on Mirtazapine to prevent JC viral spread; however, he later passed away. A subsequent post-mortem brain biopsy confirmed the progressive leukoencephalopathy. Conclusion: Even though extremely rare, progressive multifocal leukoencephalopathy should be considered in the differential diagnosis of progressive neurological conditions. It is essential to rule out other treatable conditions as progressive multifocal leukoencephalopathy has a fatal outcome invariably.

Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient.Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis.Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome.Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

One Case Report and Literature Review of Alexander’s Disease Caused by a Mutation in the GFAP Gene

Alexander disease (AxD), the first known hereditary astrocyte disease, is a rare progressive leukoencephalopathy, which is an autosomal dominant genetic disease caused by mutation of GFAP gene encoding glial fibrillary acidic protein. According to the age of onset and clinical manifestations, it can be divided into two types: type I (onset age<4 years) mainly manifest as large head circumference, epileptic seizures, developmental retardation and paroxysmal aggravation, type II has late onset, manifested as autonomic dysfunction, eye movement abnormalities, palatal myoclonus and medulla oblongata symptoms [1].

Clinical and genetic characteristics of 62 children with mitochondrial epilepsy

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA

Ribose 5-phosphate isomerase deficiency is a rare genetic leukoencephalopathy caused by pathogenic sequence variants in RPIA, that encodes ribose 5-phosphate isomerase, an enzyme in the pentose phosphate pathway. Till date, only three individuals with ribose 5-phosphate isomerase deficiency have been described in literature. We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T > C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition.