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Since the outbreak of novel influenza A (H1N1) in 2009, various neurologic complications have been cited.1 A 2-month-old girl died of a rapidly progressive encephalopathy after influenza infection. MRI, performed after 12 hours from the onset of symptoms, showed bilateral and symmetric lesions including the thalamus, the cortical–subcortical regions of the occipital and parietal lobes, and brainstem tegmentum …

Thyroid storm (TS) is rare in pediatrics, most cases reported in literature responded well to medical therapy. We report the case of an adolescent female presented with TS refractory to anti-thyroid medical management. She had refractory hypertension, tachycardia, and progressive encephalopathy despite aggressive medical management. She underwent subtotal thyroidectomy after 2 weeks of failed medical management with a complete resolution of symptoms within days of surgery. We also learned sodium nitroprusside with its direct vasodilatory effect on conduit vessels, verapamil with its rate control properties, and labetalol with its dual sympathetic blockage property were beneficial in the management of this patient.

We are grateful to the patient families for their participation. This research was conducted through intramural funds (RAC# 2120022, 2180004, 2110006) provided by King Faisal Specialist Hospital and Research Centre (KFSHRC). We would like to thank National Plan for Science, Technology and Innovation program under King Abdulaziz City for Science and Technology (NSTIP/KACST) for supporting NK and DC. We thank the King Salman Center for Disability Research for generous funds for NK. We thank the KFSHRC Genotyping and Sequencing Core Facilities at Genetics Department, Research Advisory Council Committees, Saudi Human Genome Program and Purchasing Department (Mr. Faisal Al Otaibi) for facilitating and expediting our requests. The research by STA was supported by funding from King Abdullah University of Science and Technology (KAUST) through the Award No. FCC1/1976-25 form the Office of Sponsored Research. TSB is supported by the Netherlands Organization for Scientific Research (ZonMW Veni, Grant 91617021), a Brain & Behavior Research Foundation NARSAD Young Investigator Grant, an Erasmus MC Fellowship 2017 and Erasmus MC Human Disease Model Award 2018.

Autoimmune encephalitis (AIE) is a rare, severe, and rapidly progressive encephalopathy, and its diagnosis is challenging, especially in adolescent populations when the presentation is mainly psychiatric. Currently, cerebral 18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging is not included in the diagnosis algorithm. We describe a 16-year-old patient with probable seronegative encephalitis with catatonia for which several cerebral PET scans were relevant and helpful for diagnosis, treatment decision making, and follow-up monitoring. The patient recovered after 2 years of treatment with etiologic treatment of AIE and treatment of catatonia. This case suggests a more systematic assessment of the clinical relevance of 18F-FDG-PET imaging in probable seronegative AIE.

In this report we present a clinical case of trismus. The patient in question showed symptoms of trismus for 3 days, rapidly leading to respiratory insufficiency. Afterwards she developed myoclonus and progressive encephalopathy. Neurological workup showed no relevant abnormalities. A CT of the abdomen revealed a mass in the lower abdomen, which turned out to be an ovarian teratoma. Progressive encephalopathy with rigidity and myoclonus (PERM) was diagnosed clinically. Treatment with corticosteroids, benzodiazepines, and levetiracetam did not ameliorate the patient’s condition. Only after the introduction of plasmapheresis was there a spectacular improvement in her clinical state. In this case we could not detect associated antibodies. The most likely cause of PERM is paraneoplastic disease secondary to ovarian teratoma. This type of tumor has been associated with multiple paraneoplastic neurological conditions, but this is the first case associated with PERM. To date there is only one publication on trismus as a sole presenting sign, with a quite similar disease course.

A Woman with Fever, Headache, and Progressive Encephalopathy A 70-year-old woman with a history of migraines was admitted to the hospital in autumn because of fever, headache, and encephalopathy. M...

Leigh syndrome (LS) is a mitochondrial progressive encephalopathy characterized by bilateral symmetric necrotic lesions of the central nervous system. Maternally inherited Leigh Syndrome (MILS) represents 10–20% of LS. Mutations in MT-ATP6 are the most common, being m.8993T > C/G the classical mutations. Molecular diagnosis for mitochondrial diseases is always a challenge and Multiplex ligationdependent probe amplification (MLPA) of mitochondrial DNA can be an initial test for molecular diagnosis, although it is not widely used. We present a MILS patient in which MLPA was able to detect the common m.8993 T > G mutation and serve as a first approach for the definite molecular diagnosis. Fil: Mayorga, Lía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Cueto, Juan Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Correa, Adriana P.. Hospital Pediátrico A. Fleming; Argentina Fil: Guillamondegui, María J.. Hospital Pediátrico A. Fleming; Argentina Fil: Loos, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Araoz, Verónica H.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Laurito, Sergio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Roqué, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina

Diagnostic and treatment delay of Wernicke encephalopathy (WE) is an unfavorably common occurrence owing to its variable clinical presentations. The clinical and imaging features of atypical (nonalcoholic) WE in particular, overlaps considerably with metronidazole induced encephalopathy (MIE), which may further complicate diagnosis and management. We discuss the case of a nutritionally deficient, nonalcoholic male with progressive encephalopathy and significant metronidazole use who presented with features of both WE and MIE. Increased vigilance for these conditions in patients with non-specific neurologic signs is critical for timely diagnosis to prevent irreversible cognitive dysfunction or death.

Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2 that encodes the mitochondrial arginine-tRNA synthetase enzyme (mtArgRS). The clinical presentation overlaps that of PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia and Optic atrophy). The proband presented with severe intellectual disability, epilepsy with varying seizure types, optic atrophy, axial hypotonia, acquired microcephaly, dysmorphic features and progressive cerebral and cerebellar atrophy and delayed myelination on MRI. The presentation had resemblance to PEHO syndrome but sequencing of ZNHIT3 did not identify pathogenic variants. Subsequent whole genome sequencing revealed novel compound heterozygous variants in RARS2, a missense variant affecting a highly conserved amino acid and a frameshift variant with consequent degradation of the transcript resulting in decreased mtArgRS protein level confirming the diagnosis of PCH6. Features distinguishing the proband's phenotype from PEHO syndrome were later appearance of hypotonia and elevated lactate levels in blood and cerebrospinal fluid. On MRI the proband presented with more severe supratentorial atrophy and lesser degree of abnormal myelination than PEHO syndrome patients. The study highlights the challenges in clinical diagnosis of patients with neonatal and early infantile encephalopathies with overlapping clinical features and brain MRI findings.

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Rationale: Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 is an infantile, lethal neurometabolic disorder caused by a NAD(P)HX epimerase (NAXE) gene mutation. It is characterized by a fluctuating disease course with repeated episodes of improvement and regression. In this report, we present a rare case of NAXE gene mutation-related encephalopathy with unexpected neurological recovery and long survival time. Patient concerns: A 20-month-old girl presented with progressively unsteady gait and bilateral hand tremors after a trivial febrile illness. Her disease rapidly progressed to consciousness disturbance, 4-limb weakness (muscle power: 1/5 on the Medical Research Council scale), and respiratory failure. The patient gradually recovered 2 months later. However, another episode of severe fever-induced encephalopathy developed 2 years after the initial presentation. Diagnoses: Results of laboratory investigations, including complete blood count, blood chemistry, inflammatory markers, and cerebral spinal fluid analysis were unremarkable. Electroencephalography and nerve conduction velocity studies yielded normal results. Brain magnetic resonance imaging on diffusion-weighted imaging revealed abnormal sysmmetric hyperintensity in the bilateral middle cerebellar peduncles. A genetic study using whole exome sequencing confirmed the diagnosis of NAXE gene mutation-related encephalopathy. Interventions: Pulse therapy with methylprednisolone, intravenous immunoglobulin, coenzyme Q10, and carnitine were initially introduced. After a NAXE gene defect was detected, the vitamin B complex and coenzyme Q10 were administered. A continuous rehabilitation program was also implemented. Outcomes: NAXE gene mutation-related encephalopathy is usually regarded as a lethal neurometabolic disorder. However, the outcome in this case is better than that in the previous cases. She showed progressive neurological recovery and a longer survival time. The muscle power of the 4 limbs recovered to grade 4. At present (age of 5.5 years old), she can walk with an unsteady gait and go to school. Lessons: Although NAXE gene mutation-related encephalopathy is rare, it should be considered as a differential diagnosis of early onset progressive encephalopathy.

Nutritional deficiencies related neurological manifestations are not uncommon in infants and children. Here, we describe an infant with Vitamin B12 deficiency due to depleted maternal Vitamin B12 status presenting with progressive encephalopathy and extrapyramidal signs. Diagnosis of infantile tremor syndrome was established in our patient based on the clinical and biochemical parameters. Magnetic resonance imaging had shown frontotemporal atrophy with widened Sylvian fissures and prominent cerebrospinal fluid spaces. Clinical and imaging findings might create a diagnostic dilemma with glutaric aciduria type I. Knowledge and identification of infantile tremor syndrome are essential, as it is a potentially treatable disorder. Our patient had significant developmental gains with Vitamin B12 treatment and infant stimulation program. Vitamin B12 deficiency must be looked for as a cause of neuroregression in children hailing from low socioeconomic status, infants of vegetarian mother, and infants with delayed or improper weaning. Screening for Vitamin B12 deficiency is essential in all infants and children with unexplained neuroregression, as this disorder is potentially treatable. More population-based studies in India are needed to explore the prevalence of Vitamin B12 deficiency in pregnant and lactating women and also to assess the need for Vitamin B12 supplementation during pregnancy and lactation.

Introduction: The jequirity bean (Abrus precatorius) seed contains abrin, a toxalbumin, that irreversibly binds the 60-s ribosomal subunit inhibiting protein synthesis. Neurologic manifestations of...

Objective: The study aimed to ascertain different causes and outcomes of convulsive status epilepticus in children. Methods: From January 2018 to June 2018, seventy three patients who presented with status epilepticus were studied. Data were recorded with the help of a pre-formed performa. Etiological factors and outcomes in terms of recovery, morbidity and mortality were studied. Results: Out of 73 children, forty one (56%) were males and 32(44%) were females with median age of 1.09±0.27 years. Etiologies were acute symptomatic 25(34%), febrile 19(26%), progressive encephalopathy 10(14%), remote symptomatic 10(14%) and idiopathic 7(9%) with p-value 0.005. Status epilepticus was controlled within one hour in 42(57%), within 1-6 hours in 21(29%) and more than 6 hours in 10(14%) patients with p-value 0.027. During hospitals stay, twenty one (29%) patients recovered completely, seizure recurred in 12(16%), Twelve (16%) became mentally retarded, Twelve (16%) developed mental retardation along with seizures and 16(22%) died. Eight (10.9%) deaths were attributed to acute symptomatic etiology with p-value less than 0.001. Conclusion: This study concluded that acute symptomatic etiology was more common cause of status epilepticus as compared to other etiologies and it is associated with poorer outcomes as compared to other etiologies. doi: https://doi.org/10.12669/pjms.35.3.120 How to cite this:Uzair M, Ibrahim A, Zafar F, Sultan T. Etiology and outcomes of convulsive status epilepticus in children. Pak J Med Sci. 2019;35(3):620-623. doi: https://doi.org/10.12669/pjms.35.3.120 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) refers to neurological or psychological manifestations, in which headaches and seizures are the most common clinical features...

This study aims to report a one-session endodontic treatment of a patient with chronic Non-progressive encephalopathy (CNPE). A patient with CNPE attended our postgraduate clinic for patients with special needs. During the anamnesis, the patient's brother, who is his legal representative, reported discomfort with the esthetics of the patient's anterior tooth and that the patient felt discomfort when touching the same dental element. After detailed anamnesis and elaboration of the treatment plan, endodontic treatment of element 11 (upper right central incisor) and coronary reconstruction were performed. Taking care of patients with cerebral palsy is still a challenge in dentistry. This is because care has to be taken when carrying out necessary interventions in these patients. This treatment aims at the positive resolution of their pathological condition and well-being. The possibility of endodontic treatment in a single session makes treatment more humane and less mutilating. Este trabajo tiene como objetivo informar sobre un tratamiento endodóntico de una sesión de un paciente con encefalopatía crónica no progresiva (CNPE). Un paciente con CNPE acudió a nuestra clínica de posgrado para pacientes con necesidades especiales. Durante la anamnesis, el hermano del paciente, quien es su representante legal, refirió malestar con la estética del diente anterior del paciente y que el paciente sintió malestar al tocar el mismo elemento dental. Tras una anamnesis detallada y elaboración del plan de tratamiento, se realizó tratamiento endodóntico del elemento 11 (incisivo central superior derecho) y reconstrucción coronaria. La atención al paciente con parálisis cerebral aún es un desafío en la Odontología. Esto se debe a que hay que tener cuidado al realizar las intervenciones necesarias en estos pacientes. Este tratamiento tiene como objetivo la resolución positiva de su estado patológico y su bienestar. La posibilidad de un tratamiento de endodoncia en una sola sesión hace que el tratamiento sea más humano y menos mutilador. Esse estudo objetiva relatar o tratamento endodôntico de uma sessão em paciente com encefalopatia não progressiva crônica (CNPE). Um paciente com CNPE atendeu nossa clínica de pós-graduação para pacientes com necessidades especiais. Durante a anamnese, o irmão do paciente, que é seu representante legal, relatou desconforto com a estética do dente anterior do paciente e que o paciente sentia desconforto ao tocar o mesmo elemento dentário. Após detalhada anamnese e elaboração do plano de tratamento, foi realizado tratamento endodôntico do elemento 11 (incisivo central superior direito) e reconstrução coronariana. O atendimento ao paciente com paralisia cerebral ainda é um desafio na Odontologia. Isso ocorre porque é preciso ter cuidado ao realizar as intervenções necessárias nesses pacientes. Este tratamento visa a resolução positiva do seu estado patológico e bem-estar. A possibilidade de tratamento endodôntico em uma única sessão torna o tratamento mais humano e menos mutilador.

Rapidly progressive encephalopathy in an HIV-positive patient presents a major diagnostic and management challenge. CD8+ encephalitis is a severe but treatable form of HIV-related acute encephalopathy, characterised by diffuse perivascular and intraparenchymal CD8+ lymphocytic infiltration. It can occur in patients who are apparently stable on antiretroviral treatment and probably results from viral escape into the central nervous system. Treatment, including high-dose corticosteroids, can give an excellent neurological outcome, even in people with severe encephalopathy and a very poor initial neurological status. We report a woman with CD8+ encephalitis, with a normal CD4 count and undetectable serum viral load, who made a good recovery despite the severity of her presentation.

Creutzfeldt-Jakob disease is a fatal and untreatable neurodegenerative disorder that is part of the so-called spongiform encephalopathies, which is caused by the abnormal accumulation of PrP protein (called PrPSc) in the central nervous system. The most common human prion disease is sporadic form of Creutzfeldt-Jakob, whose appearance has been associated with environmental effects or unknown and random genetic events that result in the spontaneous production of PrP in the brain. In this work we will present two Clinical cases of two woman who visited the emergency room of the hospital Universitario San Ignacio, in which a rapidly progressive encephalopathy caused by Creutzfeldt-Jakob disease is suspected.

We describe a 4-year-old male child born to non-consanguineous Spanish parents with progressive encephalopathy (PE), microcephaly, and hypertonia. Whole exome sequencing revealed compound heterozygous BRAT1 mutations [c.1564G > A (p.Glu522Lys) and c.638dup (p.Val214Glyfs*189)]. Homozygous and compound heterozygous BRAT1 mutations have been described in patients with lethal neonatal rigidity and multifocal seizure syndrome (MIM# 614498). The seven previously described patients suffered from uncontrolled seizures, and all of those patients died in their first months of life. BRAT1 acts as a regulator of cellular proliferation and migration and is required for mitochondrial function. The loss of these functions may explain the cerebral atrophy observed in this case of PE. This case highlights the extraordinary potential of next generation technologies for the diagnosis of rare genetic diseases, including PE. Making a prompt diagnosis of PE is important for genetic counseling and disease management.

Development of acute neurological symptoms secondary to cerebral oedema is well described in diabetic ketoacidosis (DKA) and often has a poor prognosis. We present the clinical and radiological data of a 17-yr-old girl who developed cortical blindness, progressive encephalopathy, and seizures caused by posterior reversible encephalopathy syndrome (PRES) that developed after her DKA had resolved. Vasogenic oedema in PRES resolves if the underlying trigger is identified and eliminated. In this case, hypertension was identified as the likely precipitating factor and following treatment her vision and neurological symptoms rapidly improved. We suggest how recent DKA may have contributed to the development of PRES in this patient.

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is a genetic neurological condition characterized by extreme cerebellar atrophy. PEHO-Like syndrome is comparable to PEHO syndrome, with the exception that there is no typical neuro-radiologic or neuro-ophthalmic findings. PEHO spectrum disorders are highly clinically and genetically heterogeneous, and this has challenged their diagnosis. This scoping review aims to summarize and discuss common clinical and genetic features of these syndromes to help future researches. This study was performed according to a six-stage methodology structure and PRISMA guideline. A systematic search of seven databases was performed to find eligible publications prior to June 2020. Articles screening and data extraction were independently performed by two reviewers and quantitative and qualitative analyses were conducted. Thirty-eight articles were identified that fulfill the inclusion criteria. Cerebellar atrophy was the main clinical difference between the two groups but data on optic atrophy and infantile spasms/hypsarrhythmia were not consistent with the previously essential diagnostic criteria. Genetic analysis was performed in several studies, leading to identification of pathogenic variants in different genes that caused these conditions due to different mechanisms. Genetic studies could revolutionize the diagnosis process and our understanding of the etiology of this challenging group of patients by providing targeted sequencing panels and exome- or genome-scale studies in the future.

Anti-NMDA receptor encephalitis (NMDARE) was described in 2005 as a syndrome of acute psychosis followed by progressive encephalopathy. Later, it was found to be a paraneoplastic process occurring in young women with teratomas.1 Today, it is recognized as one of the most common nonviral causes of encephalitis overall. In children, the disorder is less commonly associated with malignancy,2 and presents with personality changes, behavioral problems, seizures, dyskinesia, and speech problems.2,3 The condition is often treatment-responsive; however, it can infrequently progress to death after weeks or months despite treatment.4 Mortality is generally lower in children5 and we are not aware of a report of NMDARE that progressed to death within a few days.

Acute liver failure is a rare but life-threatening disease that can lead to progressive encephalopathy, intracranial hypertension, and multiorgan failure. In the developed world, the most common cause remains acetaminophen overdose, but there are still many cases in which there is acute liver failure of unknown etiology. The mainstay of acute liver failure management remains supportive care in the critical care setting. If supportive treatment does not stabilize the disease process, the patient may require emergent liver transplantation. This article summarizes the current management of acute liver failure.

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare treatable autosomal recessive neurometabolic disorder characterized by progressive encephalopathy that eventually leads to severe disability and death if not treated with biotin and thiamine supplements. Objectives: We aimed to determine the optimal management of BTBGD presenting in acute encephalopathic episodes. Method: Case report. Results: An 8-year-old girl born to consanguineous parents was diagnosed with BTBGD at the age of 3 years after presenting with acute encephalopathy and ataxia. The patient was treated with biotin and thiamine, and the family was instructed to continue these medications for life. When she was 7 years old, her supplements were stopped for 2 weeks for social reasons. Afterward, the patient began to have tremor in both hands and an unsteady gait. The family then resumed the medications at the usual dosages. However, the patient remained symptomatic. The patient was admitted with acute BTBGD because of discontinuation of medications. The patient’s condition was then managed with high doses of intravenous thiamine and oral biotin. She showed gradual improvement after 48 hours. She was then discharged home 1 week later with residual mild upper and lower limb tremor, as well as right lower limb dystonia. Further follow-up showed a good neurological condition with no apparent long-term sequel. The family was further educated about the importance of strict compliance. Conclusion: Patients with BTBGD should remain on lifelong treatment with thiamine and biotin. For those who present with acute relapse, we recommend inpatient treatment with high doses of intravenous thiamine and oral biotin. Further clinical research is required to determine the optimal doses and durations.

Aims Post-malaria neurological syndrome (PMNS) is described as a rare post-infectious encephalopathy occurring within two months of resolved malaria infection and with an aparasitaemia. PMNS encompasses three separate neurological syndromes: A delayed cerebellar syndrome, an acute demyelinating polyneuropathy (GBS) and an acute disseminated encephalopathy (ADEMs). Here, we report the first Irish paediatric case of falciparum PMNS, in a patient of African origin, born and living in Ireland. A 15 year old boy presented with a 3 day history of progressive encephalopathy, features of raised ICP and seizures on a background of falciparum malaria treated six weeks previously. PMNS was diagnosed after further investigations and an aparasitaemia. He was sedated and intubated for 2 days and commenced on antimicrobials, antimalarial and steroids. His investigations results as following: MRI brain: Cerebral oedema and optic neuritis, EEG: Severe encephalopathy. Serial thick and thin films: No malaria parasites Falciparum Protein Antigen (RDT): Positive (Can remain positive for 6 weeks after malaria). CSF Studies: Protein 1383 g/dl, 16 WBCs/dl, 100% mononuclear cells). PCRs: negative for HSV, Adenovirus, Coxsackie, EBV, CMV, Meningococcus, Pneumococcus. By day 6 of admission he had made a full recovery with no neurological deficits. Methods Using Google and PubMed, we searched for relevant case reports and journal articles describing neurological syndromes occurring post infection with falciparum malaria in the paediatric population. Results Whilst the prevalence of PMNS (plasmodium falciparum) is 0.12% in adults, the prevalence in children remains unknown. In 1996, a Vietnamese study conducted over 4 years reported 23 patients with PMNS following full recovery from falciparum malaria. Of these, only 3 were children. A 2015 case report describes a further two children with falciparum PMNS. There have been no further paediatric cases reported to date worldwide. Conclusion In conclusion, PMNS is an increasingly recognised, but rare complication of malaria that must be differentiated from relapsing or recurrent malaria, and post-infectious neurological syndromes, e.g. ADEM. In particularly severe cases, steroids have been given as an adjunctive therapy to speed recovery however PMNS is a self-limiting condition that resolves within 2–14 days and requires no specific treatment.

Intellectual disability is an important health issue, with a prevalence estimated at 1%. Autosomal genes are increasingly identified as an important cause, although still few of them are known. Most cases are of recessive origin and are found in large consanguineous families in the Middle East. Mutations in the TRAPPC9 gene have been reported in different families and are associated with a nonsyndromic form of intellectual disability, although phenotypic abnormalities such as a specific facial appearance, obesity, hypotonia and consistent brain abnormalities were linked to these mutations. Here, we describe three siblings of consanguineous Algerian parents with a homozygous c.1708C>T, p. Arg570* mutation in the TRAPPC9 gene. Initially a relatively normal development was seen until the age of 12-18 months, with from then on a progressive degradation of their mental and motor state and the presence of convulsions in two of them. This, in combination with progressive white matter lesions seen on repetitive magnetic resonance imaging, suggests that this TRAPPC9 mutation should not only be considered as a form of intellectual disability, but also as a neurodegenerative disease.

Celia's Encephalopathy (MIM #. 615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers.