BPAN manifesting with febrile seizures and language delay: a case report from Brazil

Neurodegeneration with brain iron accumulation (NBIA) is a complex group of hereditary progressive neurodegenerative diseases characterized by deposition of iron in the basal ganglia. Twelve genetic forms of this disorder have been identified in previous studies. Though they have different inheritance mechanisms all are usually associated with abnormal brain MRI findings. One of NBIA types is an X-linked disorder known as Beta-propeller Protein Associated Neurodegeneration (BPAN). Herein we describe the case of a 4-year-old girl with 2 episodes of febrile seizures, a brain MRI showing nonspecific hyperintense signal in the dentate nucleus area, and delays in language and communication development. Her diagnosis was made based on a genetic evaluation where exome sequencing revealed a mutation in the position chrX:48.933.022 region of the WDR45 gene. The literature describes different clinical presentations for BPAN, each with a different prognosis, suggesting a wide range of possible symptoms of BPAN, including mild cognitive delay and even epileptic encephalopathy (EE). (AU)

Analysis of PLA2G6 gene variant in a family affected with infantile neuroaxonal dystrophy / 中华医学遗传学杂志

OBJECTIVE@#To identify potential variant in a child diagnosed as infantile neuroaxonal dystrophy.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the patient and his parents and subjected to next generation sequencing. Suspected variant was verified by PCR and Sanger sequencing. Pathogenicity of the mutation was predicted by using bioinformatic software including SIFT and PolyPhen-2.@*RESULTS@#The child was found to carry compound heterozygous variations c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene, which were respectively inherited from his father and mother. c.2266C>T has changed codon 756 (glutamine) into a stop codon, resulting premature termination of peptide chain synthesis. c.2266C>T has not been reported previously and was predicted to be harmful.@*CONCLUSION@#The compound variants of c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene probably underlies the disease in the child. Above finding has enriched the variant spectrum of the PLA2G6 gene.

Neuroaxonal Dystrophy in a mule: first case reported / Distrofia neuroaxonal em muar: primeiro relato de caso

A 12-month-old mule (sterile hybrid equine species) presented unspecific neurological changes (symmetric ataxia, dysmetria, conscious proprioceptive deficit and weakness). Due to poor prognosis and to the fact that a sibling from the previous generation exhibited similar clinical signs that were not definitively diagnosed, the animal was euthanized. Diagnosis of neuroaxonal dystrophy was confirmed by anatomohistopathological analysis. This is the first clinical case of neuronal dystrophy in a mule reported in the world. The clinical and histopathological characteristics of this disease were very similar to those reported for several equine breeds. Therefore, the disease should also be considered in the diagnosis of neurological conditions in mules and donkeys.(AU)

Relata-se o caso de uma mula de 12 meses que apresentou alterações neurológicas inespecíficas (ataxia simétrica, dismetria, déficit proprioceptivo consciente e fraqueza). Devido ao mau prognóstico e ao fato de um irmão da geração anterior apresentar sinais clínicos similares sem diagnóstico conclusivo, o animal foi eutanasiado. O diagnóstico de distrofia neuroaxonal foi confirmado por análise anátomo-histopatológica. Esse é o primeiro caso clínico de distrofia neuroaxonal em muar relatado no mundo. As características clínicas e histopatológicas dessa doença foram muito semelhantes às relatadas em várias raças de equinos. Portanto, a doença também deve ser considerada no diagnóstico de condições neurológicas em muares e asininos.(AU)

Clinical features of infantile neuroaxonal dystrophy and PLA2G6 gene testing / 中国当代儿科杂志

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease. Two boys aged 3 years and 4 years and 2 months respectively, were admitted to the hospital due to delayed mental and motor development. There were no abnormalities at birth, and both children had low muscle strength and tension on admission. One child was not able to stand alone and had impaired vision. Electromyography showed neurogenic damage, and head MRI revealed cerebellar atrophy. High-throughput sequencing revealed compound heterozygous mutations in the PLA2G6 gene in the two children. The mutations (IVS11-1G>T and c.1984C>G) in one child were new mutations, and immunohistochemistry showed a reduction in the protein expression of PLAG6 in the muscular tissue of this child. INAD has the main clinical manifestations of psychomotor developmental regression and cerebellar atrophy. High-throughput sequencing can help with clinical diagnosis.

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging / Uma orientação diagnóstica para neurodegeneração com acúmulo cerebral de ferro: aspectos clínicos, genéticos e de neuroimagem

ABSTRACT Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

RESUMO A neurodegeneração com acúmulo cerebral de ferro (sigla em inglês NBIA) representa um grupo heterogêneo e complexo de doenças neurodegenerativas hereditárias, caracterizada pelo acúmulo cerebral de ferro, especialmente nos núcleos da base. O quadro clínico das NBIAs em geral inclui distúrbios do movimento, particularmente parkinsonismo e distonia, disfunção cognitiva, sinais piramidais e anormalidades da retina. As formas de NBIA descritas até o momento incluem neurodegeneração associada a pantothenase kinase (PKAN), neurodegeneração associada a phospholipase A2 (PLAN), neuroferritinopatia, aceruloplasminemia, neurodegeneração associada a beta-propeller protein (BPAN), síndrome de Kufor-Rakeb, neurodegeneração associada a mitochondrial membrane protein (MPAN), neurodegeneração associada a “fatty acid hydroxylase” (FAHN), neurodegeneração associada a coenzyme A synthase protein (CoPAN) e síndrome de Woodhouse-Sakati. Esta revisão é uma orientação para o diagnóstico das NBIAs, partindo das características clínicas e achados de neuroimagem, até a etiologia genética.

Neurodegeneration with brain iron accumulation: A case report / Neurodegeneração com acúmulo cerebral de ferro: relato de caso

ABSTRACT Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.

RESUMO Neurodegeneração associada à pantotenato-quinase (PKAN) é uma entidade autossômica recessiva causada pela mutação do gene PANK2. Caracteriza-se por depósito cerebral anormal de ferro, particularmente nos globos pálidos. PKAN faz parte de um grupo de desordens conhecidas como neurodegeneração com acúmulo cerebral de ferro (NBIA). Relatamos um caso de PKAN atípica com sua apresentação mais característica, sendo evidentes sintomas psiquiátricos marcados, distúrbio da fala e distonia focal. A ressonância magnética de crânio possui grande importância diagnóstica neste grupo de desordens, e neste caso, demonstrou o sinal do olho de tigre. O teste genético confirmou o diagnóstico.

What's in a name? Problems, facts and controversies regarding neurological eponyms / O que significa um nome? Problemas, fatos e controvérsias de epônimos em neurologia

ABSTRACT The use of eponyms in neurology remains controversial, and important questions have been raised about their appropriateness. Different approaches have been taken, with some eponyms being excluded, others replaced, and new ones being created. An example is Hallervorden-Spatz syndrome, which has been replaced by neurodegeneration with brain iron accuulatium (NBIA). Amiothoplic lateral sclerosys (ALS), for which the eponym is Charcot’s disease, has been replaced in the USA by Lou Gehrig’s disease. Guillain-Barré syndrome (GBS) is an eponym that is still the subject of controversy, and various different names are associated with it. Finally,restless legs syndrome (RLS), which was for years known as Ekbom’s syndrome, has been rechristened as RLS/Willis-Ekbom syndrome.

RESUMO O uso de epônimos em neurologia permanece ainda controverso nos dias de hoje, e importantes questões tem sido levantadas sobre o seu uso. Diferentes abordagens têm sido feitas, com a exclusão de alguns epônimos, modificação ou criação de outros. Um exemplo é a síndrome de Hallervorden-Spatz (SHS), cuja denominação foi modificada para neurodegeneração associada com acúmulo de ferro cerebral (NBIA). Outro exemplo é a esclerose lateral amiotrófica (ELA), cujo epônimo doença de Charcot, tem sido substituído nos EUA por doença de Lou Gehring. A síndrome de Guillain-Barré (SGB) representa um epônimo em que a controvérsia persiste, e diferentes nomes têm sido associados ao clássico SGB. Por fim, a síndrome das pernas inquietas (SPI), que por anos foi definida como síndrome de Ekbom, e que na atualidade foi definida como SPI/síndrome de Willis-Ekbom.

A novel homozygous mutation in PLA2G6 gene causes infantile neuroaxonal dystrophy in a case / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical symptoms and potential mutations in the PLA2G6 gene for a child with infantile neuroaxonal dystrophy.</p><p><b>METHODS</b>Clinical data of the patient was collected. The coding regions of PLA2G6 gene was subjected to Sanger sequencing using blood DNA from the patient and her parents.</p><p><b>RESULTS</b>The patient has presented with psychomotor regression and hypotonia, followed by development of tetraparesis. A novel homozygous mutation G68A in the PLA2G6 gene was found by DNA sequencing, while her parents were both heterozygous carriers.</p><p><b>CONCLUSION</b>The psychomotor regression and tetraparesis of the patient was caused by infantile neuroaxonal dystrophy due to a novel homozygous mutation in the PLA2G6 gene, which was inherited from her parents.</p>

Three Patients With Classic and Atypical Neurodegeneration With Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is a disorder characterized by various mixtures of extrapyramidal, pyramidal or psychiatric abnormalities associated with iron accumulation in the basal ganglia. The mutations in the pantothenate kinase gene (PANK2) were found in approximately two thirds of the patients with NBIA. We report three patients wtih NBIA, and two of them showed mutations in the PANK2 gene.

Neurodegeneración con acumulación de hierro tipo 1. Revisión de la bibliografía y reporte de un caso / Type 1 neurodegeneration with iron deposition. Case report and literature review

La neurodegeneración con acumulación de hierro tipo 1 (enfermedad de Hallervorden-Spatz) es una entidad rara, que se caracteriza por una disfunción extrapiramidal progresiva y demencia. Usualmente, inicia en la niñez tardía o adolescencia temprana. La enfermedad puede ser esporádica o familiar. En este artículo se presenta el caso de un paciente de 17 años de edad con diagnóstico de Hallervorden- Spatz y con los hallazgos imagenológicos típicos de esta enfermedad.

Distrofia neuroaxonal infantil: relato de dois casos / Infantil neuroaxonal dystrophy: report of 2 cases

Descrevemos dois casos de distrofia neuroaxonal infantil ou doença de Seitelberger, que é doença rara, neurodegenerativa, com herança autossômica recessiva. O primeiro caso, sexo masculino, com 8 anos de idade, apresentava atraso do desenvolvimento psicomotor, ataxia e fraqueza muscular. Ao exame físico foi encontrado nistagmo horizontal e vertical com palidez do disco óptico, hipotonia e arreflexia profunda. O segundo caso, sexo masculino, com 1 ano e 6 meses de idade, apresentava atraso do desenvolvimento psicomotor e convulsões. No exame físico, apresentava atrofia de nervo óptico, hipertonia e hiperreflexia. A biópsia de nervo sural de ambos os pacientes mostrou aumento dos axônios, compátivel com distrofia neuroaxonal. As características clínicas pleomórficas, bem como os achados neurofisiológicos variáveis tornam difícil firmar o diagnóstico, o qual é ajudado pela confirmação anatomopatológica dos esferóides neuroaxomais.

A Case of Infantile Neuroaxonal Dystrophy

We herein report a case of infantile neuroaxonal dystrophy (INAD) with protracted course. The 3 year old patient suffered from ataxia, gait disturbance, oculomotor disturbance, psychomotor regression and bilateral pyramida l tract signs since the age of two. Similar neurological symptoms occurred in his elder brother, beginning at the age of one, who eventually died at the age of four. Magnetic Resonance Imaging (MRI) of the patient showed progressive atrophy of cerebral cortex and cerebellum with diffusely increased T2 signal in bilateral cerebellar hemisphere. The patient's brother revealed similar findings. MRI of the suspected cases may facilitate early diagnosis of INAD, and since it is a well-established autosomal recessive neurodegenerative disaese, early and appropriate genetic counseling of the parents is required.