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A Hemiplegia Alternante da Infância é um distúrbio neurológico grave e uma doença rara (1 em cada 100.000 recém-nascidos), caracterizado por ataques repetidos transitórios de hemiplegia episódica ou tetraplegia que podem durar minutos a horas, acompanhados por outros sintomas paroxísticos como anormalidades oculomotoras e autonômicas, distúrbios do movimento como ataxia, comprometimento cognitivo progressivo, convulsões, distonia e coreia. Os tratamentos atuais são amplamente sintomáticos. Neste relato de caso, apresentamos paciente do sexo feminino, 18 anos, na qual aos 10 meses apresentou o primeiro episódio aparente de crise convulsiva com versão ocular. O eletroencefalograma e tomografia computadorizada não revelaram anormalidades e foram administradas diversas medicações como fenobarbital, carbamazepina, valproato de sódio, topiramato, dicloridrato de flunarizina, clonazepam, cipro-heptadina e pizotifeno, todos sem resultado. Devidos aos sintomas extrapiramidais, paciente passou a utilizar biperideno, apresentando não só melhora da distonia, mas também no número de crises hemiplégicas. Aos 13 anos, ela foi diagnosticada com Hemiplegia Alternante da Infância na mutação patogênica missense de novo c.2415C G (p.Asp805Glu) no gene ATP1A3 apresentando boa resposta ao tratamento com cloridrato de biperideno. (AU)

Alternating hemiplegia of childhood is a severe neurological disorder and a rare disease (1 in 100,000 newborns), characterized by repeated transient attacks of episodic hemiplegia or tetraplegia that can last minutes to hours, accompanied by other paroxysmal symptoms such as oculomotor and autonomic abnormalities, movement disorders such as ataxia, progressive cognitive impairment, seizures, dystonia, and chorea. Current treatments are largely symptomatic. In this case report, we present a female patient, 18 years old, who presented the first apparent episode of seizure with ocular version at ten months of age. The electroencephalogram and CT scan revealed no abnormalities, and several medications such as phenobarbital, carbamazepine, sodium valproate, topiramate, flunarizine dihydrochloride, clonazepam, cyproheptadine and pizotifen were administered, all without result. Due to the extrapyramidal symptoms, the patient started using biperidene, showing improvement in dystonia and the number of hemiplegic seizures. At age 13, she was diagnosed with Alternating hemiplegia of Childhood in the pathogenic missense de novo mutation c.2415C>G (p.Asp805Glu) in the ATP1A3 gene showing a good response to treatment with biperidene hydrochloride. (AU)

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. (AU)Acute hepatic porphyrias (AHPs) are inborn errors of hemebiosynthesis and its most common and severe type is the acute intermittent porphyria (AIP). AIP is an hereditary autosomal dominant disease caused by accumulated porphobilinogen deaminase (PBG) and delta aminolevulin acid (ALA) products. The main symptoms are severe abdominal pain, neuromuscular and psychiatric disturbances, nausea, vomiting, encephalopathy, tachycardia, seizures, tremors and hypertension, that usually are manifested by acute crises. The treatment is based on clinical management and in cases which the patient's quality of life is affected liver transplantation (LT) may be an alternative choice. We report the case of a patient with AHP presenting recurrent crisis leading to chronic symptoms occurrence and poor quality of life with progressive unresponsiveness to hemin treatment. Patient was submitted to LT as curative therapy proposal, but patient still presents some clinical manifestations that may indicate the possibility of a secondary cause to explain persistence of her symptoms despite of biochemical normalization of ALA and PBG. (AU)

As porfirias hepáticas agudas (PHA) compreendem um grupo de porfirias que apresentam erros inatos na biossíntese do grupo heme, sendo a mais severa e o tipo mais comum da PHA, a porfiria aguda intermitente (PAI). A PAI é uma doença autossômica dominante causada pelo acúmulo dos produtos porfobilinogênio deaminase (PBG) e ácido delta-aminolevulínico (ALA). Os principais sintomas são dor abdominal intensa, distúrbios neuromusculares e psiquiátricos, náuseas, vômitos, encefalopatia, taquicardia, febre, tremores e hipertensão, os quais normalmente são manifestados durante as crises agudas. O tratamento é baseado no manejo clínico de todos pacientes durante a crise. Para os casos em que a qualidade de vida do paciente é afetada negativamente, a terapêutica de transplante hepático poderá ser indicada. O objetivo do relato de caso é introduzir o tratamento de uma paciente com recorrentes crises agudas de porfiria e danos em sua qualidade de vida. Uma vez que a paciente não apresentou melhora após tratamento com hematina, foi submetida ao transplante hepático visando a cura da doença. Após o transplante, a paciente ainda apresentou alguns sintomas clínicos, necessitando reformular uma segunda hipótese para explicar a persistência de tais sintomas apesar da normalização dos níveis de ALA e PBG. (AU)

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RESUMO: A hipoventilação relacionada ao sono de origem central resulta em hipercapnia relacionada ao sono na vigência de condições normais do sistema respiratório e excluindo-se outros fatores. Os pacientes portadores dessa patologia podem se apresentar assintomáticos ou com queixas de cefaleia matinal, déficit cognitivo e fadiga, além de eventos como a observação de respiração superficial. No presente relato, descreve-se o caso de uma paciente de três anos, com exame físico geral e neurológico normais, desenvolvimento neuropsicomotor adequado, apresentando irregu-laridades respiratórias e bradicardia durante o sono. Encaminhada para investigação de distúrbios respiratórios do sono, sendo diagnosticada com hipoventilação relacionada ao sono. Através do estudo genético, evidenciou-se a deficiência de biotinidase como a possível causa da sintomatologia, comprovada por dosagens enzimáticas e teste genético molecular. O tratamento medicamentoso foi iniciado precocemente, determinando resolução dos sintomas descritos. A importância do presente relato se encontra na apresentação da deficiência da biotinidase com quadro cardiorrespiratório isolado em criança neurologicamente normal, ademais trata-se de um caso em que a etiologia de Breath-Holding Spells foi a deficiência dessa enzima. Correspondência sugerida pela resolução da hipoventila-ção central após a introdução da biotina. Além disso, nesse caso, os sintomas Apparent Life-Threatening Events, que aterrorizam o observador e até o profissional, foram solucionados com tratamento simples, a ingesta oral de biotina. Esse relato de caso corrobora com a expansão das possibilidades de manifestações fenotípicas das formas tardias de deficiência de biotinidase, como o fenótipo da Síndrome da Hipoventilação Central. (AU)

ABSTRACT: Idiopathic sleep-related hypoventilation occurs in individuals with hypercapnia during sleep in normal conditions of the respiratory system in the absence of other disorders. Patients with this condition may be asymptomatic or have complaints of morning headache, cognitive deficit and fatigue, and observation of shallow breathing. This report describes the case of a 3-year-old patient with normal physical and neurological exam, appropriate neuropsychomotor development, presenting breathing irregularities, and bradycardia during sleep. The patient was referred to an investigation for sleep respiratory disturbs and was diagnosed with hypoventilation related to sleep. The genetic study, done by enzymatic dosages and molecular genetic tests, showed the deficiency of biotinidase as a possible cause of symptomatology. The drug treatment was initiated early with the resolution of the symptoms. The present clinical report highlights the biotinidase deficiency with an isolated cardiorespiratory condition in a neurologically normal child, which also led to Breath-Holding Spells. This relation was suggested after central hypoventilation resolution following biotin introduction. Besides, Apparent Life-Threatening Events symptoms, which terrify the observer and even professionals, disappeared after the oral intake of biotin. Finally, this case report corroborates the expansion of possibilities for the phenotypic manifestations of late cases from biotinidase deficiency, as the SHC phenotyp. ((AU)

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The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.jpainsymman.2018.03.023. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

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Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15-50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%-5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease-causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele. The aim of this study was to describe the first fully penetrant SCA8 family showing mixed Brazilian African and Amerindian origin. Eight members of this family were evaluated-the mother and seven offspring-through a complete neurological examination conducted at the Neurogenetics Clinic, HCFMRP-USP in Brazil. The number of CTA/CTG repeats was obtained after polymerase chain reaction (PCR) and fragment analysis. The haplotype analysis was conducted using a microsatellite marker, D13S1296, and four single nucleotide polymorphisms (SNPs), rs1831189, rs8002227, rs11841483, and rs72284461, all spanning a 70.1 Mb region on chromosome 13q21.3. The molecular analysis showed that the expansions ranged from 104 to 109 CTA/CTG repeats in the six affected individuals and were absent in two asymptomatic daughters (aged 53 and 40 years). Three SNPs cosegregate with the expanded alleles, confirming the connection between expansion and disease in this family. As the SCA8 diagnosis demands careful interpretation, we suggest the use of linkage analysis to observe segregation of the mutation, making more accurate its genotyping.

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UNLABELLED: Mucolipidosis II and III (MLII and MLIII) alpha/beta are rare autosomal recessive lysosomal storage diseases (LSDs) caused by pathogenic variations in the GNPTAB gene. GNPTAB gene codes for the α and ß subunits of phosphotransferase, the enzyme responsible for synthesis of the mannose-6-phosphate (M6P) marker that directs lysosomal enzymes to the lysosome. OBJECTIVES: The objective of this study is to identify sequence variations of the GNPTAB gene in Brazilian patients with MLII and MLIII alpha/beta. METHOD: Sequencing of the GNPTAB gene was performed in samples of gDNA extracted from the peripheral blood of patients with MLII/III diagnosed at a national reference center for LSDs. RESULTS: Twelve unrelated patients, from several regions of Brazil, were included in this study. Only one was born of consanguineous parents. All patients were found to carry at least one nonpathogenic variation. Nine causal sequence variations were found: c.242G>T (p.W81L); c.1123C>T (p.R375X); c.1196C>T (p.S399F); c.1208T>C (p.I403T); c.1514G>A (p.C505Y); c.1759C>T (p.R587X); c.2808A>G (p.Y937_M972del, novel mutation); c. 2269_2273delGAAAC (p.E757KfsX2, novel mutation); and c.3503_3504delTC (p.L1168QfsX5). Both pathogenic variations were identified in 8 of 12 patients; in four patients, only one pathogenic variation was identified. Mutation c.3503_3504delTC, located in exon 19, was the most frequent pathogenic variation found (n=11/24 alleles). The deleterious effect of the c.2808A>C mutation on splicing was confirmed by cDNA analysis. DISCUSSION/CONCLUSIONS: Our findings confirm that the GNPTAB gene presents broad allelic heterogeneity and suggests that, in Brazilian ML II and III patients, screening for mutations should begin at exon 19 of the GNPTAB gene. Further analyses will be conducted on patients in whom both pathogenic mutations have not been found in this study.

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