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ABSTRACT This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.
RESUMO Neste artigo, objetivamos apresentar os achados da tomografia de coerência óptica em uma nova mutação detectada no gene NEU1 em um caso de síndrome macular vermelho-cereja bilateral associada à sialidose tipo 1. Um paciente de 19 anos com um achado de mancha macular vermelho-cereja foi submetido a análises metabólicas e genéticas, apoiadas por imagens de tomografia de coerência óptica de domínio espectral (SD-OCT). Ao exame de fundo de olho, foi observada uma mancha macular vermelho-cereja bilateral. Nas imagens de SD-OCT, observou-se hiper-refletividade nas camadas internas da retina e na camada fotorreceptora na região foveal. Foi realizada uma análise genética e uma nova mutação foi detectada no gene NEU1, resultando em sialidose tipo 1. Nos casos em que é detectada uma mancha vermelho-cereja na mácula, o diagnóstico diferencial de sialidose deve ser feito e mutações do gene NEU1 devem ser rastreadas. A SD-OCT por si só não é suficiente para o diagnóstico diferencial, porque achados de aparência semelhante podem se manifestar em casos de doenças metabólicas da infância.
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Objective:To investigate the clinical features and genetic mutations of microvillus inclusion disease (MVID).Methods:Clinical features and gene sequencing results of a neonate with MVID in Children's Hospital of Chongqing Medical University in August 2019 were retrospectively analyzed. Literature was retrieved up to October 2021, with the terms of microvillus inclusion disease, congenital microvilli atrophy, MVID, MYO5B, STX3, and STXBP2 in China National Knowledge Infrastructure, Wanfang Database, VIP database, and PubMed. Clinical features, diagnosis, and treatment of the reported MVID cases were reviewed. Results:(1) Case report: A male infant presented with jaundice two days after birth and was admitted to our hospital. Clinical features included intractable diarrhea, intermittent abdominal distension, uncorrectable dehydration, and weight loss. Laboratory test results indicated metabolic acidosis, electrolyte disorder, and cholestasis. Whole exome sequencing confirmed the diagnosis of MVID in this baby boy with compound heterozygous mutations of c.1021C>T(p.Q341*) and c.1125G>A(p.W375*) in the MYO5B gene, which were inherited from the father and the mother, respectively. (2) Literature review: Except for the present case, 31 patients from 20 articles were reviewed, and the typical clinical manifestations were intractable diarrhea, accompanied by dehydration, metabolic acidosis, electrolyte disorder, etc. Some patients also developed extra-gastrointestinal symptoms, including feeding difficulties and malnutrition (8/18), respiratory distress syndrome (4/18) and jaundice/cholestasis (4/18) in patients with MYO5B mutations; feeding difficulties and malnutrition (2/5), respiratory distress syndrome (1/5), and sepsis (1/5) in patients with STX3 mutations; feeding difficulties (2/9), respiratory distress syndrome (1/9), jaundice/cholestasis (1/9), sepsis (1/9), and hypoglycemia (1/9) in patients with STXBP2 mutations. In terms of the demographic data and prenatal examination, preterm birth (8/18), fetal bowel dilatation (5/18), polyhydramnios (5/18), parental consanguinity (2/18), and meconium-stained amniotic fluid (2/18) occurred among patients with MYO5B mutations. In those with STX3 mutations, parental consanguinity (3/5), fetal bowel dilatation (1/5), polyhydramnios (1/5), and meconium-stained amniotic fluid (1/5) occurred. Of nine patients with STXBP2 mutations, parental consanguinity (3/9), preterm birth (2/9), and polyhydramnios (2/9) occurred. Conclusions:MVID has atypical clinical features and a high mortality, resulting in difficulty in the diagnosis and treatment. The possibility of MVID should be considered when an infant presents with intractable diarrhea, dehydration, metabolic acidosis, and electrolyte disorder accompanied by multiple extra-gastrointestinal symptoms. Early identification of MYO5B, STX3, and STXBP2 mutations will benefit prompt intervention, prognosis evaluation, and genetic counseling.
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Objective@#To investigate the clinical and genetic characteristics of 3 patients with mucolipidosis and to perform literature review.@*Methods@#A retrospective analysis was made on the clinical data and genetic test results of 3 pedigrees with mucolipidosis. The patients were followed up at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from February 2016 to August 2018. A neonatal inherited metabolic diseases gene panel including GNPTAB, GNPTG, MCOLN1, etc. was used for next-generation sequencing (NGS) based testing. Sanger sequencing was subsequently used to confirm the suspected pathological variants in the patients and their family members. Original papers on mucolipidosis published up to December 2018 were retrieved from PubMed, CNKI and WanFang databases by using the key words "mucolipidosis" AND "Chinese" .@*Results@#The onset ages ranged from (9-90) days. The common clinical characteristics of the 3 patients are developmental delay and skeletal abnormalities. Targeted NGS revealed 5 different variations all in GNPTAB including p.Arg364Ter, p.Ser385Leu, p.Try404Ter, p. Arg587Ter, c.1284+1G>T. Two variants p.Ser385Leu and c.1284+1G>T were novel. Twenty-six cases of mucolipidosis have been reported in Chinese from 8 papers, which included 11 type ML Ⅱα/β, 11 type ML Ⅲ α/β and 4 type ML Ⅲ γ. c.2715+1G>A and p.Arg364Ter variants are likely the hot variants in Chinese ML patients.@*Conclusions@#Mucolipidosis is a rare autosomal recessive disorder characterized by developmental delay and skeletal abnormalities. NGS plus Sanger sequencing detection is effective and accurate for making genetic diagnosis. p.Ser385Leu and c.1284+1G>T of GNPTAB gene are identified as novel pathogenic variants. GNPTAB gene is the main disease causing gene among Chinese ML patients, and c.2715+1G>A and p.Arg364Ter are the most common variants.
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OBJETIVO: Descrever um caso de síndrome de Kinsbourne manifestando-se com quadro de encefalite pós-viral e rever a da literatura. DESCRIÇÃO DO CASO: Criança do sexo feminino, dois anos e seis meses, encaminhada de outro serviço com história de ataxia, irritabilidade e dificuldades articulatórias na fala após episódio prodrômico de febre, lesões de pele e mucosa. Com hipótese de encefalite pós-viral, a avaliação clínica evidenciou quadro de síndrome opsoclônus-mioclonia-ataxia ou síndrome de Kinsbourne. Foi afastada a associação de neuroðblastoma oculto e iniciada terapêutica com corticosteroide. Durante internação e acompanhamento ambulatorial, houve regressão progressiva e normalização do quadro clínico e neurológico inicial. COMENTÁRIOS: Apesar de se tratar de uma doença rara, o diagnóstico de síndrome de Kinsbourne deve ser reconhecido pelos pediatras e intensivistas, com objetivo de instituir traðtamento específico precoce, embora com resultados variáveis, sendo fundamental a exclusão de neuroblastoma oculto.
OBJECTIVE: To describe a case of Kinsbourne syndrome manifesting with signs of post-viral encephalitis, and to review the literature. CASE DESCRIPTION: Female child, aged two years and six months. She was referred from another hospital with a history of ataxia, irritability, and dysphasia after a prodromal episode of fever, skin and mucosa lesions. Referred with suspected post-viral encephalitis, the child was diagnosed with the opsoclonus-myoclonus-ataxia syndrome (Kinsbourne syndrome). The association of occult neuroblastoma was dismissed and therapy with corticosteroids was initiated. During hospitalization and outpatient treatment, there was a progressive regression and normalization of the clinical and neurological original condition. COMMENTS: Albeit a rare disease, the diagnosis of Kinsðbourne syndrome should be recognized by pediatricians and intensivists in order to start an early specific treatment, being important to exclude occult neuroblastomas. The results of the treatment are variable.
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Humans , Female , Child, Preschool , Opsoclonus-Myoclonus Syndrome/complications , Opsoclonus-Myoclonus Syndrome/diagnosis , Dexamethasone/therapeutic useABSTRACT
Tay-Sachs disease is an autosomal recessive disorder of sphingolipid metabolism, caused by enzime hexosaminidase A deficiency that leads to an accumulation of GM2 in neurocytes which results in progressive loss of neurological function. The accumulation of lipid in retinal ganglion cells that leads to a chalk-white appearance of the fundus called "cherry red spot" is the hallmark of Tay-Sachs disease. It is also seen in others neurometabolic diseases as well as in central retinal artery occlusion. This case reports a child with Tay-Sachs disease in a family with four previous similar deaths without diagnostic.
Tay-Sachs é uma doença autossômica recessiva, caracterizada pela deficiência da enzima hexosaminidase A levando ao acúmulo de esfingolipídios (GM2) em células neuronais que resulta em uma perda progressiva da função neurológica. O acúmulo de lipídios em células ganglionais da retina leva a uma aparência de mácula em cereja, característica do fundo de olho de pessoas acometidas. "Mácula em cereja" também pode ser vista em outras doenças neurometabólicas e em oclusão da artéria central da retina. Este trabalho relata o caso de um paciente com doença de Tay-Sachs em uma família com história de quatro óbitos por causas semelhantes sem diagnóstico.
Subject(s)
Humans , Infant , Male , Macula Lutea/pathology , Retinal Diseases/diagnosis , Tay-Sachs Disease/diagnosis , Ophthalmoscopy , Retinal Diseases/etiology , Tay-Sachs Disease/complicationsABSTRACT
We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at 3 years of age. At 5 years of age, a slow neurological deterioration started, associated to visual impairment. Optic atrophy was added to the typical neurological exam ofataxic cerebral palsy and the diagnosis was re-considered. Neuroimaging showed a slow and progressive atrophy of intracerebral structures and ultramicroscopy revealed intracytoplasmatic inclusions in conjunctiva and skin, compatible with mucolipidoses type IV (ML-IV). ML-IV must be included in the differencial diagnosis of cerebral palsy associated with loss of acquired skills and progressive visual impairment. Electrón microscopy of skin or conjunctiva is a useful diagnostic test. Suspicion of ML-IV must not be restricted to Ashkenazi Jewish population.
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Child , Female , Humans , Cerebral Palsy/diagnosis , Mucolipidoses/diagnosis , Chile , Diagnosis, Differential , Indians, South American , Magnetic Resonance Spectroscopy , Mucolipidoses/ethnologyABSTRACT
Lysosomal storage disorders (LSDs) are genetic defects caused by lysosomal hydrolase deficiencies. These deficiencies lead to substrate accumulation affecting cells, tissues and organs. Detecting abnormal compound excretion and deficient enzymes assist diagnosis of these disorders for treatment and prevention. This mini review summarizes clinical presentations and diagnostic workup of LSDs and updates the new development in the area.
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We performed a biochemical study on the patient with mucolipidosis III (ML-III, pseudo-Hurler polydystrophy) in Korea. Confluent fibroblasts from the patient and from normal controls were cultured for 4, 12, 24, 48, and 72 hr, respectively. Lysosomal enzyme activities in culture media after different incubation times and in plasma, leukocytes, and fibroblasts were determined. Most of the leukocyte lysosomal enzymes were within normal limits or slightly lowered; however, plasma lysosomal enzyme activities such as those of hexosaminidase and arylsulfatase A were markedly increased. Numerous phase-dense inclusions were present in the cytoplasm of cultured fibroblasts. Lysosomal enzyme activities of fibroblasts were markedly decreased except for beta-glucosidase. The rates of increase of the lysosomal enzyme activities with incubation time were greater in the culture medium of the patient than in normal control, whereas no difference in the beta-glucosidase activity of the culture media of the patient and the control was found. This study describes the first case of ML-III in Korea, with its typical biochemical characteristics, i.e., a problem with targeting and transporting of lysosomal enzymes which results in a marked increase in plasma lysosomal enzyme activities and a high ratio of extracellular to intracellular lysosomal enzyme activities in cultured fibroblasts.