RESUMO
Hypomelanosis of Ito (HMI) is part of a neuroectodermal syndrome characterized by distinctive skin manifestations with or without multisystemic involvements. In our undiagnosed diseases program, we have encountered a 3-year-old girl presenting with characteristic skin hypopigmentation suggesting HMI and developmental delay. An exome and genome approach utilizing next-generation sequencing revealed a heterozygous de novo frameshift variant in the KIF13A gene, i.e., NM_022113.6: c.2357dupA, resulting in nonsense-mediated decay. The low mutant allelic ratio suggested that the mutation has occurred postzygotically leading to embryonic mosaicism. Functionally, K1F3A regulates cell membrane blebbing and migration of neural crest cells by controlling recycling of RHOB to the plasma membrane and is also involved in melanosome biogenesis. Importantly, hypopigmentation of the skin has been reported in chr 6p22.3-p23 microdeletion syndrome supporting the association of KIF13A haploinsufficiency with the novel neuroectodermal syndrome. With the increased availability of genome sequencing, we envisage more genetic causes of HMI will be identified in the future.
Assuntos
Cromossomos Humanos Par 6 , Mutação da Fase de Leitura , Hipopigmentação/genética , Cinesinas/genética , Síndromes Neurocutâneas/genética , Zigoto , Pré-Escolar , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mosaicismo/embriologia , Síndromes Neurocutâneas/patologia , Sequenciamento do ExomaRESUMO
BACKGROUND AND AIMS: The prognostic role of noninvasive assessments of liver fibrosis has been evolving. Our aim was to investigate the prognostic value of liver stiffness measurement (LSM) with transient elastography and serum-based Hui index to predict hepatic events and deaths in chronic hepatitis B (CHB) patients. METHODS: The main prospective cohort included 1555 consecutive CHB patients referred for transient elastography examination; a subgroup of 980 patients underwent follow-up assessments at least 3 years later formed the serial cohort. Cox proportional hazard model was performed to determine the relationship of LSM, Hui index and other clinical variables with hepatic events and deaths. RESULTS: During a mean follow-up of 69 ± 9 months, 119 patients (7.6%) developed hepatic events or deaths. Hepatic event-free survival was significantly decreased with increasing stages of LSM and Hui index. The 5-year cumulative probability of hepatic event-free survival of patients of Stage 1-7 of LSM were 99.3%, 98.8%, 95.7%, 90.9%, 89.6%, 74.6%, and 50.0%, respectively; that of Stage 1 to 3 of Hui index were 98.2%, 93.1%, and 77.5%, respectively. Independent predictors of hepatic event-free survival were age, baseline LSM, and follow-up Hui index. Serum ALT and body mass index affected the accuracy of prediction by LSM. Patients remained early stages of LSM or Hui index at follow-up visit had better survival compared to those remained at late stages. CONCLUSION: Baseline and change in noninvasive parameters of liver fibrosis, LSM and Hui index, are accurate to predict hepatic event-free survival in CHB patients.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/complicações , Hepatite B Crônica/mortalidade , Cirrose Hepática/diagnóstico , Transaminases/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores de TIE , Índice de Gravidade de DoençaRESUMO
BACKGROUND & AIMS: CU-HCC score is accurate to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, diagnosis of cirrhosis may be incorrect based on ultrasonography, leading to some errors in HCC prediction. This study aimed to evaluate the accuracy of LSM-HCC score, refined from CU-HCC score with liver stiffness measurement (LSM) using transient elastography to predict HCC. METHODS: A prospective cohort study of 1555 consecutive CHB patients referred for transient elastography examination; 1035 and 520 patients randomly assigned to training and validation cohorts, respectively. Clinical cirrhosis of CU-HCC score was substituted by LSM and analyzed with multivariable Cox regression analysis with other parameters. RESULTS: During a mean follow-up of 69 months, 38 patients (3.7%) in the training cohort and 17 patients (3.4%) in the validation cohort developed HCC. A new LSM-HCC score composed of LSM, age, serum albumin and hepatitis B virus (HBV) DNA levels were derived, which ranges from 0 to 30. Areas under receiver operating characteristic curves of LSM-HCC score were higher than those of CU-HCC score (0.83-0.89 vs. 0.75-0.81). By applying the cutoff value of 11, the score excluded future HCC with high negative predictive value (99.4%-100%) at 5 years. CONCLUSIONS: LSM-HCC score constructed from LSM, age, serum albumin and HBV DNA level is accurate to predict HCC in CHB patients.
Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/fisiopatologia , Neoplasias Hepáticas/etiologia , Adulto , Idoso , Estudos de Coortes , DNA Viral/sangue , Técnicas de Imagem por Elasticidade , Feminino , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
Background: Strychnine poisoning is rare but possibly fatal. The most reported sources of strychnine poisoning include rodenticides and adulterated street heroin. Here we report a case series of an unusual cause of strychnine poisoning - Strychnisemen, a herb known as "maqianzi" in traditional Chinese medicine (TCM). Methods: All cases of strychnine poisoning confirmed by the Hospital Authority Toxicology Reference Laboratory (HATRL, the highest-level clinical toxicology laboratory in Hong Kong) between May 2005 and May 2018 were reviewed. Results: Twelve cases of strychnine poisoning were recorded, and Strychni semen was the exclusive source. Ten (83.3%) patients presented with muscle spasms, and four (33.3%) developed typical conscious convulsions. The poisoning was severe in two (16.7%) patients, moderate in three (25%) and mild in eight (58.3%). No case fatality was recorded. Three (25%) patients were TCM practitioners and two (16.7%) were laymen who bought the herb themselves without a proper prescription. Conclusion: The practice of TCM is becoming popular in different parts of the world amid the COVID-19 pandemic. The spectrum of clinical features of strychnine poisoning secondary to Strychni semen are similar to those arising from different origins. Eliciting a history of TCM use, apart from exposure to rodenticides and drugs of abuse, may allow timely diagnosis in patients with compatible clinical features. Enhancement of TCM safety could minimize the hazard.
Assuntos
COVID-19 , Estricnina , Humanos , Medicina Tradicional Chinesa , Pandemias , SARS-CoV-2 , Estricnina/efeitos adversosRESUMO
With their potent anti-inflammatory effects, corticosteroids are popular adulterants in illicit health products for allergies, dermatitis and pain control. Their illegal supply over the counter is also a common practice for similar conditions. Prolonged, unsupervised usage of corticosteroids often leads to severe adverse effects including Cushing syndrome, adrenal insufficiency and immunosuppression. Confirming clinical suspicion of unsupervised corticosteroid usage is challenging. Apart from evaluating the adrenal function, identifying the concerned drug is the most direct proof of its consumption. While detecting corticosteroids or their metabolites in biological specimens is convincing evidence of their usage, such approach is analytically difficult. More importantly, this approach would not be useful if the patient has stopped taking the drug for some time-a situation that is often encountered clinically. We advocate a more direct approach by measuring corticosteroids in suspicious medicinal products. In the current study, a liquid chromatography-tandem mass spectrometry method for simultaneous detection of 28 corticosteroids in pharmaceutical and proprietary Chinese medicine products was developed and validated for the purpose. The method was applied to 388 cases of suspected unsupervised corticosteroids usage. Among 1,000 products tested, corticosteroids were found in 276 of them and confirmed the clinical suspicion.
Assuntos
Corticosteroides/análise , Preparações Farmacêuticas/química , Espectrometria de Massas em Tandem/métodos , China , Cromatografia Líquida/métodos , Contaminação de Medicamentos , Humanos , Limite de DetecçãoRESUMO
BACKGROUND: Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disease due to impaired decarboxylation of neurotransmitter precursors to its active form. CASE: We retrospectively reviewed 8 cases from 2008 to 2019 with cerebrospinal fluid neurotransmitter analysis performed at our centre. All cases had an elevated urine vanillactic acid and, in most cases, with N-acetylvanilalanine detected. Cerebrospinal fluid analysis showed low downstream metabolites vanillylmandelic acid, homovanillic acid but high 3-O-methyl-L-DOPA, 5-hydroxytryptophan. Cerebrospinal fluid pterins were normal. Genotyping in DDC confirms the diagnosis. Urine organic acid analysis provided the first clue to diagnosis in four of the cases, which then triggered cerebrospinal fluid neurotransmitter and genetic analysis. We also developed a diagnostic decision support system to assist the interpretation of the mass spectrometry data from urine organic acids. CONCLUSIONS: Urine organic acid could be essential in guiding subsequent investigations for the diagnosis of aromatic L-amino acid decarboxylase deficiency. We propose to screen suspected cases first with urine organic acids, specifically looking for vanillactic acid and N-acetylvanilalanine. Suggestive findings should be followed with target analysis for c.714 + 4A > T in ethnically Chinese patients. The assistive tool allowed expedite interpretation of profile data generated from urine organic acids analysis. It may also reduce interpreter's bias when peaks of interest are minor peaks in the spectrum.