Homozygous familial hypobetalipoproteinemia caused by APOB gene variations: a case report and review of literature / 中华儿科杂志

Objective: To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. Methods: The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children's Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with "familial hypobetalipoproteinemia" or "hypobetalipoproteinemias" or "hypo beta lipoproteinemia" or "hypolipoproteinemias" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. Results: The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. Conclusions: The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.

Consideraciones clínicas de la abetalipoproteinemia: revisión de la literatura / Clinical considerations of abetalipoproteinemia: literature review

La abetalipoproteinemia es una enfermedad rara que se suele presentarse en la primera década de la vida; sus principales manifestaciones son esteatorrea, alteración en el desarrollo y niveles plasmáticos lipídicos onsiderablemente disminuidos. Sin embargo, este cuadro suele ser confuso, puesto que existe un grupo de desórdenes genéticos que conllevan a mala absorción lipídica, que requieren un exhaustivo diagnóstico diferencial desde el punto de vista clínico, bioquímico y molecular. Este artículo expone una revisión actualizada sobre la abetalipoproteinemia, enfocándose en su fisiopatología, manifestaciones sistémicas, diagnóstico y abordaje en general, para facilitar su comprensión integral. La estrategia de búsqueda y los métodos de selección de estudios se realizó con base en elementos de la declaración prisma y guías Cochrane, utilizando términos de búsqueda tales como "abetalipoproteinemia" ,"bioquímica" y sinónimos, los cuales fueron combinados con los operadores "and" y "or", en las bases de datos PubMed, Science Direct, Clinical Key y Ebsco. No existe mucha literatura específica sobre esta condición, lo cual explica que sea una entidad subvalorada y poco conocida. Es fundamental realizar más investigaciones en torno al tema, pues en caso de no establecerse un diagnóstico y manejo adecuado, las complicaciones serán muchas y severas..Au

Abetalipoproteinemia is a rare disease that occurs predominantly in the first decade of life, having as main manifestations, steatorrhea, alteration in development and considerably decreased lipid plasma levels. However, this clinical presentation is often confusing, since there is a group of genetic disorders that lead to poor lipid absorption, requiring the need to make a comprehensive differential diagnosis from a clinical, biochemical and molecular point of view. This article will provide an updated review on Abetalipoproteinemia, focusing on its pathophysiology, systemic manifestations, diagnosis and general approach, allowing easy access to an integral knowledge. The search strategy and study selection methods were based on elements of the prisma statement and Cochrane guidelines, using search terms such as "Abetalipoproteinemia" and "Biochemistry", in addition to synonyms, which were combined with "and" and "or" operators, in the PubMed, Science Direct, Clinical Key and Ebsco databases. It is necessary to highlight that there is not much specific literature on this condition, which would support the fact that it is an undervalued and little-known entity, it is essential to carry out more research on the subject, taking into account that if a diagnosis is not established proper management, the complications are many and severe..Au

The First Genetically Confirmed McLeod Syndrome in Korea

McLeod syndrome is a rare X-linked multisystem disorder which forms the core of neuroacanthocytosis syndrome. Neurological symptoms characterized by chorea, seizure, cognitive impairment, and psychosis mostly develop around the 5-6th decades, accompanied by multisystem involvement comprising neuropathy, myopathy, acanthocytosis and hepatosplenomegaly. We hereby present a 60-year-old male who is the first genetically confirmed Korean McLeod syndrome patient. Genetic analysis of his XK gene revealed a previously reported 5 base pair deletion of exon 3 (c.856_860delCTCTA).

Hipobetalipoproteinemia primária: relato de caso / Primary Hypobetalipoproteinemia: a case report

Descrevemos o caso de uma paciente de 19 anos diagnosticada com hipobetalipoproteinemia primária. A paciente apresentava sintomas compatíveis com a doença como diarreia desde o primeiro mês de vida, défice de crescimento e retinopatia. A biópsia duodenal evidenciou presença de vacúolos lipídicos intraepiteliais, os quais foram altamente sugestivos para o diagnóstico. Os exames complementares evidenciaram disfunção hepática, baixos níveis séricos de triglicerídeos, e de colesterol total e frações. Após a dosagem de apolipoproteína B abaixo dos valores da normalidade, aliada a clínica e exames complementares, o diagnóstico foi realizado. A relativa escassez de dados na literatura em nosso meio, atrelada à raridade da doença, ilustra a relevância deste relato de caso, somado à importância do diagnóstico precoce

The case of a 19-year-old female patient who was diagnosed with Primary Hypobetalipoproteinemia (HBL) is described.The patient presented symptoms that were consistent with the disease, such as diarrhea from the very first month of life, growth failure and retinopathy. The duodenal biopsy showed the presence of intraepithelial lipid vacuoles that were highly suggestive of the diagnosis. Further tests showed liver dysfunction, low serum levels of triglycerides and total cholesterol and fractions. After the dosage of Apolipoprotein B below normal values, and clinical exam along with laboratory tests, the diagnosis was made. The lack of data in the literature and the rarity of the disease illustrate the importance of this case report,and of an early diagnosis.

La ciencia médica versus creencia en dios: La conservación del mito / Medical science versus belief in god: Myth conservation

Objetivo: plantear una serie de reflexiones sobre la enseñanza de la Medicina con base en la ciencia médica versus la enseñanza con base en el dogma por creencia de un dios. Discusión: Se argumenta la adquisición de apoyos sólidos y reales tomados de la demostración que se logra con la ciencia médica, para que los diversos profesionales de la salud y sus pacientes crean en sus logros, acercándolos más a los beneficios que brinda la aplicación de la ciencia en el campo médico, desligándose de la aceptación del dogma religioso que evita la reflexión y el análisis inteligente sobre los eventos que relacionan los procesos de salud y enfermedad. Conclusión: Aunque se ha avanzado mucho en el campo medico;su aplicación científica,para tratar de mejorar la salud del paciente, aún se conserva la mítica creencia de una deidad que rige el mundo y que a su vez desliga al médico de dicho logro.

Globus Pallidus Interna Deep Brain Stimulation for Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis. Pharmacotherapy for control of involuntary movements has generally been of limited benefit. Deep brain stimulation (DBS) has recently been used for treatment of some refractory cases of ChAc. We report here on the effect of bilateral high-frequency DBS of globus pallidus interna in a patient with ChAc.

Acanthocytosis in a Patient with Chorea-acanthocytosis

No abstract available.

Acanthocytosis in a Patient with Chorea-acanthocytosis

No abstract available.

Treatment of Psychiatric Symptoms in a Patient with Neuroacanthocytosis: A Case Report / 대한정신약물학회지

Neuroacanthocytosis is a rare hereditary disorder characterized by various neurological symptoms and the presence of abnormal red blood cell called acanthocytosis. Degeneration of striatum, which accounts for characteristic motor and psychiatric symptoms, mainly attributes to the pathology of neuroacanthocytosis. We experienced a case of chorea-acanthocytosis. He was a 50 year-old-man who presented with orofacial dyskinesia, dysarthria, uncontrolled lip biting, generalized choreic movements and sensorymotor polyneuropathy. He was also suffered from obsessive eating behavior, disinhibition, impulsivity and sleep disturbance. After antipsychotic medication, his psychiatric problems were improved. Clinicians must consider psychiatric managements of progressive neurological disorder for patients' quality of life and reducing their caregiver's burden.

O relato de caso como situação gnosiológica: reflexões sobre a prática diagnóstica em patologia a partir de um caso de abetalipoproteinemia / The case report as a gnosiological situation: reflections on diagnostic pathology, based on a case of abetalipoproteinemia

Neste ensaio, aproveita-se um caso raro de abetalipoproteinemia, diagnosticado a partir dos achados anatomopatológicos de biópsia jejunal, para refletir sobre a prática diagnóstica em patologia. Mais do que narrar o caso e comentar seu conteúdo, como usualmente se faz nos relatos de caso, o caso, como objeto de estudo, pode ser empregado como matéria para reflexão sobre a prática. O caso é objeto mediatizador da reflexão que se faz sobre a prática, possibilitando um desvelamento da realidade, na qual se insere o exercício da medicina.

This article draws on a rare case of abetalipoproteinemia, diagnosed from the pathological findings of a jejunal biopsy, as the point of departure for reflecting on practice in diagnostic pathology. Rather than present a case and comment on its content, as usually happens in case reports, the case, as object of study, can be used as material for reflection on practice. The case is the mediating object of reflection on the practice, allowing an unveiling of reality in which medical practice is a part.

Evaluación de las concentraciones de lípidos y apoproteínas A-I y B-100 en un grupo de escolares de cinco departamentos del centro-oriente de Colombia / Lipid and apoprotein A-I and B-100 levels in school children school from five centraleastern provinces of Colombia

Introducción. Existe evidencia sobre variaciones en las concentraciones de lípidos y apoproteínas en los niños asociados a cambios fisiológicos o al medio ambiente, este último puede inducir alteraciones futuras en los lípidos. Objetivo. Evaluar las concentraciones de colesterol total, colesterol LDL, colesterol HDL y apoproteínas A-1 y B-100 en escolares de cinco departamentos del centro-oriente colombiano, y comparar por edad, sexo, índice de masa corporal, práctica de actividad física y preferencias hacia algunos alimentos. Materiales y métodos Se recolectaron 741 muestras de sangre que se analizaron por métodos enzimáticos, colorimétricos e inmunoturbidimétricos. Todos los valores se presentaron como media y desviación estándar y para la comparación entre grupos se utilizó prueba t, ANOVA y Scheffe. Resultados. Se observaron variaciones en los lípidos y valores constantes en las apolipoproteínas, las concentraciones de los lípidos se relacionaron con los cambios de edad y sexo. Se observaron cambios que pueden asociarse al grado de maduración sexual, dieta y nivel de actividad física. Los valores de colesterol total, colesterol LDL y colesterol HDL fueron más bajos a los reportados en otros grupos de población mientras que en los triglicéridos hay mayor variación con tendencia a ser superiores. Conclusión. Existen otras variables diferentes a la edad y el género que influyen en las variaciones de los lípidos; se requieren otros estudios para determinar la contribución de cada factor. La promoción de estilos de vida saludable puede ayudar a disminuir el riesgo futuro de enfermedad cardiovascular asociada a bajas concentraciones de colesterol HDL y mayores de triglicéridos en esta población.

Introduction. Lipid and apolipoprotein are known to vary in children.These variations can be associated to physiologic changes or the environment; this last one probably induces future alterations in the lipids. Objetive. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and apoproteins AI and B-100 were compared in school children from five provinces of middle-eastern Colombia. Associations were made with age, gender, body mass index, fitness activity, and food preference. Materials and methods. 741 blood samples were collected and biochemical determinations were undertaken with standard enzymatic, colorimetric, and inmunoturbidimetric methods. All values are presented as mean ± SE, comparisons among groups were made using Student´s t test, ANOVA and Scheffe. Results. Lipid variation was observed in the school children, however in contrast, the concentrations of Apoproteins ApoB-100 and ApoA-I tended to be constant. The lipid fluctuations showed some relationship with changes in age and gender, however, changes were also observed that indicate a possible relationship with sexual maturation, diet and fitness activity. An important finding was that the HDL cholesterol value was lower that reported from other countries, while the triglycerides was higher and this may indicate a future increased risk for cardiovascular diseases. Conclusion. Fluctuations occur in the lipid levels and vary with age and gender. Associations with other factors may be present; however, more research is necessary to determinate the contribution of each factor. A promotion campaign among school-age children for a healthier life style may contribute to a decrease in future risk for cardiovascular diseases associated with low HDL-cholesterol levels and higher triglycerides.

Correlación entre las concentraciones séricas de apolipoproteína B y colesterol LDL en una muestra poblacional. Utilidad de la apolipoproteina B para valorar riesgo aterogénico / Correlation between serum concentrations of apolipoprotein B and LDL cholesterol in a population sample. Usefulness of apolipoprotein B to value atherogenic risk

La apolipoproteina B (apoLp B) es el principal constituyente proteico de la vía aferente del colesterol a los tejidos periférico. Se ha propuesto que sea un mejor marcador de enfermedad cardiovascular que el colesterol LDL(cLDL). El objetivo de este trabajo es determinar las concentraciones plasmáticas de apoLp B, su relación con el cLDL, el valor deseable y de alto riesgo, y evaluar las hiperapolipoproteinemias B en pacientes con cLDL por debajo del valor de riesgo (cLDL<160 mg/dl). Se estudiaron 265 muestras de pacientes en el Hospital Universitario. Se determinó apolipoproteina B, CT, TG, cHDL y cálculo de cLDL. Cuando el valor de cLDL fue < 130 mg/dl, el valor de apoLp B fue < 98 mg/dl, un valor deseable. Para un valor de cLDL > 160 mg/dl, el valor de apoLp B fue > 120 mg/dl, un valor de riesgo alto. De los pacientes con cLDL<160 mg/dl (n=202), un 3,5% tuvieron valores de apoLp B mayores de 120 mg/dl. Encontramos un valor deseable de apoLp B de 98 mg/dl y un valor de riesgo alto de 120 mg/dl. Un 3,5% de pacientes que teniendo valores de cLDL de 160 mg/dl presentaron apolipoproteina B>120 mg/dl, que podría corresponder a pacientes con hiperapolipoproteinemia B. Es en estos pacientes con sospecha de alto riesgo coronario pero que presentan cLDL por debajo del nivel de riesgo, en quienes se recomienda dosificar apoLp B, como factor emergente de riesgo coronario.

Apolipoprotein B (apoLp B) is the main protein component of the cholesterol delivery route to peripheral tissues. It has been proposed as a better predictor of cardiovascular disease than LDL cholesterol. The aims of this study were to determine the serum concentration of apoLp B, its relation with LDL cholesterol, its "desirable" and "high risk" limits and to evaluate patients with hyperapolipoproteinemia B and cLDL below risk values. A total of 265 subjects were randomly selected from a population referred for lipid studies to the Hospital Universitario. We measured concentrations of apoLp B, total cholesterol, triglycerides, HDL cholesterol and calculated LDL cholesterol. When LDL cholesterol was < 130 mg/dl, apoLp B value was < 98 mg/dl, which corresponds to a "desirable" limit. When LDL cholesterol was >160 mg/dl, apoLp B value was > 120 mg/dl, corresponding to a "high risk" limit. Of all patients with LDL cholesterol < 160 mg/dl (n=202), 3.5% had apolipoprotein B > 120 mg/dl. We found a desirable apoLp B value of 98 mg/dl and high risk apoLp B value of 120 mg/dl. In the patients with LDL cholesterol below 160 mg/dl, 3.5% showed apoLp B values above 120 mg/dl and they were considered patients with hyperapolipoproteinemia B. In this population with suspicion of coronary disease but without risk LDL cholesterol values, the measurement of apoLp B, as an emerging coronary risk factor, is strongly recommended.

Abetalipoproteinemia: monitoreo del tratamiento / Abetalipoproteinemia: monitoring of therapy

La abetalipoproteinemia es causada por un defecto en la síntesis de β-lipoproteínas plasmáticas, VLDL y quilomicrones. Cursa con desnutrición grave, diarrea crónica mal absortiva, polineuritis, ataxia, retinitis pigmentaria y acantocitosis. Se presenta un niño de cinco años de edad que consultó por un cuadro compatible con esta enfermedad. El diagnóstico se hizo por biopsia de intestino delgado y laboratorio. Se inició tratamiento con dieta hipograsa y triglicéridos de cadena mediana, formas hidrosolubles de vitaminas A y D, altas dosis de vitaminas E y K intramuscular y lípidos endovenosos en forma periódica para la provisión de ácidos grasos esenciales ante evidencias de deficiencia. Recibió lípidos endovenosos quincenalmente durante cinco años hasta que comenzó con reacciones de intolerancia durante las infusiones, que hubo que espaciar. La recuperación fue excelente. Hoy, a los catorceaños, es un adolescente normal, con desarrollo y tamaño corporal normales para su edad. Ante la imposibilidad de monitorear el estado nutricional (deficiencia o exceso) en ácidos grasos esenciales y vitaminas, eventualidad posible por lo atípico de la dieta, el síndrome mal absortivo y debido a los valores no dosables en plasma se obtuvieron tres biopsias de tejido adiposo. Los resultados demostraron la dependencia de las infusiones y una composición diferente del tejido adiposo, según los distintos momentos del tratamiento y en comparación con la de los adultos normales de nuestro país. Consideramos que la determinación de ácidos grasos en el tejido adiposo es una herramienta útil en el monitoreo del tratamiento de esta grave enfermedad.

Importance of screening the peripheral smear.

A 5-year-old boy presented with history of failure to thrive from infancy. There was a history of one sibling death due to similar problems and history of severe abortions in the mother. Routine examination of peripheral smear revealed more than 50% acanthocytes. Based on this tests were streamlined to doing lipid profile and Lipo protein electrophoresis which revealed hypolipidemia and absent beta hypo protein band. Jejunal mucosal biopsy confirmed the diagnosis of A Beta Lipo proteinemia which revealed lipid laden enterocytes. This case illustrates the importance of simple tests like peripheral smear examination in streamlining further tests in the diagnosis of major diseases.

Relación entre apolipoproteínas A-1 y B-100 e infarto al miocardio / Relation between apolipoproteins A-1 and B-100 e infarction myocardial

La enfermedad ateroesclerótica (EA) es la primera causa de muerte en Venezuela, determinándose marcadores más específicos para EA, en 47 sobrevivientes al infarto de miocardio y 40 controles (sexo masculino, 30-60 años). Indicadores: apolipoproteínas (Apo) A-1 y B-100, Colesterol total (Ct), HDLc, LDLc, Vldlc, triglicéridos y sus relaciones. Diferencias estadísticamente significativas: Apo A-1, Ct/HDLc y LDLc/HDLc (p<0.0005); B-100 y LDLc (p<0.05); HDLc (p<0.025); Apo A-1/Apo B-100, LDLc/Apo A-1 y Ct/Apo A-1 (p>0.0001). Apo A-1 [CD=68 por ciento; Vp(+)=71], Apo A-1/Apo B-100 [CD=75 por ciento, Vp(+)=75 por ciento], LDLc/Apo A-1 [CD=66 por ciento, Vp(+)=71 por ciento] y Ct/Apo A-1 [CD=70 por ciento, Vp(+)=71 por ciento] constituyeron marcadores de riesgo más especifícos para EA que el perfil lipídico y que las relaciones utilizadas actualmente [Ct/HDLc: CD=66 por ciento, Vp(+)=67 por ciento, LDLc/HDLc: CD=65 por ciento, Vp(+)=67 por ciento]

Neurological Aspects of the Patient with Spasmodic Dysphonia

Spasmodic dysphonia Is a form of focal dystonia affecting laryngeal muscles. There have been a few reports on the neurological aspects of the patient with spasmodic dysphonia. No data on the clinical courses and possible causative neurological diseases have been reported. We analysed 44 patients with spasmodic dysphonia, using a check-list of clinical symptoms and laboratory tests in a prospective manner, Forty one patients had adductor type of spasmodic dysphonia and three patients had abductor type. Five different clinical courses have been identified ; about half of the patients showed relentless progress of symptoms for many years(range 1-26 years ; mean 9.8 years). Magnetic resonance imaging study of the brain showed abnormalities in three patients(2 had a focal lesion in the basal ganglia and 1 had multiple cerebral infarctions). One showed acanthocytosis on electron-microscopic examination of the peripheral blood smear. Navicular tremor, low facial dyskinesla, and development of other involuntary movement at the time of onset of spasmodic dysphonia may be clues suggestive of symptomatic form of spasmodic dysphonia.

A Familial Case of Choreoacanthocytosis

We have experienced a family case of 3 sisters in whom the proband showed a complete form of the choreo-acanthosytosis. 439-year-old female proband was admitted because of frequent seizures. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements of chin. Deep tendon reflexes on the both lower extremities were decreased. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, increased creatine-phosphokinase levels and bilateral caudate atrophy on her brain CT scan. Electrophysiological data were consistent with lower motor neuron dysfunction. Another 33-year-old sister with frequent seizures and psychic problems also showed acanthocytosis. The other 36-year-old sister has been treated under the diagnosis of schizophrenia for 10 years, not showing acanthocytosis.

Neuroacanthocytosis: 2 Cases of Familial Choreoacanthocytosis

Neuroacanthocytosis is a rare dosorder characterized by various neurological manifestations and the presence of abnormal red blood cells called acanthocytes which have a disturbed morphology showing spiky, knobby end projections. Acanthocytosis associated with neurological involvements includes 3 major syndromes ; Bassen-Korzweig syndrome, choreoacanthocytosis (or Levine-Critchley syndrome), and Mcleod syndrome. Here, we report two cases of familial choreoacanthocytosis. A 40 years old man presented with orofacial dyskinesia, involuntary vocalization, dysarthria, dysphagia, generalized choreic movements, hyporef lexia, and amyotrophy of the bilarteral anterior tibilais muscles. Serum creatine phosphokinase was increased. Scanning electronmicroscopic examination of the fresh peripheral blood smear film showed acanthocytes, corresponding to about 6% of all red blood cells. His one of two daughter had high arched foot, bradykinesia, and hypoactive deep tendon reflexes. A 70 years old woman showed head and hand tremor, bilateral eye brow choreic movements, torticollis and bradykinesia. Her mother and two younger sisters had head termor. Serum creatine phosphokinase level was normal. Scanning electronmicroscopic examination of the fresh peripheral blood smear showed acnthocytes, corresponding to 9% of the examined red blood cells.