Self-limiting COVID-19-associated Kikuchi-Fujimoto disease with heart involvement: case-based review.

BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.

Hepatomegalia, polifagia e hipertransaminasemia / Large liver, polyphagia and hipertransaminasemia

La glucogenosis es una enfermedad metabólica poco frecuente, producida por un trastorno del metabolismo de los hidratos de carbono. Existen múltiples variantes en función de la enzima implicada, la tipo 9 se produce por una deficiencia de la glucógeno desfoforilasa-cinasa a nivel hepático y se caracteriza por la presencia de hepatomegalia, hipertransaminasemia e hipoglucemia con el ayuno. Se presenta el caso de una lactante de 10 meses, cuyos síntomas guías fueron la distensión abdominal y la hiperfagia. El diagnóstico de glucogenosis se confirmó mediante el estudio genético, objetivándose una mutación en el gen PHKG2, compatible con el diagnóstico de enfermedad de almacenamiento de glucógeno tipo 9C. Se instauró tratamiento sintomático, evitando el ayuno y aumentando la ingesta hidratos de carbono de absorción lenta, con buena evolución clínica

Glycogenesis is a rare metabolic disease caused by a carbohydrate metabolism disorder. There are multiple variants depending on the enzyme involved. Type 9 is produced by a deficiency of glycogen defoforilase-kinase in the liver and is characterized by the presence of hepatomegaly, hypertransaminasemia and hypoglycemia during fasting. We describe the case of a 10-month-old girl, whose guiding symptoms were abdominal distention and hyperphagia. The diagnosis of glycogenosis was confirmed by genetic study, observing a mutation in the PHKG2 gene, compatible with the diagnosis of type 9C glycogen storage disease. Symptomatic treatment was established, avoiding fasting and increasing the intake of slowly absorbing carbohydrates, with good clinical evolution

Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis.

In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations (SRSF2/ASXL1/RUNX1 profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

The association of MEFV gene mutations with the disease risk and severity of systemic juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients' severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients. METHODS: The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. RESULTS: The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01-16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models. CONCLUSIONS: The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.

Neurological Involvement in Glycogen Storage Disease Type IXa due to PHKA2 Mutation.

Glycogen storage diseases (GSDs) result from the deficiency of enzymes involved in glycogen synthesis and breakdown into glucose. Mutations in the gene PHKA2 encoding phosphorylase kinase regulatory subunit alpha 2 have been linked to GSD type IXa. We describe a family with two adult brothers with neonatal hepatosplenomegaly and later onset of hearing loss, cognitive impairment, and cerebellar involvement. Whole-exome sequencing was performed on both subjects and revealed a shared hemizygous missense variant (c.A1561G; p.T521A) in exon 15 of PHKA2. The phenotype broadens the clinical and magnetic resonance imaging spectrum of GSD type IXa to include later onset neurological manifestations.

Assessment of remnant liver function and volume after selective ligation of portal vein and hepatic artery in a rat model.

PURPOSE: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. METHODS: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. RESULTS: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. CONCLUSION: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.

Assessment of remnant liver function and volume after selective ligation of portal vein and hepatic artery in a rat model

Abstract Purpose: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. Methods: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. Results: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. Conclusion: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.

Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population.

INTRODUCTION AND OBJECTIVES: Niemann-Pick disease type A (NPD-A) and B (NPD-B) are lysosomal storage diseases with a birth prevalence of 0.4-0.6/100,000. They are caused by a deficiency in acid sphingomyelinase, an enzyme encoded by SMPD1. We analyzed the phenotype and genotype of four unrelated Mexican patients, one with NPD-A and three with NPD-B. PATIENTS AND METHODS: Four female patients between 1 and 7 years of age were diagnosed with NPD-A or NPD-B by hepatosplenomegaly, among other clinical characteristics, and by determining the level of acid sphingomyelinase enzymatic activity and sequencing of the SMPD1 gene. Additionally, a 775bp amplicon of SMPD1 (from 11:6393835_6394609, including exons 5 and 6) was analyzed by capillary sequencing in a control group of 50 unrelated healthy Mexican Mestizos. RESULTS: An infrequent variant (c.1343A>G p.Tyr448Cys) was observed in two patients. One is the first NPD-A homozygous patient reported with this variant and the other a compound heterozygous NPD-B patient with the c.1829_1831delGCC p.Arg610del variant. Another compound heterozygous patient had the c.1547A>G p.His516Arg variant (not previously described in affected individuals) along with the c.1805G>A p.Arg602His variant. A new c.1263+8C>T pathogenic variant was encountered in a homozygous state in a NPD-B patient. Among the healthy control individuals there was a heterozygous carrier for the c.1550A>T (rs142787001) pathogenic variant, but none with the known pathogenic variants in the 11:6393835_6394609 region of SMPD1. CONCLUSIONS: The present study provides further NPD-A or B phenotype-genotype correlations. We detected a heterozygous carrier with a pathogenic variant in 1/50 healthy Mexican mestizos.

Modified Technique of Total Hepatectomy in Polycystic Liver Disease With Caval Flow Preservation: The Exposure Left Lateral Sectionectomy.

BACKGROUND: Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12% to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy to limit hazardous liver manipulation and improve exposure of inferior vena cava in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS). METHODS: From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, which allows for rapid and bloodless transection using electric scalpel. RESULTS: Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 minutes, and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 mL, and no patient required total caval clamping. All patients were alive at the end of the follow-up. CONCLUSIONS: ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation.

Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents.

BACKGROUND: Chanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by ichthyosiform non-bullous erythroderma and variable involvement of the liver and the neuromuscular system. In CDS patients, the accumulation of neutral lipids inside cytoplasmic lipid droplets has been demonstrated in different tissues. To date, ninety families with this disease have been described worldwide; most of them are from Mediterranean countries. CASE PRESENTATION: In this report, we describe a consanguineous Turkish family with typical features of CDS. The parents are first cousins and are both diseased. At the age of eight, their child presented CDS with non-bullous congenital ichthyosiform erythroderma, hepatosteatosis, hepatomegaly and ectropion. Electromyographic examination is compatible with myopathy. A five-year-old cousin of the child is also affected by CDS. She was born to non-affected consanguineous parents. Mutation analysis of the ABHD5 gene revealed the previously reported mutation, N209X, which is the most frequent in Turkish patients. Lipid vacuoles, also known as Jordan's anomaly, are detectable in their leucocytes. CONCLUSIONS: To the best of our knowledge, this is the first report of a CDS family in which both parents and their child are affected by CDS. To date, the child does not present a more severe clinical phenotype compared with those of his relatives or other CDS patients of the same age. These findings suggest that high levels of triacylglycerol accumulation, that may be supposed to be present in high amount inside the ooplasm, did not affect embryo development and foetal growth.

Paediatric fatty liver disease (PeFLD): All is not NAFLD - Pathophysiological insights and approach to management.

The recognition of a pattern of steatotic liver injury where histology mimicked alcoholic liver disease, but alcohol consumption was denied, led to the identification of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease has since become the most common chronic liver disease in adults owing to the global epidemic of obesity. However, in paediatrics, the term NAFLD seems incongruous: alcohol consumption is largely not a factor and inherited metabolic disorders can mimic or co-exist with a diagnosis of NAFLD. The term paediatric fatty liver disease may be more appropriate. In this article, we summarise the known causes of steatosis in children according to their typical, clinical presentation: i) acute liver failure; ii) neonatal or infantile jaundice; iii) hepatomegaly, splenomegaly or hepatosplenomegaly; iv) developmental delay/psychomotor retardation and perhaps most commonly; v) the asymptomatic child with incidental discovery of abnormal liver enzymes. We offer this model as a means to provide pathophysiological insights and an approach to management of the ever more complex subject of fatty liver.

Clinicohematological Study of Pancytopenia in a Tertiary Care Hospital of Western Region of Nepal.

INTRODUCTION: Pancytopenia is a relatively common hematological entity and is a manifestation of many illnesses which can be life threatening at times. The severity of pancytopenia and the underlying pathology determine the management and prognosis. This study was conducted to evaluate hematological and bone marrow findings in patients presenting with pancytopenia. METHODS: A prospective observational study was conducted in Department of Pathology, Manipal College of Medical Sciences, Pokhara from January 2011 to December 2016. Clinical and hematological parameters including bone marrow aspiration and biopsy were evaluated in all patients who presented with pancytopenia. RESULTS: Among 138 cases studied, patients' age ranged from 2 to 82 years with a mean age of 43.95 years, and there was male predominance. Most of the patients presented with generalized weakness, pallor, dypnoea and fever. Hypoplastic marrow was seen in 38 (27.5%) cases, followed by 26 (18.8%) cases of megaloblastic anemia and 19 (13.76%) cases of acute leukemia. Other findings included one case each of hemophagocyosis, leishmaniasis, plasmodium vivex malaria and metastatic carcinoma. CONCLUSIONS: This study highlights that pancytopenia is a common hematological problem and that the study of detailed primary hematological investigations along with bone marrow study in patients with pancytopenia will help to identify the cause for further planning and management.

Gastrointestinal system manifestations in juvenile systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%). The GIS manifestations due to SLE were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). Manifestations associated with SLE were hepatomegaly and hypertransaminasemia due to macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one, methotrexate in another, and azathioprine in another patient), azathioprine-induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a coincidence. In this study, one of every five pediatric SLE patients had GIS-related manifestations. GIS involvement may occur as an initial manifestation of the disease.

Serial cardiac MRIs in adult Fontan patients detect progressive hepatic enlargement and congestion.

BACKGROUND: The progression of hepatic disease in adult Fontan patients is not well understood. They reviewed the experience with serial cardiac MRIs (CMR) in adult Fontan patients to determine if hepatic anatomic markers of prolonged Fontan exposure were present and if clinical predictors of progressive hepatic congestion could be identified. METHODS AND RESULTS: A retrospective cohort study of all adult Fontan patients who had undergone at least two CMRs was performed. Hepatic dimensions, inferior vena cava (IVC) size, right hepatic vein (RHV) size and spleen diameter were determined from images acquired at the time of clinically guided CMR. Two radiologists with expertise in hepatic imaging graded congestion and liver size independently using post-gadolinium contrast sequences. Twenty-seven patients met inclusion criteria. Over a mean time of 5.1 years between CMRs, there was a significant increase in mean lateral-medial hepatic dimension (P = .005), mean RHV diameter (P = .004), and mean splenic diameter (P = .001). Serial post-gadolinium imaging was available in 25/27 (93%) patients of which 15/27 (55%) showed evidence of progressive hepatic congestion across serial studies. Progressive hepatic congestion was associated with single ventricle ejection fraction (SVEF) less than 50% (P = .008), and larger indexed end-diastolic (EDVI) and end-systolic volume (ESVI). RHV diameter was the only anatomic variable significantly correlated with time from Fontan completion (P = .004). CONCLUSIONS: Serial CMRs detected progressive liver and hepatic vein enlargement in our cohort of adult Fontan patients over a mean time of 5.2 years. Progressive hepatic congestion occurs in a significant number of adult Fontan patients and may be associated with ventricular enlargement and decreased ventricular function by CMR.

Idiopathic myelofibrosis with disseminated hepatosplenic, mesenteric, renal and pulmonary extramedullary haematopoeisis, portal hypertension and tuberculosis: initial presentation and 2†years follow-up.

A 35-year-old man with a 12-year history of idiopathic myelofibrosis (IMF) presented in 2014 with fatigue and abdominal distension. CT scan revealed massive hepatosplenomegaly with focal splenic lesions, soft tissue around renal pelvis, mesenteric masses compressing bowel loops and perilymphatic nodules in lungs. There was portal hypertension, ascites, pleural effusion, bilateral psoas abscesses and necrotic retroperitoneal lymphadenopathy. MRI additionally revealed hypointense periportal infiltrative lesions in liver, not seen on CT scan. None of these lesions showed diffusion restriction. Biopsy from mesenteric masses revealed extramedullary haematopoeisis. Aspiration from psoas abscess confirmed tuberculosis. Follow-up after 6 weeks of ruxolitinib (JAK2 tyrosine kinase inhibitor) and 9 months of antitubercular therapy revealed resolution of psoas abscesses and lymph nodes. Mild reduction was noted in mesenteric masses and ascites while perirenal soft tissue had increased. Follow-up imaging after another 1 year of ruloxitinib showed new-onset bilateral paravertebral and presacral foci of extramedullary haematopoeisis.

Usefulness of the Sum of Pulmonary Capillary Wedge Pressure and Right Atrial Pressure as a Congestion Index that Prognosticates Heart Failure Survival (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial).

In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, use of a pulmonary artery catheter did not significantly affect advanced heart failure outcomes. However, the success of achieving the targeted hemodynamic goals of pulmonary capillary wedge pressure (PCWP) of 15 mm Hg and right atrial pressure (RAP) of 8 mm Hg and the association of these goals with clinical outcomes were not addressed. Furthermore, goals with 2 independent variables, PCWP and RAP, left room for uncertainties. We assessed the ability of a single hemodynamic target to achieve a threshold sum of PCWP and RAP as a predictor of all-cause mortality, death-or-transplantation (DT), or death-or-rehospitalization (DR) at 6 months in the pulmonary artery catheter-guided treatment arm of ESCAPE (n = 206). Patients with a posttreatment PCWP + RAP of <30 mm Hg had characteristics similar to those of the population who achieved the ESCAPE hemodynamic goals. This group had 8.7% mortality, 13.0% DT, and 58.7% DR at 6 months. The contrasting cohort with PCWP + RAP of ≥30 mm Hg had 45.3% mortality, 54.7% DT, and 84.9% DR at 6 months, with greater relative risk (RR) of death (RR 5.76), DT (RR 4.92), and DR (RR 1.80) and higher prevalence of jugular venous pulsation, edema, hepatomegaly, and ascites at admission and discharge. In conclusion, PCWP + RAP of 30 mm Hg posttreatment, obtained early in the index hospitalization, may represent as a simple congestion index that has prognostic value for heart failure survival and readmission rates at 6 months and as a warning signal for more aggressive intervention, thus warranting further validation.

Seven novel mutations of the SMPD1 gene in four Chinese patients with Niemann-Pick disease type A and prenatal diagnosis for four fetuses.

BACKGROUND: Niemann-Pick disease type A (NPD-A) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency. Only a few cases have been documented in mainland China, and prenatal diagnosis has not been performed to date. In this study, the clinical and laboratory features of four Chinese patients with early-onset NPD-A were summarized. METHODS: Four patients with NPD-A were the firstborns of non-consanguineous parents from four unrelated Chinese families. Bone marrow analysis, acid sphingomyelinase assay and genetic studies were performed. SMPD1 gene studies on amniocytes were performed for the prenatal diagnosis of four fetuses from three families. RESULTS: Four patients were admitted at the age of 1-10 months due to jaundice, hepatosplenomegaly and psychomotor retardation. Liver histopathological analysis revealed glucolipid accumulation. Massive foamy histiocytes were found in the bone marrow. Acid sphingomyelinase activities of peripheral blood leukocytes were significantly decreased (4.05-21.9 nmol/h/mg protein, normal range 216.1-950.9 nmol/h/mg protein). Seven novel mutations (c.518-519insT, c.562_563insC, c.792Gdel, c.949G>A, c.1487_1499delACCGTGTGTACCA, c.1495T>C and c.1670T>C) of the SMPD1 gene were identified in four patients. Only one fetus had two mutations of the SMPD1 gene of amniocytes. The results suggested that the fetus was affected by NPD-A. The mother chose artificial abortion. The other three fetuses were not affected by NPD-A. No mutation of the SMPD1 gene was detected in the cultured amniocytes from the mothers. Postnatal genetic analysis and normal development of the three infants confirmed the prenatal diagnosis. CONCLUSIONS: Seven novel mutations associated with NPD-A were identified in the Chinese population. Prenatal diagnosis for four fetuses of three families was successfully performed by amniocyte gene analysis.

Hepatic inflammatory biomarkers and its link with obesity and chronic diseases / Biomarcadores hepáticos de inflamación y su vínculo con la obesidad y las enfermedades crónicas

Introduction: The low-grade inflammation and insulin resistance are two events that could be present in varying degrees, on obesity and chronic diseases. The degree of subclinical inflammation can be gauged by measuring the concentrations of some inflammatory biomarkers, including the hepatic origin ones. Some of those biomarkers are sialic acid, alfa1 -antitrypsin and the C-terminal fragment of alpha1-antitrypsin, ceruloplasmin, fibrinogen, haptoglobin, homocystein and plasminogen activator inhibitor-1. Objectives: To approach the relation between adiposity and hepatic inflammatory markers, and to assess the possible associations between hepatic inflammatory biomarkers and obesity, as well as their capacity of predicting chronic diseases such as type 2 diabetes and atherotrombotic cardiovascular diseases. Methods: We used electronic scientific databases to select articles without restricting publication year. Results: The sialic acid predicts the chance increase to become type2 diabetic independently of BMI. Moreover, the alfa1 -antitripsin, ceruloplasmin, fibrinogen and haptoglobulin biomarkers, seem predict the chance increase to become type2 diabetic, dependently, of BMI. So, this process could be aggravated by obesity. The concentrations of fibrinogen, homocystein and PAI-1 increase proportionally to insulin resistance, showing its relation with metabolic syndrome (insulin resistance state) and with type2 diabetes. In relation to cardiovascular diseases, every biomarkers reported in this review seem to increase the risk, becoming useful in add important prognostic. Conclusion: This review integrates the knowledge concerning the possible interactions of inflammatory mediators, in isolation or in conjunction, with obesity and chronic diseases, since these biomarkers play different functions and follow diverse biochemical routes in human body metabolism (AU)

Introdución: El bajo grado de inflamación y la resistencia a la insulina son dos eventos que podrían estar presentes en mayor o menor grado, en la obesidad y las enfermedades crónicas. El grado de inflamación subclínica se puede evaluar por medición de las concentraciones de algunos biomarcadores inflamatorios, incluyendo los de origen hepático. Algunos de estos biomarcadores son el ácido siálico, α1-antitripsina y el fragmento C-terminal de la alfa 1 antitripsina, ceruloplasmina, fibrinógeno, haptoglobina, la homocisteína y el inhibidor-1 del activador del plasminógeno. Objetivos: Evaluar la relación entre la obesidad y los marcadores de inflamación hepática, y las posibles asociaciones entre los biomarcadores inflamatorios hepáticos y la obesidad, así como su capacidad de predicción de las enfermedades crónicas como la diabetes tipo 2 y enfermedades cardiovasculares aterotromboticas. Métodos: Se utilizaron bases científicas electrónicas para selección de artículos, sin límite de año de publicación. Resultados: El ácido siálico predice el aumento de convertirse en diabéticos tipo 2 independientemente del IMC. Por otra parte, los biomarcadores α1-antitripsina, ceruloplasmina, fibrinógeno y haptoglobulina, parecen predecir el aumento de convertirse en diabético tipo 2, dependiente, de IMC. Por lo tanto, este proceso podría verse agravada por la obesidad. Las concentraciones de fibrinógeno, homocisteína y PAI-1 incrementan proporcionalmente a la insulinoresisténcia, mostrando su relación con el síndrome metabólico (estado de resistencia insulínica) y con la diabetes tipo 2. En relación con las enfermedades cardiovasculares, cada biomarcador informado en esta revisión parece aumentar el riesgo, llegando a ser muy útil en el complemento pronóstico. Conclusion: Esta revisión se integra el conocimiento acerca de las posibles interacciones de los mediadores inflamatorios, en forma aislada o en combinación, con la obesidad y las enfermedades crónicas, ya que estos biomarcadores desempeñan funciones diferentes y siguen diversas rutas bioquímicas en el metabolismo del cuerpo humano (AU)

Capillary bedside blood glucose measurement in neonates: missing a diagnosis of galactosemia.

A number of factors may lead to inaccuracy in measurement of capillary blood glucose with a glucometer. Measurement of other carbohydrate molecules such as galactose and fructose along with glucose can potentially be a cause of error. We report a newborn patient who was referred to our hospital with conjugated bilirubinemia, hepatomegaly and high capillary blood glucose levels measured with a glucometer. Simultaneous biochemical measurements revealed normal blood glucose levels. Further investigation led to a diagnosis of classical galactosemia. Capillary blood glucose level measured with glucometer also dropped to normal values following cessation of breastfeeding and initiation of feeding with a lactose-free formula.