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Objectives: This study examines the clinical-pathological profiles of patients with glycogenic hepatopathy in a contemporary cohort of patients at an adult acute care hospital., Methods: Liver biopsies with glycogenic hepatopathy were retrieved from the departmental surgical pathology database, the histological findings were studied, and the clinical findings were reviewed., Results: Five cases of glycogenic hepatopathy were found, including cases associated with type 1 diabetes mellitus (n = 1), type 2 diabetes mellitus (n = 1), corticosteroids (n = 2), and anorexia (n = 2, including the patient with type 1 diabetes). AST and ALT were normal to mildly elevated (13-115 U/L and 7-126 U/L, respectively). Trace ascites was present in two patients. Hepatomegaly was only present in the patient with type 1 diabetes at the time of diagnosis., Conclusions: Four of five cases were associated with etiologies other than type 1 diabetes, which is widely reported as the most common etiology of glycogenic hepatopathy. This study suggests that etiologies currently only rarely recognized may actually be more common causes of glycogenic hepatopathy than type 1 diabetes in a contemporary adult population. It is important not only to recognize that these rarely reported causes of glycogenic hepatopathy may be underrecognized, but that the clinical presentation may also be mild., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: Amyloidosis is a systemic disease characterized by extracellular deposition of amyloid protein, most commonly in the heart and kidney. Hepatic amyloidosis is a rare form of presentation that ranges from mild hepatomegaly and altered liver biochemical tests to acute liver failure. The aims of this study were to evaluate the prevalence of amyloidosis in patients undergoing liver biopsy and describe its main clinical characteristics and prognostic impact., Methods: A retrospective analysis of all patients with a histological diagnosis of hepatic amyloidosis between January 2010 and December 2019 was performed., Major Results: A total of 7 patients were identified from a total of 1773 liver biopsy procedures (0.4%), with a female predominance (6/7) and median age of diagnosis of 62 years. The most common clinical manifestations included hepatomegaly (4/7), jaundice (2/7) and peripheral edema (2/7), whereas 3/7 patients were asymptomatic. Every patient presented abnormalities in liver biochemical tests, more commonly cholestasis (6/7), but also cytolysis (4/7) or hyperbilirubinemia (2/7). Abnormal imaging findings included hepatomegaly, steatosis or parenchymal heterogeneity. In most patients (5/7), other organs were involved, most commonly with nephrotic syndrome (3/7) and infiltrative cardiomyopathy (3/7). The most common type was AA amyloidosis (3/7) followed by AL amyloidosis (2/7). The 1-year mortality rate was 43% and the median survival was 24 months., Conclusions: We report a low prevalence (0.4%) of amyloidosis among patients undergoing liver biopsy. Although rare, hepatic amyloidosis is associated with a dismal prognosis and a high index of suspicion is crucial to achieve an early diagnosis. .

There is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we present a case of Wolman disease presenting as hepatosplenomegaly in an infant. This case details important learning points to help distinguish the diagnosis of Wolman disease from other conditions with overlapping clinical features, such as hemophagocytic lymphohistiocytosis (HLH). The advent of enzyme replacement therapy has dramatically changed the natural history of Wolman disease, and this child showed remarkable improvement with treatment. This child was later found to have extensive adenopathy with retroperitoneal lymph node biopsy demonstrating diffuse infiltration by lipid-laden macrophages, fatty deposits, cholesterol crystals, and calcifications. Similar to the collection of characteristic cells in other lysosomal storage disorders, we postulate that this is characteristic of underlying Wolman disease. We conclude with a summary of learning points from this presentation on infantile hepatosplenomegaly, pertinent to the geneticist, pediatrician, and pediatric subspecialists., (© 2022 Wiley Periodicals LLC.)

Visceral Leishmaniasis (VL) is endemic in the northeast part of India, principally Bihar, Jharkhand, Uttar Pradesh, and West Bengal. We report a case of VL from the non-endemic Himalayan region of Kashmir. A 25-year-old female presented with a history of fever, generalized weakness, loss of appetite for one month. On clinical examination, there was hepatosplenomegaly and pancytopenia. There was no travel history to any VL endemic areas. Bone marrow examination revealed an amastigote form of Leishmania Donovan. Nested polymerase chain reaction (PCR) confirmed diagnosis. The patient was treated with 6 mg/kg liposomal amphotericin B, for ten days and improved clinically. Our case reveals that VL is expanding towards non-endemic regions of India, and physicians should remember the differential diagnosis of VL in a patient presenting with fever, pancytopenia, and hepatosplenomegaly.

Gaucher disease (GD) is a rare autosomal recessive metabolic disorder. It is characterized by a deficiency of lysosomal glucocerebrosidase, which results in the accumulation of glycosphingolipid substrates, primarily glucosylceramide, in the phagocyte system. In GD Type 1, the liver, spleen, and bone marrow are typically affected. We report the case of a 7-year-old female with GD Type 1 who presented with hepatosplenomegaly detected incidentally following a motor vehicle accident. She was found to have concomitant thrombocytopenia and Erlenmeyer flask deformities of her lower limbs. Diagnosis was made on the basis of very low leukocyte β-glucocerebrosidase activity and elevated plasma chitotriosidase. DNA mutation studies revealed both c.1226A>G and c.116_1505 deletion (exons 3-11). The patient is currently managed with biweekly intravenous imiglucerase (Cerezyme) replacement therapy. She demonstrated resolution of thrombocytopenia and hepatosplenomegaly at 2-year follow-up. Physicians must consider this rare diagnosis in children presenting with hepatosplenomegaly to prompt timely management.

Idiopathic ketotic hypoglycemia (IKH) is a diagnosis of exclusion with glycogen storage diseases (GSDs) as a differential diagnosis. GSD IXa presents with ketotic hypoglycemia (KH), hepatomegaly, and growth retardation due to PHKA2 variants. In our multicenter study, 12 children from eight families were diagnosed or suspected of IKH. Whole-exome sequencing or targeted next-generation sequencing panels were performed. We identified two known and three novel (likely) pathogenic PHKA2 variants, such as p.(Pro869Arg), p.(Pro498Leu), p.(Arg2Gly), p.(Arg860Trp), and p.(Val135Leu), respectively. Erythrocyte phosphorylase kinase activity in three patients with the novel variants p.(Arg2Gly) and p.(Arg860Trp) were 15%-20% of mean normal. One patient had short stature and intermittent mildly elevated aspartate aminotransferase, but no hepatomegaly. Family testing identified two asymptomatic children and 18 adult family members with one of the PHKA2 variants, of which 10 had KH symptoms in childhood and 8 had mild symptoms in adulthood. Our study expands the classical GSD IXa phenotype of PHKA2 missense variants to a continuum from seemingly asymptomatic carriers, over KH-only with phosphorylase B kinase deficiency, to more or less complete classical GSD IXa. In contrast to typical IKH, which is confined to young children, KH may persist into adulthood in the KH-only phenotype of PHKA2., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Rationale: Transient infantile hypertriglyceridemia (HTGTI) is a rare autosomal recessive inherited disease caused by inactivating mutations in the glycerol-3-phosphate dehydrogenase 1 gene. To date, only a few patients have been reported worldwide. The symptoms of the affected individuals present a certain degree of transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis in early infancy. However, the clinical characteristics and pathogenesis of this disease are remain unclear., Patient Concerns: A one month and twenty-five days old girl was admitted to hospital because of persisted jaundice and hepatomegaly for fifty days., Diagnose: The girl was diagnosed with HTGTI coincident with a noval mutation in glycerol-3-phosphate dehydrogenase 1., Intervention: She was advised to take low-fat diet and supplement of medium-chain fatty acids., Outcomes: Her jaundice was gradually normal at the age of 4 months without any treatment, and hypertriglyceridemia were normal at the age of 13 months, but still had elevated transaminases and hepatic steatosis., Lessons: Jaundice may be a novel phenotype in HTGTI. The report contributes to the expansion of HTGTI's gene mutation spectrum and its clinical manifestations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: The aim of this study was to assess the prevalence of liver disease in children and adolescents with type-1 diabetes mellitus (T1DM) by detection of elevated liver transaminases, confirmed by fibroscan and ultrasound. The secondary objective was to assess the effect of glycemic control on improvement of liver functions., Methods: One hundred and seven children and adolescents with T1DM were investigated by liver transaminases, mean HbA1c and pelviabdominal ultrasound while fibroscan was done for those with elevated liver transaminases only. Patients with elevated liver enzymes were reassessed after one year., Results: Only nine (8.4%) of the studied patients have exhibited liver dysfunction in the form of elevated liver transaminases with median ALT 140 U/L and AST 191 U/L and hepatomegaly by ultrasound; The HbA1c (median = 10.8%) and fibroscan abnormalities (median fibrosis score 1) were significantly higher in patients with elevated liver transaminases (p < 0.001). Adequate glycemic control resulted in a significant decrease in liver transaminases (median ALT = 25 U/L and AST = 29 U/L), fibroscan fibrosis score (median = 0) and HbA1c (median = 9%) (p = 0.003), (p = 0.01) and (p = 0.003) respectively., Conclusion: Adequate glycemic control was associated with improvement of liver disease in children and adolescents with diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

As improvements in nutritional and pulmonary care increase the life expectancy of cystic fibrosis (CF) patients, CF-associated liver disease (CFLD) is emerging as a cause of mortality. CFLD is the third leading cause of death in CF patients. We performed a search on PubMed and Google Scholar for published articles on CFLD. We reviewed the articles found in the literature search and gave priority to recent publications and studies with larger sample sizes. The prevalence of CFLD in the CF population is around 23% with a range of 2-62% and that prevalence increases linearly with age from 3.7% at age 5 to 32.2% at age 30. CFLD can present clinically in various ways such as hepatomegaly, variceal hemorrhage, persistent elevation of liver enzymes, and micro-gallbladder. Due to the focal nature of fibrosis in majority cases of CFLD, liver biopsies are sparsely performed for diagnosis or the marker of liver fibrosis. Although the mechanism of CFLD development is still unknown, many potential factors are reported. Some mutations of CFTR such as having a homozygous F508del mutation has been reported to increase the risk of developing CFLD and its severity. Having the SERPINA1 Z allele, a history of pancreatic insufficiency, a history meconium ileus, CF-related diabetes, or being male increases the risk of developing CFLD. Environmental factors do not appear to have significant effect on modulating CFLD development. Ursodeoxycholic acid is commonly used to treat or prevent CFLD, but the efficacy of this treatment is questionable.

Objectives To investigate the clinical and genetic characteristics of children with glycogen storage disease type IIIa (GSD IIIa) and to explore the muscle involvement and manifestations of GSD IIIa patients. Methods The clinical data of 11 patients with GSD IIIa diagnosed by genetic testing from 2003 to 2019 were retrospectively analyzed. Results Twenty variants of AGL gene were detected in 11 patients, eight of which were novel variants. Before treatment, the height was significantly backward. All patients had hepatomegaly. Abnormal biochemical indicators were mainly manifested as significantly increased serum liver and muscle enzymes, accompanied by hypertriglyceridemia, hypoglycemia, hyperlactacidemia, slightly elevated pyruvic acid, and metabolic acidosis. After treatment, the height and liver size of the patients were significantly improved. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), lactic acid and pyruvic acid in children were significantly decreased, while creatine kinase (CK) was significantly increased. During follow-up monitoring, six patients developed ventricular hypertrophy. Lactate dehydrogenase (LDH) (691.67 ± 545.27 vs. 362.20 ± 98.66), lactic acid (3.18 ± 3.05 vs. 1.10 ± 0.40), and pyruvic acid (64.30 ± 39.69 vs. 32.06 ± 4.61) were significantly increased in patients with ventricular hypertrophy compared with those without ventricular hypertrophy. Conclusions In clinical cases of upper respiratory tract infection or gastrointestinal symptoms accompanied by hypoglycemia, dyslipidemia, metabolites disorders, elevated serum liver, and muscle enzymes, the possibility of GSD IIIa should be vigilant. During treatment monitoring, if lactic acid, pyruvic acid, LDH, and CK rise, it indicates that the disease is not well controlled and there is the possibility of cardiac hypertrophy.

Objectives: To improve the diagnostic efficacy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for Chinese patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO), with combined clinical parameters., Materials and Methods: FUO/IUO patients who underwent a standard diagnostic work-up and 18 F-FDG PET/CT scanning were enrolled and divided into a local uptake lesion subgroup and a non-specific abnormal uptake subgroup. Beneficial clinical parameters for improving the diagnostic efficacy of PET/CT were identified., Results: From January 2014 to January 2019, 253 FUO/IUO patients were studied. In total, 147 patients had local uptake lesions and 106 patients had non-specific abnormal uptake. In the local uptake lesion group, the positioning accuracy of PET/CT was 37.2% in grades 1 and 2, and 66.3% in grades 3 and 4. With the following combination of clinical parameters, the positioning accuracy increased to 75.0% and 90.0%, respectively: time from admission to performing PET/CT scanning <6.5 days and C-reactive protein level >95 mg/l. In the non-specific abnormal uptake group, the combination of sex (male), bicytopenia, and lactic dehydrogenase improved the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignancy from 64.3%, 69%, 60%, and 72.7%, respectively, to 83.3%, 81%, 81.4%, and 82.9%, respectively. With the combination of sex (male), white blood count, serum ferritin level, and hepatosplenomegaly, the infection prediction model had a sensitivity, specificity, PPV, and NPV of 78%, 76.2%, 76.6%, and 77.6%, respectively., Conclusions: Combined clinical parameters improved the localization diagnostic value of 18 F-FDG PET/CT in the local uptake lesion subgroup and the etiological diagnostic value in the non-specific abnormal uptake subgroup., (Copyright © 2020. Published by Elsevier Ltd.)

The glycogen storage diseases contain a range of diseases that are characterized by the abnormal storage or utilization of glycogen, the organs most affected being muscle and / or liver. Hepatomegaly may be a clinical sign that could guide to the diagnosis. We describe a 15-year-old patient with hepatomegaly, hypertransaminasemia and growth retardation. He was diagnosed with a glycogen storage disease by liver biopsy.

β-Thalassemia intermedia (β-TI) is a clinical condition characterized by moderate, non transfusional anemia and hepatosplenomegaly. The main objective of this study was to determine the molecular basis of the clinical phenotype of β-TI in Iran. To elucidate the mild phenotype of many patients with β-TI, we screened for three prevalent β-globin gene mutations [IVS-II-1 (G>A) HBB : c.315+1G>A, IVS-I-110 (G>A) HBB : c.93-21G>A and IVS-I-5 (G>C) [ HBB : c.92+5G>C], deletions on the α-globin genes, Xmn I polymorphisms and restriction fragment length polymorphism (RFLP) haplotypes on the β-globin gene cluster in 50 β-TI patients. Fifty-eight percent of the patients (29 cases) were associated with the mentioned mutations. We showed that the HBB : c.315+1G>A mutation is linked to haplotype [+ - + +] (57.69%). This haplotype is in linkage disequilibrium with the Xmn I polymorphism (NG&#95;000007.3: g.42677C>T) and has been associated with increased expression of Hb F in β-TI patients. The Xmn I polymorphism is defined in association with this prevalent mutation. Two patients had a single α-globin gene deletion [-α 3.7 (rightward) deletion]. The main genetic factor in mild phenotype β-TI patients is the linkage of an Xmn I polymorphism (NG&#95;000007.3: g.42677C>T) with the HBB : c.315+1G>A (80.76%), which is associated with increased production of Hb F and coinheritance of haplotype [+ - + +] with β-TI, especially with the homozygous HBB : c.315+1G>A mutation. Molecular basis of β-TI could be explained by the involvement of different factors that tend to develop the disease phenotype.

Constrictive pericarditis is a rare entity in pediatrics in which there is a limitation for cardiac diastole due to fibrosis of the pericardium. The etiopathogenic origin of this pathology is multiple, finding idiopathic constrictive pericarditis firstly and Mycobacterium tuberculosis infection secondly. Diagnosis is a clinical challenge since it requires a high degree of suspicion. It usually presents as oligosymptomatic or with signs and symptoms of low cardiac output. The presence of edema, ascites and impaired liver function usually guides the study towards primary liver disease. A careful clinical history and physical examination together with adequate imaging studies are the cornerstones of the diagnosis. Surgical treatment is curative in the vast majority of patients. We present the case of a 16-yearold patient with hepatomegaly and dyspnea grade 1-2 found in a routine health check-up., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

The association between hypoechoic hepatomegaly in the third trimester and transient abnormal myelopoiesis (TAM) was reported previously in six fetuses with trisomy 21 (T21). We report a series of three cases of T21 in which hypoechoic liver (HL) was found in the second trimester but without evidence of TAM on both hematological and histological examination. We postulate that the hypo-echogenicity may be due to liver congestion secondary to hemodynamic disturbances seen in T21 fetuses. All three cases had negative first trimester Down syndrome screening and one case was detected solely because of the isolated finding of HL. HL per se may be associated with T21 and more positive cases are required to support this association.

Background: Liver hypertrophy induced by partial portal vein occlusion (PVL) is accelerated by adding simultaneous parenchymal transection ("ALPPS procedure"). This preclinical experimental study in pigs tests the hypothesis that simultaneous ligation of portal and hepatic veins of the liver also accelerates regeneration by abrogation of porto-portal collaterals without need for operative transection., Methods: A pig model of portal vein occlusion was compared with the novel model of simultaneous portal and hepatic vein occlusion, where major hepatic veins draining the portal vein-deprived lobe were identified with intraoperative ultrasonography and ligated using pledgeted transparenchymal sutures. Kinetic growth was compared, and the portal vein system was then studied after 7 days using epoxy casts of the portal circulation. Portal vein flow and portal pressure were measured, and Ki-67 staining was used to evaluate the proliferative response., Results: Pigs were randomly assigned to portal vein occlusion (n = 8) or simultaneous portal and hepatic vein occlusion (n = 6). Simultaneous portal and hepatic vein occlusion was well tolerated and led to mild cytolysis, with no necrosis in the outflow vein-deprived liver sectors. The portal vein-supplied sector increased by 90 ± 22% (mean ± standard deviation) after simultaneous portal and hepatic vein occlusion compared with 29 ± 18% after PVL (P < .001). Collaterals to the deportalized liver developed after 7 days in both procedures but were markedly reduced in simultaneous portal and hepatic vein occlusion. Ki-67 staining at 7 days was comparable., Conclusion: This study in pigs found that simultaneous portal and hepatic vein occlusion led to rapid hypertrophy without necrosis of the deportalized liver. The findings suggest that the use of simultaneous portal and hepatic vein occlusion accelerates liver hypertrophy for extended liver resections and should be evaluated further., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We report the case of an adolescent Moroccan girl with abdominal pain and palpable mass in the upper right side of the abdomen. In the emergency department, an abdominal ultrasound showed hepatomegaly and eight active liver cysts, compatible with cystic echinococcosis. Serology for Echinococcus granulosus confirmed the diagnosis. Other sites of localization were excluded. Treatment involved albendazole combined with puncture, aspiration, injection, re-aspiration, performed only for the most medial cysts. Periodical follow-up with abdominal ultrasound and with abdominal magnetic resonance imaging showed a progressive involution of all cysts. The treatment with albendazole was stopped after, overall, 6 months, and monthly ultrasound scan were planned as follow-up. In case of hepatic cysts, E. granulosus should be excluded, especially in children from endemic countries. A multidisciplinary approach with pediatric infectious disease specialists, radiologists, and surgeons is fundamental for disease management.

Objectives: To describe a case of Kawasaki disease with intestinal involvement and to analyze other published reports to define clinical characteristics, diagnostic issues, and therapeutic approaches of gastrointestinal involvement in Kawasaki disease., Study Design: A computerized search without language restriction was conducted using PubMed and SCOPUS. An article was considered eligible for inclusion in the systematic review if it reported data on patient(s) with intestinal involvement in Kawasaki disease. Our case was also included in the analysis., Results: Thirty-three articles reporting 48 cases of Kawasaki disease with intestinal involvement were considered. Fever, abdominal pain, and vomiting were the most frequent symptoms observed and typical Kawasaki disease signs and symptoms appeared after intestinal complaints in all cases. Plain radiographs, ultrasonography, and computed tomography showed pseudo-obstruction as the most frequent sign of gastrointestinal involvement; 25 patients underwent surgery. Cardiac involvement was documented in 21 cases. All but three patients received medical treatment with immunoglobulin intravenous or aspirin. The outcome was good in 28 patients; 7 patients showed persistence of coronary artery abnormalities; 1 patient developed cyanosis, and later, left hand and forefoot gangrene; 3 patients died., Conclusions: The diagnosis and treatment of Kawasaki disease might be delayed if intestinal symptoms appear before the characteristic clinical features of Kawasaki disease, thus, increasing the risk of cardiac complications. Furthermore, patients may undergo unnecessary invasive procedures. Pediatricians and pediatric surgeons, therefore, should consider Kawasaki disease among diagnoses in children with fever, abdominal symptoms, and radiologic findings of pseudo-obstruction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Gaucher disease is a rare pan-ethnic disorder which occurs due to an increased accumulation of undegraded glycolipid glucocerebroside inside the cells' lysosomes. A beta-Glucosidase (GBA) gene defect results in glucocerebrosidase enzyme deficiency. Though the disease is mainly diagnosed in childhood, the adult manifestation is often missed or identified late due to the failure to recognize the heterogeneous clinical presentation. The present study includes seven unrelated Indian adult patients (age range: 20-40 years) having splenomegaly, with or without hepatomegaly, cytopenia and bone abnormality., Methods: The biochemical investigation implicated measuring plasma chitotriosidase enzyme activity followed by confirmatory test of β-Glucosidase enzyme activity from the leukocytes. The molecular characterization involved patients' initial screening for the common Gaucher mutation (Leu444Pro). Later, all patients were subjected to whole GBA gene coding region study using bidirectional Sanger sequencing. The population screening for common Gaucher disease mutation (Leu444Pro) was executed in 1200 unrelated and healthy Indian subjects by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction technique. The allele frequency was calculated using Hardy-Weinberg formula., Results: The biochemical analysis revealed a significant reduction in the β-Glucosidase activity in all the patients. Also, an elevated level of plasma Chitotriosidase activity in five patients supported their diagnosis of Gaucher disease. Sanger sequencing established four patients with homozygous variation and three patients with compound heterozygous variation in GBA gene. This study uncovers two missense variants (Ala448Thr and Val17Gly) not previously reported in Gaucher disease patients. Also the known mutations like Leu444Pro, Arg329Cys, Asp315Asn, Ser125Arg, and Arg395Cys were identified in these patients. The homology modeling suggested the destabilization of the protein structure due to novel variants. The Leu444Pro mutation screening in the Indian population spotted two people as a carrier. This emerged the carrier frequency of 1:600 along with wild-type allele frequency 0.97113 and mutant allele frequency 0.02887., Conclusions: The study reports novel and known variants identified in the GBA gene in seven adult patients. The given study is the first report on the carrier frequency of the Leu444Pro mutant allele in an Indian population which will help understanding the burden and susceptibility of Gaucher disease to affect next generation in India.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal lipid storage disorder that results in an early-onset, severe, and lethal phenotype, known as Wolman disease, or a late-onset, attenuated phenotype, cholesteryl ester storage disease (CESD). The aim of our study was to describe the clinical presentation of CESD, focusing on the first noted abnormalities in patients. A diagnostic algorithm of CESD was also proposed., Methods: This is an observational, 1-center study of 19 Polish patients with late-onset LAL-D., Results: The mean age at which the first symptoms were reported was 4 years and 6 months. A mild hepatomegaly was the most common initial abnormality observed in all (100%) patients. Seven (37%) patients were noted to have mildly to moderately elevated serum transaminases. At the time of first hospitalization all (100%) patients presented with hepatomegaly, 15 (79%) patients presented with elevated serum transaminases and all (100%) patients had dyslipidemia. The mean age at the time of CESD diagnosis was 7 years and 2 months. Diagnoses were based on a deficient LAL activity in leukocytes (in all patients) and the LIPA gene mutations (in 47% of them). All the patients were carriers for the mutation c.894G>A in the LIPA gene. There was approximately a 3-year delay from initial symptoms to final diagnosis., Conclusions: Hepatomegaly constitutes the most common presenting clinical sign of CESD. Hepatomegaly and dyslipidemia defined as elevated serum total and LDL cholesterol, elevated triglycerides and normal to low HDL cholesterol, comprises the most characteristic findings at CESD diagnosis.

Rationale: TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome., Patient Concerns: Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly., Diagnoses: In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis., Interventions and Outcomes: In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy., Lessons: This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

The article presents the results of our own studies to determine the criteria for the adverse variants of the course of infectious mononucleosis (IM) in children. The study was conducted in the regional children's infectious clinical hospital in Kharkov. 161 children aged three to fifteen years were under observation with diagnosis of infectious moninucleosis. Out of 161 ill children, 140 (86.9%) had moderate severity of disease, and 21 (13.1%) had severe forms. All children were prescribed standard clinical and laboratory-instrumental examinations. The diagnosis of IM was verified by PCR (detection of VEB DNA in the blood) and ELISA (anti-VEB Ig M and Ig G). In 140 children (86.9%) IM proceeded sharply, smoothly (the first group), in 21 (13.1%) - unfavorably (wave and / or prolonged course) - the second group. The groups were comparable according to age, the severity of the disease and other parameters. All children received therapy according to approved protocols (Order of the Ministry of Health of Ukraine No. 354 of 09.07.2004). Immune status of children was assessed by determining the relative contents of CD3 +, CD4 +, CD8 +, CD16 +, CD19 + blood cells with appropriate monoclonal antibodies, serum IgA, IgM, IgG concentration by Mancini and interleukin (IL) -1β cytokine response and - 4, tumor necrosis factor (TNF α) is a solid-phase enzyme-linked immunosorbent assay. Based on the results of observations, it was established that the prognostically unfavorable criteria of IМ at the stages of manifestation of disease include: generalized lymphadenopathy involving 5-6 groups of lymph nodes and a significant increasing of them, purulent tonsillitis, marked increasing of size of liver and spleen on the background of anemia, thrombocytopenia, neutropenia and the absence of atypical mononuclears in the complete blood count. There is a depression of the cellular link and an increase in the humoral mechanisms of immune responses in case of development of adverse course of IM.

Background: Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive ones., Data Sources: A PubMed database search (up to July 1, 2017) was done with the words "glycogenic hepatopathy", "hepatic glycogenosis", "liver glycogenosis" and "diabetes mellitus-associated glycogen storage hepatopathy". Articles in which diabetes mellitus-associated liver glycogen accumulation was described were included in this review., Results: A total of 47 articles were found, describing 126 patients with GH. Hepatocellular disturbance was more profound than cholestatic disturbance. No synthetic failure was reported., Conclusions: GH may be diagnosed conservatively, based on corroborating medical history, physical examination, laboratory tests, imaging studies and response to treatment, even without liver biopsy. In case of doubt about the diagnosis or lack of clinical response to treatment, a liver biopsy may be considered. There is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease., (Copyright © 2018. Published by Elsevier B.V.)

Sickle Cell Disease (SCD) is a structural haemoglobinopathy which is extremely diverse in its presentation regarding disease severity and organ involved. The homozygous form if poorly managed gives rise to numerous life threatening conditions which are otherwise avoidable. Here we report the case of a male adolescent with homozygous SCD who presented with haemolytic anaemia, massive ascites, hepatomegaly and multiple fractures secondary to severe malnourishment associated with the disease.

Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation caused by monogenic mutations resulting in cytotoxic cell defects and subsequent failure to eliminate activated macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian inheritance. However, some cases of "secondary" HLH have been shown to harbor mutations with partial dysfunction of the cytotoxic system. Recently, macrophage intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked to autoinflammation and recurrent macrophage activation syndromes resembling a primary HLH. We report a case of a former 28-week preterm infant with congenital anemia, ascites, and a heavy edematous placenta with fetal thrombotic vasculopathy, who developed hepatosplenomegaly and unexplained systemic inflammation with laboratory features of HLH in the early postnatal course and died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in the bone marrow and lymph nodes. There was extensive acute and chronic ischemic bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing enterocolitis features. Whole exome sequencing analysis demonstrated a novel mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to cause a dominant, gain-of-function mutation resulting in a constitutively active protein. The assembly of NLRC4-containing inflammasomes via an induced self-propagation mechanism likely enables a perpetuating process of systemic macrophage activation, presumed to be initiated in utero in this patient.

Background and Aims: Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D., Methods: Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients., Results: LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype., Conclusions: This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene., (Copyright © 2017. Published by Elsevier B.V.)

Background: Glycogen storage disease type VI (GSD-VI) presents with failure to thrive and also fibrosis in some cases, without cirrhosis., Case Characteristics: 2½-year-old girl presented with short stature, transaminase elevation and significant fibrosis, suggesting GSD-III., Observation: A pathogenic mutation in PYGL gene suggested GSD-VI., Message: GSD-VI should be a differential diagnosis whenever GSD-III is suspected.

Purpose: To compare point-of-care ultrasound and physical examination (PEx), each performed by first-year medical students after brief teaching, for assessing ascites and hepatomegaly. Ultrasound and PEx were compared on: (1) reliability, validity and performance, (2) diagnostic confidence, ease of use, utility, and applicability., Methods: A single-center, randomized controlled trial was performed at a tertiary centre. First-year medical students were randomized to use ultrasound or PEx to assess for ascites and hepatomegaly. Cohen's kappa and interclass coefficient (ICC) were used to measure interrater reliability between trainee assessments and the reference standard (a same day ultrasound by a radiologist). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were compared. A ten-point Likert scale was used to assess trainee diagnostic confidence and perceptions of utility., Results: There were no significant differences in interobserver reliability, sensitivity, specificity, accuracy, PPV, or NPV between the ultrasound and PEx groups. However, students in the ultrasound group provided higher scores for perceived utility (ascites 8.38 ± 1.35 vs 7.08 ± 1.86, p  = 0.008; hepatomegaly 7.68 ± 1.52 vs 5.36 ± 2.48, p  < 0.001) and likelihood of adoption (ascites 8.67 ± 1.61 vs 7.46 ± 1.79, p  = 0.02; hepatomegaly 8.12 ± 1.90 vs 5.92 ± 2.32, p  = 0.001)., Conclusions: When performed by first-year medical students, the validity and reliability of ultrasound is comparable to PEx, but with greater perceived utility and likelihood of adoption. With similarly brief instruction, point-of-care ultrasonography can be as effectively learned and performed as PEx, with a high degree of interest from trainees.

We report the first case of haemophagocytic lymphohistiocytosis (HLH) in a neonate secondary to primary Dengue virus infection. This neonate presented in the third week of life with fever, shock and hepatosplenomegaly and was diagnosed to have Dengue infection by serology and HLH was confirmed on bone marrow.

Purpose: To describe a case of hemophagocytic lymphohistiocytosis (HLH) with ocular changes prior to the systemic changes., Methods: A 53-year-old man presented with the chief complaint of decreased vision in his right eye. The patient was examined by ocular examination, slit lamp examination, optical coherence tomography, laboratory examination, abdominal ultrasound, and bone marrow biopsy., Results: Ocular examination revealed uveitis OD and optical coherence tomography revealed macular edema OD. Laboratory examination demonstrated cytopenia in two cell lines, hypofibrinogenemia, and elevated serum ferritin. Abdominal ultrasound findings indicated hepatosplenomegaly. The bone marrow biopsy specimen demonstrated histiocytes and significant hemophagocytosis, leading to a diagnosis of HLH., Conclusion: Ophthalmic manifestation can be the first sign of HLH and progress to fatal systemic changes.

Introduction: Hepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated., Case Report: An 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder., Conclusion: Excess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

We report a full-term neonate presenting with symptomatic congenital cytomegalovirus (CMV) infection with hepatosplenomegaly, 'blueberry muffin' rash, intracranial calcifications, thrombocytopenia and respiratory distress. Maternal history was relevant for Guillain-Barré syndrome (GBS) during the first trimester of pregnancy. CMV infection is an important cause of GBS; thus, women presenting GBS during pregnancy should be screened for CMV infection. If positive, they may benefit from specialised monitoring and treatment in the antenatal period, which may decrease the risk of major neurodevelopmental sequelae of congenital CMV in the neonate., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS.

Mauriac syndrome is characterized by growth impairment, Cushingoid features, and hepatomegaly in patients with poorly controlled type 1 diabetes mellitus (T1DM). We report a novel presentation of Mauriac syndrome in a 9-year-old girl who was diagnosed with neonatal diabetes at 3 months of age due to the p.R201C mutation in KCNJ11. She was initially treated successfully with glipizide at a dose of 0.85 mg/kg/day but after being lost to follow-up and having improper adjustment in dose over many years, the recent dose of 0.6 mg/kg/day appears to have been insufficient for glycemic control but enough to maintain a low level of C-peptide and prevent diabetic ketoacidosis. With proper insulin administration, all presenting clinical characteristics were resolved within 1 month. A review of the literature relating to clinical manifestations of Mauriac syndrome in children with diabetes was performed and included in this report for comparison with our patient. While Mauriac syndrome has been traditionally associated with T1DM, the presence of Mauriac syndrome should not be excluded in other types of diabetes mellitus.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by defective lytic capability of cytotoxic T lymphocytes and NK cells, which results in proliferation of benign hemophagocytic histiocytes. A cytokine storm ensues, and a severe systemic inflammatory response syndrome, multiorgan dysfunction syndrome, and death frequently follow. It may occur as a primary (inherited) form, or be acquired secondary to malignancy, infection, rheumatologic disease, or immunosuppression. Cardinal manifestations include fever, cytopenias, hepatosplenomegaly, and dysfunction of liver, kidney, CNS, and/or lung. Additional laboratory findings include marked hyperferritinemia, hypofibrinogenemia, hypertriglyceridemia, abnormal LFTs, coagulopathy, and hyponatremia. Nephrologists need to be aware of this syndrome owing to the frequent occurrence of acute kidney injury in these severely ill patients. Glomerulopathy and nephrotic syndrome may develop. Kidney transplant recipients are at increased risk of HLH due to immunosuppression, and most such cases are triggered by infection with over 50 % mortality. Effective treatment of HLH usually requires chemoimmunotherapy to acutely suppress inflammation, specific treatment of underlying infection or malignancy, and in certain cases hematopoietic stem cell transplantation. The pathogenesis, clinical manifestations, diagnosis, and treatment of HLH are discussed.

Unlabelled: Sialuria, a rare inborn error of metabolism, was diagnosed in a healthy 12-year-old boy through whole exome sequencing. The patient had experienced mild delays of speech and motor development, as well as persistent hepatomegaly. Identification of the 8th individual with this disorder, prompted follow-up of the mother-son pair of patients diagnosed over 15years ago. Hepatomegaly was confirmed in the now 19-year-old son, but in the 46-year-old mother a clinically silent liver tumor was detected by ultrasound and MRI. The tumor was characterized as an intrahepatic cholangiocarcinoma (IHCC) and DNA analysis of both tumor and normal liver tissue confirmed the original GNE mutation. As the maternal grandmother in the latter family died at age 49years of a liver tumor, a retrospective study of the remaining pathology slides was conducted and confirmed it to have been an IHCC as well. The overall observation generated the hypothesis that sialuria may predispose to development of this form of liver cancer. As proof of sialuria in the grandmother could not be obtained, an alternate cause of IHCC cannot be ruled out. In a series of 102 patients with IHCC, not a single instance was found with the allosteric site mutation in the GNE gene. This confirms that sialuria is rare even in a selected group of patients, but does not invalidate the concern that sialuria may be a risk factor for IHCC., Synopsis: Sialuria is a rare inborn error of metabolism characterized by excessive synthesis and urinary excretion of free sialic acid with only minimal clinical morbidity in early childhood, but may be a risk factor for intrahepatic cholangiocarcinoma in adulthood., (Copyright © 2016 Elsevier Inc. All rights reserved.)