Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by spherical erythrocytes, splenomegaly, and increased osmotic fragility, with ANK1 mutations being the most frequent cause. We identified a novel ANK1 mutation (c.5096G>A, p.R1699K) in a patient with classic HS phenotypes and a family history of hemolytic anemia. To explore its pathogenicity, we performed a series of hematological and morphological analyses. Compared with wild-type mice, the Ank1 c.5198G>A knock-in mice displayed typical HS features. Hematologically, they showed reduced MCV, MCH, and MCHC. The EMA fluorescence intensity was significantly decreased, and RBCs exhibited increased osmotic fragility. Morphologically, peripheral smears revealed abundant spherocytes, and electron microscopy showed a transformation from normal biconcave discs to spherical erythrocytes. Additionally, the Ank1 c.5198G>A knock-in mice presented with significant splenomegaly. Mechanistically, coimmunoprecipitation analysis indicated a significantly weakened association between ankyrin-1 and β-spectrin in the Ank1 c.5198G>A knock-in mice. This study provides in vivo evidence that the Ank1 R1733K mutation impairs erythrocyte membrane stability and cytoskeletal integrity, recapitulating the HS phenotype in mice. Our findings support the pathogenicity of the ANK1 c.5096G>A mutation and offer a useful model for further investigating the molecular mechanisms of HS.

Classic myeloproliferative neoplasms, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are chronic, clonal hematopoietic stem-cell disorders. These disorders are driven by gain-of-function mutations in the genes Janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL) that activate cytokine signaling. These mutations arise decades before clinical disease develops and confer a clonal advantage that is further shaped by comutations in epigenetic, splicing, or signaling genes. Inflammation enhances clonal dominance, favoring the development of myelofibrosis and thrombotic complications. Disease evolution may culminate in secondary acute myeloid leukemia, which has a poor prognosis. Current therapies primarily aim to control symptoms, thrombosis, and splenomegaly, but they have limited disease-modifying effects, except for pegylated interferon alfa and JAK2 inhibitors in some patients. Emerging therapies that selectively target mutant CALR and JAK2 V617F using immunotherapy and selective inhibitors could be a breakthrough in the treatment of persons with myeloproliferative neoplasms, with the expectation of achieving durable disease modification and potentially clonal eradication.

We report a rare long-term case in which systemic polyarteritis nodosa (PAN) was ultimately diagnosed in adulthood after childhood-onset recurrent inflammatory disease with atypical Still-like features. A Japanese man had recurrent febrile episodes from infancy and was diagnosed with juvenile idiopathic arthritis at 9 years of age. In early adulthood, he developed recurrent fever, rash, polyarthralgia, splenomegaly, neutrophilia, and elevated inflammatory markers, and was considered to have Still-spectrum disease. However, ferritin elevation remained modest despite marked systemic inflammation, suggesting that the early phenotype may not have represented typical Still's disease and may instead have reflected a broader autoinflammatory process. At 25 years of age, he developed digital ischaemia with necrosis, palpable nodules, and erectile dysfunction. Angiography demonstrated narrowing of the ulnar and palmar arteries, and skin biopsy showed necrotising vasculitis involving medium-sized vessels, leading to the diagnosis of systemic PAN. He subsequently developed fever, rash, inner-ear involvement, hypertrophic pachymeningitis, and tortuosity/dilatation of a right intercostal artery. A subtle suspected lesion of the right testicular artery later became a definite enlarging aneurysmal lesion on serial imaging. Systemic inflammatory manifestations were subsequently controlled during treatment that included glucocorticoids, azathioprine, and tocilizumab. However, serial imaging demonstrated gradual enlargement of the right testicular artery aneurysmal lesion despite the absence of fever, rash, or C-reactive protein elevation for 5 years. This clinical course suggests that vascular progression may not always be adequately reflected by C-reactive protein levels during interleukin-6 blockade. This case illustrates the diagnostic difficulty of childhood-onset recurrent inflammatory disease with atypical Still-like features that was ultimately recognized as systemic PAN in adulthood. Occult or under-recognized medium-vessel vasculitis may have been present earlier in the disease course. Long-term diagnostic reappraisal, vascular imaging when indicated, and continued follow-up across paediatric and adult rheumatology care may therefore be important in similar patients, particularly in the current biologic era.

Niemann-Pick type C disease (NP-C) is a rare neurovisceral disorder caused by mutations in the NPC1 or NPC2 genes. Clinical symptoms of NP-C can appear at any age. Here we report a case of a girl diagnosed with NP-C who subsequently developed central precocious puberty (CPP). To our knowledge, this association has not been described in the literature till now. An 8 year old girl was referred to the pediatric metabolism outpatient clinic due to poor school performance, behavioral changes and periventricular white matter signal changes observed on cranial magnetic resonance imaging (MRI). The physical examination revealed vertical supranuclear gaze palsy (VSGP) and splenomegaly. The patient was diagnosed NP-C through genetic analysis and was started miglustat treatment. The patient was also referred to the pediatric endocrinology outpatient clinic due to breast development (Tanner stage 3) and pubic hair (Tanner stage 3). Laboratory work up revealed normal basal serum LH (0. 2 U/L) and the LHRH test showed a LH value of 8.48 U/L and a peak LH/ FSH ratio of 2. 8 (>0.66). Pelvic ultrasonography revealed an uterine length of 45 mm and mean ovarian volume of 5. 5 mL, Leuprolide acetate was started and at the first year of follow-up the patient's height velocity was 0.4 SDS and Tanner's pubertal staging was 3. This case report highlights a potential association of NP-C with CPP and confirms the need for careful assessment of pubertal development in patients with white matter disease.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by excessive production of one or more mature myeloid lineages. The JAK2 V617F point mutation - present in nearly all patients with polycythemia vera (PV) and in approximately 50% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF) - is the principal molecular driver in Philadelphia chromosome (Ph)-negative MPNs. This review, conducted in accordance with PRISMA 2020 guidelines, aimed to evaluate the clinical manifestations (thrombosis, splenomegaly, and bleeding), hematological parameters, serum lactate dehydrogenase (LDH) levels, and risk of disease progression to acute leukemia or myelofibrosis associated with the JAK2 V617F mutation. A comprehensive literature search was performed across PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published between 2005 and 2025. Following screening of 1,100 candidate records, 10 primary studies encompassing 3,311 patients were included in the final synthesis. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The included studies demonstrate that the majority of JAK2 V617F-positive MPN patients are older than 50 years, with no marked sex predilection. Splenomegaly and thrombotic events were frequently reported across cohorts. Serum LDH levels, hematocrit, and hemoglobin were consistently elevated, while leukocytosis was the predominant hematological finding, though white blood cell (WBC) counts varied widely across MPN subtypes. A minority of patients demonstrated disease transformation to acute leukemia or myelofibrosis. These findings underscore the central prognostic and diagnostic significance of JAK2 V617F in Ph-negative MPNs and highlight its value in clinical risk stratification and therapeutic monitoring.

Objective: To investigate the clinical features of regional portal hypertension (RPH) in children whose primary presentation was isolated gastric fundal varices. Methods: This case series study reviewed clinical data from 8 children diagnosed with RPH complicated with isolated gastric fundal varices at Beijing Children's Hospital, Capital Medical University from June 2017 to January 2026. Data on demographics, clinical manifestations, laboratory findings, diagnosis, and treatment were extracted and analyzed for etiology, clinical characteristics, and outcomes. Results: Among 8 children there were 6 males and 2 females, with a diagnostic age of 2.2-11.5 years. The underlying etiologies were pancreatic in 6 children (5 with severe pancreatitis complicated by pancreatic pseudocyst, and 1 with pancreatic involvement secondary to acute leukemia), all involving pancreatic body and tail. One child was of splenic origin (disseminated tuberculosis with splenic involvement), and 1 child was retroperitoneal (secondary to retroperitoneal neuroblastoma). Presenting features included abdominal pain (7 children), vomiting (6 children), and gastrointestinal bleeding (2 children, 1 of whom with isolated hematemesis, another 1 with hematemesis and melena). Splenomegaly occurred in 7 children. Ascites observed in 5 children, was attributed to the primary disease rather than to RPH. All 8 children had normal platelets, 3 children presented with leukopenia and anemia, which were attributed to the primary disease and secondary lesions. All 8 children had normal liver function, and coagulation function, but all demonstrated splenic vein abnormalities. All 8 children received treatment targeting at the underlying etiology. Somatostatin was administered to 5 children, and hemostatic agents to the 2 children with gastrointestinal bleeding. No child underwent endoscopic intervention. The follow-up ranged from 2 months to 8 years; 1 child with tuberculosis was lost to follow-up. The remaining 7 children showed symptomatic relief and improvement or complete resolution of gastric fundal varices. Conclusions: Regional portal hypertension often manifests as isolated gastric fundus varices and splenomegaly, and may be accompanied by gastrointestinal bleeding. Pancreatic, splenic, and retroperitoneal etiologies should be vigilanted. Individualized treatment strategies focused on the primary disease are crucial for improving pediatric RPH outcomes.

The spleen is usually viewed as a hematologic, vascular and immune organ, but rarely within lipid-associated disease. This review proposes splenic steatopathy as a provisional clinical and experimental framework rather than an established diagnosis or a splenic equivalent of fatty liver disease. Evidence is organized into pre-splenic drivers, intra-splenic pathology and post-splenic consequences. Upstream drivers include metabolic dysfunction-associated steatotic liver disease, obesity, severe hypertriglyceridemia, lysosomal storage disorders, drug-induced phospholipidosis, altered lymphatic lipid handling and portal-hemodynamic stress. Spleen-level findings include altered volume, attenuation, stiffness or metabolic activity; lipid-laden histiocytes; lysosomal or phospholipid storage; and immune-cell remodeling. Potential downstream relevance includes cytopenias, immune dysfunction, infection vulnerability, diagnostic redirection, cancer-associated immune biology and perioperative risk. Human evidence currently consists mainly of observational imaging studies and rare tissue reports; animal studies provide mechanistic support, while several proposed clinical links remain hypotheses. No validated diagnostic criteria, imaging thresholds or biomarkers currently exist. The framework may help distinguish unexplained splenomegaly from common mimics and, if validated, support long-term risk stratification for infection and malignancy in patients with metabolic liver disease. Future studies should prioritize spleen-specific imaging methods, tissue-imaging correlation, lipidomics, immune phenotyping and prospective outcome validation.

Shear wave elastography is a non-invasive ultrasound technique that quantifies tissue stiffness with high reproducibility. While its role in assessing portal hypertension is well established, the spleen has recently gained attention as a potential biomarker in non-portal conditions. As a vascular and immune organ, the spleen undergoes structural and functional changes in various systemic diseases, making splenic shear wave elastography a promising diagnostic and prognostic tool. This review summarizes current evidence regarding splenic shear wave elastography in healthy individuals and in diseases beyond portal hypertension. In hematologic disorders, particularly myeloproliferative neoplasms, splenic stiffness correlates with bone marrow fibrosis, extramedullary hematopoiesis, and thrombotic complications. In cardiovascular conditions, splenic congestion reflects systemic venous pressure and has been studied in acute and chronic heart failure, as well as in congenital circulatory alterations such as Fontan physiology. Research in inherited storage diseases, transfusion-dependent anemias, and autoinflammatory syndromes suggests a role for shear wave elastography in detecting parenchymal infiltration and monitoring disease progression. Infectious diseases including brucellosis, schistosomiasis, and HIV-related vasculopathy, further highlight its sensitivity to microvascular and inflammatory changes. Pediatric studies have expanded normative reference ranges and explored applications in systemic infections and splenomegaly. Despite encouraging findings, methodological heterogeneity, variability among ultrasound platforms, and physiological confounders limit comparability across studies. Current evidence remains predominantly based on small, single-center cohorts, and disease-specific cutoff values have yet to be established. In conclusion, splenic shear wave elastography shows potential for broad clinical applicability, but standardization of protocols, multicenter validation, and integration into multiparametric ultrasound frameworks are needed before implementation in routine practice.

Erythropoietic protoporphyria (EPP) is a disease caused by an inborn error of heme biosynthesis. It manifests as painful photosensitivity in childhood. Liver disease occurs due to the deposition of protoporphyrin. Cholestasis due to protoporphyrin leads to a vicious cycle of worsening, which can lead to liver failure. A 29-year-old woman presented with a three-month history of intermittent low-grade fever and a one-month history of jaundice. She had a history of painful blisters over the skin in childhood that started at two years of age and progressed to multiple contractures from healed ulcers by five years of age. She also had splenomegaly on examination. Her blood tests showed pancytopenia, hyperbilirubinemia, and elevated liver enzymes. Tropical fever workup was negative. Autoimmune hepatitis was considered, as antinuclear antibodies (ANA) were positive with elevated immunoglobulin G (IgG). Skin biopsy showed features suggestive of lipoid proteinosis. However, on review with Periodic Acid-Schiff-diastase (PAS-D) staining, a close mimic, EPP was considered a possibility. Liver biopsy showed features of EPP with infiltration with refractile brown pigment showing bright-red birefringence on polarizing microscopy. Next-generation sequencing (NGS) confirmed EPP with a ferrochelatase enzyme coding gene mutation. The patient developed pneumonia during hospitalization and developed acute on chronic liver failure (ACLF) grade 3a, as defined by the European Association for the Study of the Liver (EASL), with ascites and encephalopathy. She was treated with photoprotective measures, ursodeoxycholic acid, antibiotics, and supportive care. The family was counseled regarding options for sequential hepatic and bone marrow transplants. She was managed with the best supportive care.

Myelofibrosis is an advanced myeloproliferative neoplasm that is biologically driven by constitutively active JAK-STAT signaling. Resultant effects on hematopoiesis and inflammatory cytokine signaling give rise to an array of clinical manifestations that include proliferative features, splenomegaly, constitutional symptoms, cytopenias, propensity towards leukemic transformation, and risk of thrombosis, with patients exhibiting a high degree of variability in regard to clinical course. This necessitates an individualized treatment approach that accounts for a variety of clinical and therapy-specific factors. JAK inhibitors have emerged as the cornerstone of therapy. With 4 agents now approved in the class, selecting the appropriate agent is of critical importance. In this review we discuss key variables that should be considered in the creation of a therapeutic plan for patients with myelofibrosis. We will review pharmacologic differences between available JAK inhibitors, discuss the patient factors that drive therapy decisions in myelofibrosis, and highlight emerging therapies in the field.