The assessment of dysmorphic red blood cells (RBCs) is of significant clinical interest in the evaluation of haematuria, particularly as a key tool for suggesting a possible glomerular origin. However, its actual utility depends on cautious, context-based interpretation supported by well-defined technical requirements. The lack of universal standardization, interobserver variability, and the influence of preanalytical factors continue to contribute to the heterogeneous implementation of this test in clinical practice. This document provides recommendations aimed at optimizing its use in the clinical laboratory. It reviews the underlying pathophysiological basis, principal indications, and the preanalytical and analytical conditions required to ensure reliable evaluation, as well as its integration with other findings from urinalysis and renal biochemistry. In this regard, erythrocyte dysmorphism should not be considered an isolated test, but rather a complementary parameter whose diagnostic performance improves when interpreted alongside proteinuria or albuminuria, renal function, the presence of pathological casts, and the patient's clinical context. Furthermore, the importance of a selective approach is emphasized, prioritizing clinical scenarios with higher diagnostic yield, such as persistent microhaematuria, haematuria associated with proteinuria, or suspected glomerular disease. Finally, guidance criteria are proposed for reporting and for integration into multidisciplinary clinical algorithms. Overall, these recommendations aim to promote a more rational, harmonized, and clinically meaningful use of dysmorphic RBC counts within advanced urinalysis.

Red blood cells (RBCs) rely on their mechanical and electrostatic properties to maintain microvascular circulation and oxygen delivery. Oxidative stress, a hallmark of many diseases, disrupts these properties by damaging membrane lipids and cytoskeletal proteins. In this study, RBCs from healthy donors were incubated with three oxidative agents, i.e., phenylhydrazine (PHZ), tert-butyl hydroperoxide (t-BHP), and diamide, to investigate how oxidative stress affects the combination of single-cell mechanical, morphological, biochemical, and electrical properties under different oxidizing conditions. All oxidants significantly increased intracellular reactive oxygen species (iROS), with PHZ producing the strongest effect. Morphological analysis revealed acanthocyte and echinocyte formation and a reduced cell diameter. Zeta potential (ζ) remained unchanged across treatments when measured in phosphate-buffered saline (PBS) solution, suggesting a preserved surface charge under these conditions. Mechanical properties were assessed by optical tweezers at the single-cell level to estimate overall elasticity and bending modulus. Untreated and t-BHP-treated RBCs showed comparable elasticity and bending modulus. Diamide increased overall elasticity and slightly elevated bending modulus, while PHZ severely impaired elongation capability, inducing an irregular trapping behavior and prohibiting the calculation of the bending modulus. These findings demonstrate that oxidative stress exerts agent-specific effects on RBC biomechanics, with t-BHP inducing mild alterations, diamide increasing elasticity, and PHZ causing profound damage. To our knowledge, this is the first study to directly correlate oxidative damage, mechanical stiffness, and electric properties across single-cell and population scales, providing a comprehensive evaluation of RBC responses to oxidative injury.

A 29-year-old woman with a novel homozygous VPS13A frameshift variant presented with drug-resistant temporal-lobe epilepsy and severe sensory neuronopathy, but no acanthocytes on repeated blood smears-expanding the phenotypic spectrum of chorea-acanthocytosis beyond its defining haematological feature.

Spur cell anemia (SCA) is a rare but severe form of acquired hemolytic anemia seen in advanced cirrhosis and carries a poor prognosis in the absence of liver transplantation. We report the case of a middle-aged man with alcohol-related cirrhosis who developed profound anemia requiring recurrent transfusions. An extensive workup was performed to rule out other causes of anemia, including gastrointestinal bleeding, microangiopathic hemolytic anemia, and autoimmune hemolytic anemia. Peripheral smear confirmed the presence of acanthocytes, consistent with SCA. Given that he was not a transplant candidate, supportive transfusions were provided, but his condition deteriorated rapidly, and he died within one month of diagnosis. This case highlights the aggressive course of SCA in non-transplant candidates and underscores the need for further research into alternative therapies.

OBJECTIVES: To address the limitations of microscopy and current automated instruments, we analyzed 11 red blood cell (RBC) morphological parameters generated by the EH-2090 analyzer. We aimed to identify dysmorphic RBCs associated with glomerular hematuria (GH), establish optimal diagnostic thresholds, and develop a predictive model for GH based on urinalysis features. METHODS: A total of 597 hematuria samples were collected from patients across eight hospitals. The 11 RBC morphological parameters were compared with the final clinical diagnosis. The parameter yielding the largest area under the curve (AUC) was identified as being associated with GH, and its optimal diagnostic cutoff value was determined. Nine machine learning (ML) models were constructed. Receiver operating characteristic (ROC) and precision-recall (PR) curves were used to evaluate the models’ performances, and the SHapley Additive exPlanations (SHAP) method was used for visual analysis of the model with the optimal performance. RESULTS: The results confirmed that acanthocytes, jagged RBCs, annular RBCs, and other dysmorphic RBCs offered the greatest clinical value for diagnosing GH. When the combined proportion of these four dysmorphic RBC types exceeded 26% of the total erythrocytes, the sensitivity and specificity for diagnosing GH were 92.2% and 81.7%, respectively, with an AUC of 0.907. Among the constructed diagnostic models for GH, the random forest (RF) model demonstrated the best performance, with an AUC of 0.960. Confusion matrix analysis of the validation set showed a sensitivity of 96.6% and a specificity of 85.9%. CONCLUSION: The EH-2090’s identification of dysmorphic RBCs demonstrated high sensitivity and accuracy in distinguishing GH from non-glomerular hematuria (NGH), offering a rapid, automated, and standardized detection method.

Chorea-acanthocytosis (ChAc) is a rare genetic disorder characterised by a hyperkinetic movement disorder, dystonia, cognitive and neuropsychiatric deficits and seizures. We report the case of a 30-year-old patient who presented with a decade of episodic neurological dysfunction and seizures. The condition was initially suspected to be an immunotherapy-responsive seronegative autoimmune encephalitis but progressed to oromandibular dystonia, raising suspicion of a neurodegenerative condition. Neuroimaging showed bilateral caudate atrophy and acanthocytes were seen on blood film microscopy in association with raised creatine kinase. Genetic testing revealed our patient to be compound heterozygous for two pathogenic variants in the VPS13A gene and confirmed the diagnosis of ChAc. This case highlights the importance of considering ChAc in the differential diagnosis of a progressive treatment-refractory seizure disorder in the context of oromandibular dystonia.

VPS13A disease is a rare, autosomal-recessive, neurodegenerative disorder characterized by involuntary movements, orofacial dystonia, seizures, psychiatric symptoms, and the presence of spiky, deformed red blood cells (acanthocytes). The disease is caused by mutations in the VPS13A gene, which encodes the VPS13A protein (previously known as chorein). This protein is a member of the family of bridge-like lipid transport proteins, involved in bulk lipid transfer between membranes and intracellular vesicle trafficking. We describe the case of a 37-year-old woman with gait instability, semi-flexed legs, and involuntary distal muscle movements. Genetic testing was performed using next-generation sequencing (NGS), followed by molecular analysis. Fibroblasts from the patient, her mother, and a healthy control were analyzed by immunofluorescence and Western blotting. NGS identified a novel homozygous 2.8 kb deletion encompassing exons 69-70 (69-70del) of the VPS13A gene (NM_033305.3). The same variant was detected in the patient's mother in a heterozygous state and her brother in a homozygous state. Although other deletions in the gene have been described, a comprehensive search of population variant databases and the existing literature did not reveal previous reports of this deletion. Fibroblasts from the patient, her mother and a healthy control were characterized. Functional assays showed a complete absence of the VPS13A protein in the patient's fibroblasts. This study expands the mutational spectrum of VPS13A-linked VPS13A disease and underlines the importance of comprehensive genetic analysis in atypical cases.

Chorein is an endoplasmic reticulum protein expressed in many cell types. Loss-of-function mutations of the gene encoding chorein (VPS13A) are the cause of chorea-acanthocytosis, a rare and severe neurodegenerative disease with chorea-like movements, loss of mental function, progressive muscle weakness and misshaped erythrocytes (acanthocytes). Chorein regulates diverse cellular functions including the cytoskeleton, apoptosis, Ca2+ entry, or autophagy. Since its role in bone is enigmatic, we aimed to explore the function of chorein in osteoblasts. To this end, we generated UMR-106 osteoblast-like cells with stable chorein knockdown (KD) using a CRISPR/Cas9-based approach and compared them to cells undergoing CRISPR/Cas9 with a non-targeting sequence (NT). Gene expression was assessed by qPCR and protein by Western blotting and ELISA. Gene and protein expression of chorein and fibroblast growth factor 23 (FGF23), an osteoblast-derived hormonal regulator of phosphate metabolism, were decreased in KD compared to NT cells. Moreover, FGF23 regulator Phex was down- and Galnt3 was up-regulated in KD compared to NT cells. The expression of further genes regulating osteoblast and osteoclast differentiation was affected by chorein knockdown. Taken together, chorein is expressed in UMR-106 osteoblasts and modulates the expression of various genes affecting osteoblast and osteoclast differentiation and function.

Background: The long-term clinical and laboratory results of a 33-year follow-up of a Greek family with abetalipoproteinemia (ABL) are described. Case Report: The patients (two brothers and their sister, aged 57, 49, and 62 years, respectively) are still alive, being under close surveillance. In two of the three patients, diarrhea appeared in early infancy, while in the third, it appeared during adolescence. CNS symptomatology worsened after the second decade of life. At the same time, night blindness appeared in the advanced stages of the disease, resulting in almost complete loss of vision in one of the male patients and severe impairment in the other. The diagnosis was based on the clinical picture, ophthalmological findings, serum lipid estimations, and presence of peripheral acanthocytosis. All patients exhibited typical serum lipidemic profile, ophthalmological findings, and acanthocytes in the peripheral blood. During the follow-up period, strict dietary modifications were applied, including the substitution of fat with medium-chain triglycerides (MCT oil). After 33 years since the initial diagnosis, all patients are alive without any sign of liver dysfunction despite continuous use of MCT oil. However, symptoms from the central nervous system and vision impairment worsened. Conclusion: The course of these patients suggests that the application of a modified diet, including MCT oil, along with close surveillance, could prolong the survival of patients without significant side effects from the liver.