Transcobalamin deficiency - a rare genetic defect in transportation of cobalamin; case report.

BACKGROUND: Vitamin B12 is primarily transported from plasma to cells by Transcobalamin. Deficiency of Transcobalamin is a rare autosomal recessive disorder that results in unavailability of cobalamin in cells and accumulation of homocysteine and methylmalonic acid. CASE REPORT: We report a case of a 2-year-old male child with persistent pancytopenia, recurrent infections, and megaloblastic anemia. Next-generation sequencing identified a novel variant in exon 8 of TCN2 gene. Substantial improvement has been observed following administration of high doses of parenteral methylcobalamin. CONCLUSION: In patients with unresolved pancytopenia and megaloblastic anemia, Transcobalamin deficiency should be investigated and treated promptly to prevent any irreversible and harmful outcome.

Contemplating dengue: the thinker's reflection on symptoms.

In this image, the autors reinterprate "The Thinker" from Auguste Rodin to transfer knowledge about dengue fever, which can range from flu-like illness to severe hemorrhagic fever. By fostering awareness and understanding of dengue fever, we strive to empower individuals and communities in the ongoing fight against dengue and other infectious threats.

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report.

BACKGROUND: Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. CASE PRESENTATION: We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. CONCLUSIONS: Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Management of granulomatosis with polyangiitis complicated by intestinal perforation and pancytopenia: a case report and literature review.

Granulomatosis with polyangiitis is a systemic vasculitis. While the classic triad typically comprises otorhinolaryngologic, pulmonary, and renal manifestations, it is essential to recognize that granulomatosis with polyangiitis can affect any organ. Furthermore, reports have documented less common sites of involvement, such as the gastrointestinal tract. In this case-based review, we focus on a case of granulomatosis with polyangiitis presenting with intestinal perforation and the added challenge of concurrent pancytopenia.A 25-year-old female was diagnosed with granulomatosis with polyangiitis, with her clinical course progressing from joint pain to severe multi-organ involvement, including gastrointestinal complications. Treatment challenges emerged with the development of pancytopenia. While this may not directly result from granulomatosis with polyangiitis, it introduced an additional layer of complexity and delayed the induction of remission with immunosuppressants. Despite initial stabilization, an unexpected jejunal perforation occurred, requiring surgical intervention and subsequent postoperative care. The case underscores the complex nature of granulomatosis with polyangiitis and its potential complications. A literature search yielded discrete relevant cases in the context of our patient's intricate presentation, which has been summarized.We highlight the complexities in diagnosing and managing granulomatosis with polyangiitis-related complications, especially in uncommon presentations, and emphasize the importance of a personalized approach to patient care in these circumstances.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

Perioperative proximal splenic artery embolization in cirrhotic patients with splenomegaly.

INTRODUCTION: The purpose of this study was to determine the effect of proximal splenic artery embolization (SAE) in cirrhotic patients with splenomegaly who underwent surgical laparotomy. MATERIAL AND METHODS: This retrospective observational study included 8 cirrhotic patients with splenomegaly. They underwent proximal SAE before- (n = 6) or after (n = 2) laparotomy. Vascular plugs or coils were placed in the proximal splenic artery. The diameter of the portal vein and the splenic volume were recorded. Clinical outcome assessments included platelet counts, the model for end-stage liver disease (MELD) score, and complications. RESULTS: After embolization, the portal venous diameter was significantly smaller (pre: 13.6 ± 2.7 mm, post: 12.5 ± 2.3 mm, p = 0.023), the splenic volume was significantly decreased (pre: 463.2 ± 145.7 ml, post: 373.3 ± 108.5 ml, p = 0.008) and the platelet count was significantly higher (pre: 69.6 ± 30.8 × 103/µl, post: 86.8 ± 27.7 × 103/µl, p = 0.035). Before embolization, the median MELD score was 12; after embolization, it was 11 (p = 0.026). No patient developed post-treatment complications after embolization. CONCLUSIONS: The reduction of hypersplenism by perioperative proximal SAE may be safe and reduce the surgical risk in cirrhotic patients with splenomegaly.

Gaucher Disease: A First Reported Adult Case in Indonesia.

A 44-year-old female presented with a distended abdomen and fatigue. On physical examination, prominent splenomegaly was found. The laboratory investigations revealed pancytopenia and decreased albumin-globulin ratio. The abdominal ultrasonography revealed splenomegaly, cholelithiasis, and cystitis, and the bone survey showed osteopenia. Differential diagnoses included leukemia, multiple myeloma, and myelofibrosis therefore bone marrow puncture was performed. However, histopathologic examination found Gaucher-like cells in the bone marrow aspiration. The finding of CD68 positivity in Gaucher-like cells by using the immunohistochemistry staining supporting Gaucher disease. To confirm the diagnosis, an examination of glucocerebroside substrate from the patient's blood plasma was performed. Glucosylsphingosine, a deacylated form of glucosylceramide, was markedly elevated. Therefore, the diagnosis of Gaucher disease was confirmed. This is the first reported adult Gaucher case diagnosed in Indonesia.

Clinical and biochemical footprints of inherited metabolic disease. XVI. Hematological abnormalities.

Many classical inherited metabolic diseases (IMDs) are associated with significant hematological complications such as anemia or thrombosis. While these may not be the prominent presenting feature of these conditions, management of these issues is important for optimal outcomes in people with IMDs. Some disorders that are included in the nosology of inherited metabolic disorders, such as inherited disorders of red cell energy metabolism, have purely hematological features, and have typically been cared for by a hematologist. In the 16th issue of the Footprints series, we identified 265 IMDs associated with hematological abnormalities. We review the major hematological manifestations of IMDs, suggest further investigation of hematological findings, and discuss treatment options available for specific hematological complications of IMDs.

Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, genetic, autosomal recessive disorder characterized by severe thrombocytopenia, due to inefficient bone marrow megakaryopoiesis eventually leading to aplasia. Majority of the cases are due to homozygous or compound heterozygous mutations in MPL gene encoding for thrombopoietin (THPO) receptor protein. CAMT can be diagnosed at early phase of life, with major complication of transfusion dependency and hematopoietic transplantation as only curative treatment. We have investigated the sequence variations in MPL gene of 7 bone marrow failure (BMF) subjects, who presented with clinically diverse phenotypes, through next generation sequencing (NGS). Plasma THPO levels were estimated using ELISA. Insilico sequence and structure-based analyses were performed to understand the structural and functional implications of mutations, identified through NGS. We studied 7 CAMT subjects suspected of BMF, who presented with severe thrombocytopenia followed by pancytopenia, bleeding manifestation and physical anomalies. The plasma THPO levels were significantly elevated (p<0.05) in all the cases. Molecular analysis by NGS identified 9 genomic mutations in MPL gene. These included 7 non-synonymous substitution, 1 nonsense substitution and 1 in-del mutations, of which 4 are novel mutations. Insilico analysis predicted damaging effects on THPO-R and its reduced affinity for THPO for all the identified mutations. CAMT is a rare disorder with diverse clinical phenotypes and diagnosis is challenging. The elevated plasma THPO levels should be considered for the primary diagnosis and prognosis of the disease. However, molecular analysis of MPL gene is important for the diagnosis and management of the disease through genetic counselling. Though the cytokines, THPO-R agonist are used for the treatment of CAMT, HSCT is the only curative therapy.

Lysinuric protein intolerance presenting as pancytopenia and splenomegaly mimicking acute leukaemia: a case report.

BACKGROUND: Lysinuric protein intolerance is a rare inherited metabolic disease due to autosomal recessive mutations of the SLC7A7 gene. The affected patients commonly present with protein-rich food intolerance, failure to thrive, hepatosplenomegaly, muscle hypotonia and lung involvement due to impaired intestinal absorption and excessive urinary excretion of dibasic amino acids. Presentation with splenomegaly and cytopenia without other features has not been reported. Here we report a Sri Lankan girl with lysinuric protein intolerance presenting with pancytopenia and splenomegaly mimicking acute leukaemia. CASE PRESENTATION: Two years and six months old Sri Lankan girl presented with persistent pancytopenia following a viral illness. She was asymptomatic without vomiting, diarrhoea, abdominal pain or irritability. Physical examination revealed pallor and isolated firm splenomegaly of 2 cm. Growth parameters and other system examinations were normal. Full blood count revealed anaemia, leukopenia and thrombocytopenia. The blood picture showed a mixture of hypochromic microcytic and normochromic normocytic red cells with occasional pencil cells and macrocytes. Bone marrow examination was normal except for occasional megaloblasts; however, serum vitamin B12 and red blood cell folate were normal. The metabolic screen showed a high anion gap compensated metabolic acidosis, high lactate and ketosis. Genetic mutation analysis using whole exome sequencing revealed compound heterozygous variants of the SLC7A7 gene, confirming the diagnosis of lysinuric protein intolerance. CONCLUSION: We report a child with lysinuric protein intolerance presenting with pancytopenia and splenomegaly without other disease features. This case report adds to the heterogenic presentations of lysinuric protein intolerance, which is considered a multifaceted disease.

Trends in clinical features and severity of Plasmodium vivax malaria among children at tertiary care center in North India.

BACKGROUND: Malaria is a significant cause of morbidity and mortality in adults and children. Plasmodium falciparum is the primary cause of severe malaria, but recently Plasmodium vivax is also recognized to cause severe malaria-associated morbidity and mortality. The study focuses on determining the mortality related to severity parameters in individuals under 12 years and their critical presentation in P.vivax malaria-infected children. METHODS: A prospective cross-sectional hospital-based study was conducted at Safdarjung Hospital, New Delhi, and ICMR-NIMR, New Delhi. All clinically suspected cases were admitted for screening. Exclusion criteria (rapid malaria antigen test, microscopy and medication history) were applied to all the admitted patients (n = 221) to obtain P.vivax patients only. Patients aged ≤ 12 years were included in the study. DNA was extracted from dried blood spots and amplified by nested PCR, followed by visualization on gel electrophoresis. RESULT: A total of 221 clinically suspected cases of malaria were screened for P.vivax. After implementing various exclusion criteria, 45/221 cases were enrolled for the study, among which 44.4% (20/45) of children had the symptoms of severe malaria in terms of cerebral malaria, thrombocytopenia, anemia, pancytopenia, acute respiratory distress syndrome and hemophagocytic lymphohistiocytosis. CONCLUSION: Plasmodium vivax mono-infection can cause severe manifestation and must be treated as P.falciparum without any delay because it may lead to increased morbidity and mortality. A changing trend in clinical symptoms has shown in P.vivax which was an earlier phenomenon of P.falciparum.

The journey from viral hepatitis to hypocythemia: Two case reports.

Acute viral hepatitis, including hepatitis A, B, E, D, and G, can lead to severe bone marrow suppression due to cytotoxic lymphocytes. The bone marrow suppression causes aplastic anaemia which is mostly unresponsive to immunosuppressive therapy. Such patients require bone marrow transplant for a complete cure. The pancytopenia can evolve during recovery from transaminitis. We are presenting two case reports relating aplastic anaemia with acute viral hepatitis in two young patients-23 and 16 years of age. The 23-year-old female patient had hepatitis A associated with aplastic anaemia whereas the young 16-year-old male patient was diagnosed with Hepatitis E IgG associated aplastic anaemia. Unfortunately, the first patient could not cope with the complications relating to pancytopenia and was unable to reach the bone marrow transplant stage. The second patient did not have a bone marrow transplant but showed an excellent response to immunosuppressive therapy before the transplant and survived.

Persistent Pancytopenia as a Long-COVID Manifestation in a Patient with Adult-Onset Still's Disease: A Case Report.

Background: Adult-onset Still's disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient's laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man's symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia.

Pancytopenia and thrombosis defects in zebrafish mutants of Fanconi anemia genes.

Progressive pancytopenia is a common feature observed in DNA crosslink repair deficiency disorder, Fanconi anemia (FA). However, this phenotype has not been recapitulated in single FA gene knockout animal models. In this study, we analyzed hematological characteristics in zebrafish null mutants for two FA genes, fanca and fanco. In adult mutants, we demonstrate age-associated reduction in blood cell counts for all lineages, resembling progressive pancytopenia in FA patients. In larval mutants, we demonstrate vascular injury-induced thrombosis defects, particularly upon treatment with crosslinking agent diepoxybutane (DEB), indicating DNA damage induced inefficiency of thrombocytes.

A Case of Chronic Lymphocytic Leukemia Complicated by Hemophagocytic Lymphohistiocytosis: Identifying the Aberrant Immune Response.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may complicate hematologic malignancies. HLH and malignancies have common clinical features, and HLH diagnostic criteria (HLH-2004/Hscore) were not validated in this specific population. We describe a case of a 72-year-old patient with a history of chronic lymphocytic leukemia stable for over 10 years who presented with fever and cytopenia. After excluding infectious etiologies and the progression of her disease, HLH was diagnosed. The patient was treated with etoposide, dexamethasone, intravenous immunoglobulin, and rituximab. Despite initial clinical improvement, the patient deteriorated and developed pulmonary aspergillosis and CNS involvement that reflected uncontrolled HLH. The patient died 45 days after her presentation. An unusual feature of this case was that HLH was not triggered by infection, disease transformation, or treatment. This case emphasizes the challenges of differentiating the development of overwhelming HLH from other complications associated with hematologic malignancy.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report.

The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.

[Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with methotrexate and etanercept]. / Imitation eines Felty-Syndroms durch eine viszerale Leishmaniasis bei rheumatoider Arthritis unter Therapie mit Methotrexat und Etanercept.

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF­α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.

When refeeding is not enough: severe and prolonged pancytopenia in an adolescent with anorexia nervosa.

A 15-year-old female patient with anorexia nervosa presented an unusually prolonged and severe episode of pancytopenia with severe thrombopenia and severe leucopenia. Despite effective refeeding, active specialized interventions were necessary. Upon admission, the patient presented with severe and symptomatic thrombopenia, severe neutropenia and gelatinous marrow transformation. In addition to refeeding, active interventions such as platelet transfusion and granulocyte-colony stimulating factor were successful to manage the patient's complications. The etiological search for pancytopenia was negative. The patient's prolonged starvation was probably a key factor. Medical history, clinical presentation, evolution, and biological data including bone marrow aspiration results are presented. Management of cytopenia and of their complications in a context of severe starvation is discussed in regard of existing literature. A simple monitoring attitude may prove insufficient in cases of severe pancytopenia in anorexia nervosa.Level of evidence V, descriptive study.

Multi-organ involvement and intratubular calcium phosphate deposition in the kidney biopsy: what should we investigate?

BACKGROUND: Anorexia nervosa is frequently associated with alcohol use disorder. Both of them may adversely affect almost every body system, leading to worse clinical outcomes and high mortality risk. Nonetheless, there is little evidence interrelating anorexia nervosa, alcohol use disorder, and kidney failure. CASE: We report a case of a 30-year-old male with multi-organ involvement at admission, including pancytopenia, electrolyte alterations, impaired liver function, and renal failure. The kidney biopsy revealed calcium phosphate crystalline nephropathy and IgA nephropathy. The bone marrow biopsy and aspiration showed a hypocellular bone marrow and a focal spindle cell infiltrate with atypical vascular proliferation. Nonspecific liver disease was revealed by ultrasound. Further investigation was performed, uncovering a possible masked diagnosis of anorexia nervosa and alcohol use disorder. With the restoration of adequate nutrition and the withdrawal of possible external triggers, a partial recovery was achieved. CONCLUSIONS: Anorexia nervosa and alcohol use disorder may promote tissue injury, including kidney failure, specifically calcium phosphate crystalline nephropathy and IgA nephropathy. This multi-organ involvement may lose its reversibility if anorexia nervosa and alcohol use disorder remain persistent. An early diagnosis and a successful multidisciplinary approach may prevent life-threatening complications. LEVEL OF EVIDENCE: Level V, case report.