Mayer-Rokitansky-Kuster-Hauser Syndrome Type II with Fused Kidneys in Pelvic Cavity: A Case Report.

ABSTRACT: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) also known as Müllerian agenesis, is caused by embryologic underdevelopment of the Mullerian duct, with resultant agenesis or atresia of the vagina, uterus, or both. Patients usually present with primary amenorrhea with normal growth and pubertal development. Here we present a case of a 29-year-old woman presented with primary amenorrhea. Secondary sexual characteristics and hormone evaluation were normal. Ultrasound and MRI were conducted and revealed complete absence of uterus, small vaginal canal. Bilateral renal fossa were empty and both the kidneys were located in the pelvic cavity fused to one-another with single renal pelvis giving pancake appearance.

A Unique Clinical Presentation of Congenital Thumb Aplasia, Radioulnar Synostosis, and Chiari Malformation: A Potential Pediatric Syndromic Association.

The medical literature does not currently report a case of co-occurring congenital thumb aplasia, radioulnar synostosis (RUS), and Chiari malformation with scoliosis. Furthermore, there is an overlap of clinical features with other documented syndromes and associations that have potential cardiac, gastrointestinal, hematologic, and nephrological implications, thus contributing to increased morbidity and mortality if left undetected. We describe an interesting case of congenital thumb aplasia, RUS, and Chiari malformation with scoliosis in the absence of non-musculoskeletal abnormalities. These findings prompted further investigation to determine whether this is a unique presentation of a previously described syndrome, due to teratogenic exposure in utero, or a syndromic association yet to be adequately identified by the scientific community. We also identified several candidate genes that may guide genetic testing in the future.

Optimizing sacral screw fixation in patients with caudal regression syndrome.

PURPOSE: The aim of this study is to evaluate and compare techniques and outcomes associated with two different technique of pelvic screw insertion in patients with caudal spine absence. METHODS: A cohort of patients with varying degrees of caudal structural regression, serves as the focal point of this investigation. Pelvic configurations were classified based on established criteria to facilitate comparative analysis. Each patient underwent spinal surgical interventions, with a follow-up period extending beyond 2 years. The primary surgical interventions predominantly involved spinal stabilization coupled with correction of scoliosis and kyphosis through one or two pairs of pelvic screws. RESULTS: In this study, we investigated a cohort of 22 patients with caudal spine absence, encompassing diverse conditions, such as lumbo-sacral aplasia, hemisacrum, and lumbar absence, with preserved sacrum. Following spinal surgery, notable improvements were observed in scoliosis and pathological lumbar kyphosis, with several patients achieving significant functional milestones such as independent ambulation. There were no significant differences in short-term complications between patients undergoing single versus double pair pelvic screw implantation. Long-term complications, primarily non-fusion, were notably more prevalent in patients undergoing fixation with a single pair of pelvic screws. CONCLUSION: Surgical intervention, particularly spinopelvic fixation, demonstrated promising outcomes in terms of improving spinal deformities. The implantation of two pairs of pelvic screws demonstrates greater reliability compared to the insertion of a single pair, diminishing the risk of non-fusion.

Challenges and recent advances in erythropoietin stability.

Erythropoietin (EPO) is a pivotal hormone that regulates red blood cell production, predominantly synthesized by the kidneys and also produced by the liver. Since the introduction of recombinant human EPO (rh-EPO) in 1989 through recombinant DNA technology, the therapeutic landscape for anemia has been improved. rh-EPO's market expansion has been substantial, with its application extending across various conditions such as chronic kidney disease, cancer-related anemia, and other disorders. Despite its success, significant concerns remain regarding the stability of EPO, which is critical for preserving its biological activity and ensuring therapeutic efficacy under diverse environmental conditions. Instability issues, including degradation and loss of biological activity, challenge both drug development and treatment outcomes. Factors contributing to EPO instability include temperature fluctuations, light exposure, and interactions with other substances. To overcome these challenges, pharmaceutical research has focused on developing innovative strategies such as stabilizing agents, advanced formulation techniques, and optimized storage conditions. This review article explores the multifaceted aspects of EPO stability, examining the impact of instability on clinical efficacy and drug development. It also provides a comprehensive review of current stabilization strategies, including the use of excipients, lyophilization, and novel delivery systems.

First Reported Case of Pure Red Cell Aplasia Related to Sotorasib.

We herein report a 64-year-old man with KRASG12C-mutated advanced lung adenocarcinoma previously treated with immune checkpoint inhibitors (ICIs). One month after starting second-line sotorasib treatment, the patient experienced a progressive decline in serum hemoglobin levels. Anemia was accompanied by markedly elevated serum erythropoietin levels and decreased reticulocyte levels. Bone marrow aspiration revealed pure red cell aplasia. No secondary causes other than medication use were identified. Suspected causative drugs were sotorasib and ICIs. Discontinuation of sotorasib for one week improved his anemia; therefore, the causative drug was identified as sotorasib.

A Case Report on Aplasia Cutis Congenita: Insights Into the Impact of Maternal Carbimazole Use.

Congenital aplasia cutis (CAC) is a rare neonatal condition characterized by the absence of skin at birth, often associated with diverse underlying conditions. We report the case of a newborn male admitted on the second day of life with a skin defect on the anterior abdominal wall and a lesion on the left thigh. The mother was treated with carbimazole for hyperthyroidism. Notably, there were no similar cases in the family history. The patient showed favorable progress and normal development following a successful dermo-epidermal allograft. Particular attention was given to managing the risk of infection and ensuring optimal healing through tailored wound care protocols. This case underscores the complexity of CAC, highlighting the importance of early diagnosis, multidisciplinary care, and ongoing research to understand better and effectively treat this rare condition.

Pure Red Cell Aplasia in a Patient with Thymic Hyperplasia, Hypogammaglobulinemia and Adult T-cell Leukemia/Lymphoma.

Acquired pure red cell aplasia (PRCA), caused by thymic hyperplasia, is extremely rare. We herein report a previously healthy 41-year-old man who presented with severe anemia, lymphadenopathy, an upper mediastinal mass, and hypogammaglobulinemia. The patient was eventually diagnosed with PRCA and adult T-cell leukemia/lymphoma (ATLL). The mediastinal mass was pathologically diagnosed as thymic hyperplasia without clear ATLL invasion. Although his anemia improved rapidly after thymectomy, PRCA recurred approximately 500 days later and was accompanied by ATLL exacerbation. The findings in this patient suggest that the Good's syndrome-like symptoms (thymic hyperplasia and hypogammaglobulinemia) in this patient and PRCA may have been paraneoplastic syndromes caused by ATLL.

Comprehensive management of Mayer-Rokitansky-Küster-Hauser syndrome management: A case report.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian aplasia, is a congenital condition characterized by uterine and upper vaginal aplasia. It affects females with a normal female karyotype and typical secondary sex characteristics. The aim of this case report was to highlight the multidisciplinary management approach for MRKH syndrome, focusing on tailored interventions to address physical and psychological challenges and improve reproductive prospects. A 26-year-old married female presented to Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, Wardha, India, in January 2023 with primary amenorrhea. Physical examination revealed a blind vagina and a hypoplastic uterus, indicative of MRKH syndrome. Further evaluation, including pelvic magnetic resonance imaging (MRI), confirmed Müllerian duct abnormalities and bilateral ovarian anomalies. The absence of a functional vagina significantly impacted the patient's quality of life, leading to difficulties with sexual intercourse and emotional distress related to infertility. A collaborative approach involving a gynecologist and a psychiatrist at AVBRH was initiated to address these challenges. The patient underwent vaginoplasty to create a neovagina, enhancing the sexual function and intimate relationship with the spouse. However, due to the hypoplastic uterus, achieving motherhood through traditional means was not possible. Therefore, assisted reproductive techniques, in particular surrogacy, were explored. Normal, functional ovaries were harvested from the patient for use in surrogacy procedures. This comprehensive management strategy exemplifies the challenges associated with MRKH syndrome and underscores the importance of tailored interventions and long-term follow-up. The case highlights the significance of collaborative care in improving the quality of life and reproductive prospects for individuals with MRKH syndrome.

Aplasia cutis congenita of the trunk in a newborn: a rare case report.

Aplasia cutis congenita (ACC) is a rare congenital disorder defined as a congenital skin defect, characterized by the absence of all skin layers at birth. The most frequent presentation is a small erythematous ulcerated or scar-like alopecic ectodermal lesion on the scalp vertex. However, extensive cutis aplasia of the trunk is extremely uncommon. Clinical and radiological evaluation defined the appropriate treatment. We herein report a rare case of a large aplasia cutis congenita of the trunk occurring in a male newborn managed with sulfadiazine silver 1% dressing, complete healing was achieved in about a month. The report highlights that conservative treatment is a highly effective and practical option for managing non-scalp extensive ACC.

[Acquired bone marrow aplasia in children and young adults under the age of 30: Experience of the Pediatric Hematology and Oncology Department of the 20 August Hospital, Casablanca]. / Aplasie médullaire acquise de l'enfant et de l'adulte jeune de moins de trente ans : expérience du service d'hématologie et d'oncologie pédiatrique de l'hôpital 20 Août de Casablanca.

Bone marrow aplasia is a rare and serious hematologic disorder. Although benign, it is a hematologic disorder whose prognosis can be poor and whose spontaneous development can be fatal. Treatment is long, difficult and costly. In developing countries, the mortality rate is high due to the difficulties of therapeutic management, both supportive and specific. We conducted a retrospective study of 92 cases of AM identified in the Pediatric Hematology and Oncology Department of the 20 Août University Hospital in Casablanca over a 10-year period (January 2010-January 2020). In this work, we present an overview of the situation and highlight the difficulties encountered in the management of AM in the Pediatric Hematology and Oncology Department of the University Hospital of Casablanca. In our study, the mean age was 19 years, ranging from 3 months to 29 years, with a peak in the 15-20 age group. The sex ratio (M/F) was 2.06, with a male predominance of 67%. In our series, only 35% of patients had complete bone marrow failure. An anemic syndrome was present in 92% of patients, and hemorrhagic and infectious syndromes were present in 70% and 41% of patients, respectively. The median time from diagnosis to treatment was 82 days. According to the Camitta score, 31% of our patients had mild AM, 41% had severe AM, and 28% had very severe AM. After etiologic evaluation, we concluded that 90% of the patients had idiopathic bone marrow aplasia, 2% had constitutional bone marrow aplasia, and 8% of the patients were suspected to have secondary bone marrow aplasia: post-hepatitis (3 cases), toxic (2 cases), drug-induced (1 case), and aplastic PNH (1 case). Mortality in the first three months after diagnosis was 21%. Sixty-nine percent of our patients received specific treatment: 28 were treated with cyclosporin (CIS) alone as first-line therapy, 20 received a combination of antilymphocyte serum (ALS) and cyclosporin, 2 received hematopoietic stem cell transplantation (HSCT), while 3 were treated with androgens alone. The overall response rate was 30% with CIS, 42% with ALS+CIS and 100% with HSCT. In our study, the overall death rate was 44%, while the one-year survival rate was 40%. It is important to note that septic shock was the leading cause of death (53% of deaths), followed by hemorrhagic shock (24%). This highlights the lack of hemodynamic resuscitation and symptomatic treatment. Our multivariate study defined the following risk factors as predictive of worse survival: age greater than 16 years (RR: 3.28; CI: 1.29-8.33; P=0.012), PNN less than 200 or very severe bone marrow aplasia (RR: 3.01; 1.1-8.08; P=0.028), and failure to receive any specific treatment (RR: 4.07; 1.77-9.35; P=0.0003). The high overall mortality in our series was due to several factors: inaccessibility to effective therapies, delayed diagnosis, failure to initiate specific treatment, inadequate symptomatic treatment, and geographical and financial inaccessibility.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Mayer-Rokitansky-Küster-Hauser Syndrome: A Case Report.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is described in females with a 46, XX karyotype and normal development of secondary sexual characteristics. The primary sexual characteristics are depicted by the congenital aplasia of the uterus and the upper two-thirds of the vagina. Based on the extent of malformations and association of extra-genital anomalies, it is categorized into type I and type II MRKH. The associated malformations seen include skeletal anomalies, renal anomalies, hearing defects, and, rarely, digital and cardiac anomalies. Herewith, we report a case of a two-year-old patient with urogenital anomalies on the left side diagnosed by imaging studies, which were suggestive of MRKH type II. For any child with urogenital anomalies with associated renal, skeletal, and hearing defects, we must suspect MRKH syndrome. The early detection of such anomalies will help in genetic counseling, management of fertility outcomes, and appropriate surgical management.

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system.

GREB1-like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7-year-old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease-causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

Effective treatment of refractory monoclonal gammopathy-associated pure red cell aplasia with isatuximab, pomalidomide and dexamethasone.

Monoclonal gammopathy-associated pure red cell aplasia (MG-PRCA) is characterized by the absence or pronounced hypoplasia of erythroid precursors in the bone marrow, causing reticulocytopenia and a normocytic, normochromic anaemia in a patient with a monoclonal plasma cell dyscrasia. We report here on the successful treatment of MG-PRCA with isatuximab, pomalidomide, and dexamethasone after multiple lines of immunosuppressive and anti-plasma cell-directed treatments.

Use of IV immunoglobulin to treat steroid resistant, immune checkpoint inhibitor-induced pure red cell aplasia: A case report.

Pure red cell aplasia (PRCA) is characterised by normocytic normochromic anaemia, reticulocytopenia and reduced erythroid precursors in bone marrow. PRCA as an immune-related adverse event secondary to immune checkpoint inhibitor (ICI) therapy is rare. Steroids are usually used first line to treat ICI-induced PRCA. Here, we report a case of ICI-induced PRCA with no response to steroids but where intravenous (IV) immunoglobulin was successfully used second line. ICI therapy was reinitiated following PRCA resolution. PRCA recurrence did not occur.

A Case of Oral Lichen Planus Preceding the Diagnosis of Good Syndrome.

Good syndrome (GS) is a rare condition characterized by thymoma and immune deficiency with a poorly understood mechanism in which patients have reduced immunoglobulin levels and circulating B-cells along with impaired T-cell function. GS is often accompanied by autoimmune and inflammatory conditions, and in this report, we present a case of refractory oral lichen planus (OLP) preceding the diagnosis of GS. In this case, a patient with a history of OLP was diagnosed with GS and common variable immunodeficiency (CVID) following thymectomy and was treated with intravenous immunoglobin (IVIG). Additionally, he was found to have pure red cell aplasia managed with cyclosporine. His oral symptoms worsened, and he presented to dermatology. Treatment was initiated with topical clobetasol and tacrolimus for his OLP, and fluconazole was started for concomitant oral candidiasis. His OLP has remained under satisfactory control with this regimen; however, he requires close surveillance for malignancy given his increased risk of oral squamous cell carcinoma (OSCC) with immunosuppression and active OLP. Although rare, clinicians should be aware of GS and its association with erosive OLP along with the heightened risk of infection in these patients.

A Case of Fibular Aplasia-Tibial Campomelia-Oligosyndactyly (FATCO) Syndrome Associated With Split Hand/Foot Syndrome With Long Bone Deficiency (SHFLD) and Review of the Literature.

Split hand/foot malformation is a heterogeneous congenital disorder mainly presented with a median cleft of hands or/and feet. It can be associated with long bone aplasia, a syndrome also known as split hand/foot syndrome with long bone deficiency (SHFLD), which is a very rare condition. We report a very rare case of a male fetus with SHFLD syndrome combined with fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO) syndrome. FATCO syndrome is also an extremely infrequent congenital limb defect by itself. Based on our review of the literature, there appears to be no other FATCO case reported in Greece.

Deficiency of Adenosine Deaminase 2

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessively inherited autoinflammatory disorder caused by loss-of-function mutations in the ADA2 gene. Although the pathogenesis involves the triggering of a proinflammatory cascade due to increased production of inflammatory cytokines such as tumor necrosis factor (TNF)-α and dysregulation of neutrophil extracellular trap formation resulting from an excess accumulation of extracellular adenosine, the pathogenetic mechanism still needs further clarification due to the broad clinical spectrum. In addition to the initially described vasculitis-related symptoms, hematological, immunological, and autoinflammatory symptoms are now well recognized. The diagnosis is made by demonstration of pathogenic variants of ADA2 with biallelic loss of function and identification of low plasma ADA2 catalytic activity. Currently, TNF-α inhibitors are the treatment of choice for controlling vasculitis manifestations and preventing strokes. However, in patients presenting with severe hematologic findings, TNF-α inhibitors are not the treatment of choice and hematopoietic stem cell transplantation has been shown to be successful in selected cases. Recombinant ADA2 protein and gene therapy are promising treatment modalities for the future. In conclusion, ADA2 deficiency has a broad phenotype and should be considered in the differential diagnosis of different clinical situations. In this review, we summarize the disease manifestations of ADA2 deficiency and available treatment options.