Identifying a Gene Deficiency in the Antiviral Innate Immune Signaling Pathway.

Innate immunity is an important defense barrier for the human body. After viral pathogen-associated molecular patterns (PAMPs) are detected by host-pathogen recognition receptors (PRRs), the associated signaling pathways trigger the activation of the interferon (IFN) regulatory factor (IRF) family members and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, any gene defects among the signaling adaptors will compromise innate immune efficiency. Therefore, investigating genetic defects in the antiviral innate immune signaling pathway is important. We summarize the commonly used research methods related to antiviral immune gene defects and outline the relevant research protocols, which will help investigators study antiviral innate immunity.

The influence of color vision deficiency on vessel visibility during colorectal endoscopic submucosal dissection and the potential advantage of red dichromatic imaging to achieve color vision barrier-free.

Objectives: Although color information is important in gastrointestinal endoscopy, there are limited studies on how endoscopic images are viewed by people with color vision deficiency. We aimed to investigate the differences in the visibility of blood vessels during endoscopic submucosal dissection (ESD) among people with different color vision characteristics and to examine the effect of red dichromatic imaging (RDI) on blood vessel visibility. Methods: Seventy-seven pairs of endoscopic images of white light imaging (WLI) and RDI of the same site were obtained during colorectal ESD. The original images were set as type C (WLI-C and RDI-C), a common color vision. These images were computationally converted to simulate images perceived by people with color vision deficiency protanope (Type P) or deutanope (Type D) and denoted as WLI-P and RDI-P or WLI-D and RDI-D. Blood vessels and background submucosa that needed to be identified during ESD were selected in each image, and the color differences between these two objects were measured using the color difference (ΔE 00) to assess the visibility of blood vessels. Results: ΔE 00 between a blood vessel and the submucosa was greater under RDI (RDI-C/P/D: 24.05 ± 0.64/22.85 ± 0.66/22.61 ± 0.64) than under WLI (WLI-C/P/D: 22.26 ± 0.60/5.19 ± 0.30/8.62 ± 0.42), regardless of color vision characteristics. This improvement was more pronounced in Type P and Type D and approached Type C in RDI. Conclusions: Color vision characteristics affect the visibility of blood vessels during ESD, and RDI improves blood vessel visibility regardless of color vision characteristics.

Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Rare presentations of small bowel endometriosis.

Despite endometriosis being a relatively common chronic gynecological condition in women of childbearing age, small bowel endometriosis is rare. Presentations can vary from completely asymptomatic to reported symptoms of abdominal pain, bloating, and diarrhea. The following two cases depict very atypical manifestations of ileal endometriosis that presented as obscure intermittent gastrointestinal bleeding and bowel obstruction requiring surgical intervention. The first case describes a previously healthy 40-year-old woman with severe symptomatic iron deficiency anemia and intermittent melena. A small bowel enteroscopy diagnosed multiple ulcerated strictures in the distal small bowel as the likely culprit. Despite nonsteroidal anti-inflammatory drug-induced enteropathy being initially considered as the likely etiology, histopathological examination of the resected distal ileal segment revealed evidence of endometriosis. The second case describes a 66-year-old with a presumptive diagnosis of Crohn's disease who reported a 10-year history of intermittent perimenstrual abdominal pain, diarrhea, and nausea with vomiting. Following two subsequent episodes of acute bowel obstruction and surgical resection of the patient's stricturing terminal ileal disease, histopathological examination demonstrated active chronic inflammation with endometriosis. Small bowel endometriosis should be considered as an unusual differential diagnosis in women who may present with obscure gastrointestinal bleeding from the small bowel or recurrent bowel obstruction.

Prevalencia de hipertirotropinemia neonatal comoindicador de deficiencia de yodo en la provincia de La Pampa: un análisis epidemiológico / Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis

Introducción. El yodo desempeña un rol fundamental en el metabolismo, el crecimiento y el desarrollo humano. Durante el embarazo y la infancia, la demanda de este micronutriente aumenta considerablemente. La tirotropinemia neonatal (TSHn) aumentada, definida como TSHn ≥5 mUI/l, es un marcador que señala la deficiencia de yodo en una población cuando su prevalencia supera el 3 %. Objetivo. Determinar la prevalencia de TSHn ≥ 5 en La Pampa durante el período 2021-2022, analizar su correlación con diferentes variables y compararla con datos de una cohorte histórica. Población y métodos. Estudio transversal, de diseño descriptivo-analítico, sobre una población de neonatos nacidos en las cinco zonas sanitarias de la provincia de La Pampa durante los años 2021 y 2022. Resultados. De los 5778 neonatos evaluados, el 9,6 % presentó niveles de TSHn ≥5 mUI/l. El 70,4 % de estas mediciones fueron realizadas después del tercer día de vida. No se observaron diferencias significativas en la frecuencia de niveles elevados de TSHn según el año de nacimiento, peso al nacer o días hasta la extracción. Se registró una mayor prevalencia en el sexo masculino (10,6 % versus 8,5 %; p = 0,007) y entre los neonatos nacidos a término (9,8 % versus 6,6 %; p = 0,02). La prevalencia de hipertirotropinemia fue superior a la observada en una cohorte de 2001-2002. Conclusiones. La prevalencia de hipertirotropinemia neonatal en La Pampa durante los años 2021 y 2022 fue del 9,6 %, lo que indica un estado de deficiencia leve de yodo en la provincia, superior al reportado hace dos décadas.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIUL, are a marker of iodine deficiency in a population if its prevalence is higher than 3%.Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021­2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort.Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of  the  5778  assessed  newborn  infants,  9.6%  had  nTSH  levels  ≥  5  mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until samplecollection.A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001­2002 cohort. Conclusions. The  prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what  had been reported 2 decades ago.

Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study.

BACKGROUND: α1-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α1-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. METHODS: In a nationwide nested study, we identified 2702 individuals with α1-antitrypsin deficiency and 26,750 control subjects without α1-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. RESULTS: Individuals with α1-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81-2.63), leukemia (1.76, 1.12-2.79), liver cancer (3.91, 2.23-6.85), and cancer overall (1.25, 1.13-1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55-3.58), 1.83 (1.19-2.81), 4.46 (2.74-7.28), and 1.45 (1.31-1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60-4.95) and skin disease (2.93, 2.19-3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α1-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α1-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). CONCLUSION: Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.

A Curious Case of Severe Recurrent Hypocalcemia.

Hypocalcemia, characterized by low blood calcium levels, can range from asymptomatic to life-threatening. Common causes include hypoparathyroidism and vitamin D deficiency (VDD). Pseudohypoparathyroidism is a rare metabolic disorder marked by resistance to parathyroid hormone (PTH). This report details a young female presenting with severe hypocalcemia, hyperphosphatemia, and elevated PTH levels. She also had an associated VDD, which complicated the clinical picture. Despite receiving intravenous calcium and oral supplementation, she required extended treatment and readmission. Genetic testing revealed a variant in the CACNA1S gene. Her condition eventually stabilized with a strict, adjusted treatment regimen. This case underscores the importance of a systematic diagnostic approach, prolonged intravenous calcium therapy, and close monitoring. Pseudohypoparathyroidism represents a rare cause of severe hypocalcemia, emphasizing the need for close monitoring and regular follow-up to achieve improved outcomes.

Role of iron deficiency anemia in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a relapsing chronic inflammatory disorder of the small and large gut with rising incidence and prevalence worldwide. Iron deficiency anemia is one of the most common extraintestinal manifestations of IBD, which correlates with the disease activity and tendency to relapse even after successful management. Anemia affects various aspects of quality of life, such as physical, cognitive, emotional, and workability, as well as healthcare costs. The anemia in IBD can be due to iron deficiency (ID) or chronic disease. The relative frequency of ID in IBD is 60%, according to some studies, and only 14% receive treatment. The evaluation of ID is also tricky as ferritin, being an inflammatory marker, also rises in chronic inflammatory diseases like IBD. The review of anemia in IBD patients involves other investigations like transferrin saturation and exploration of other nutritional deficiencies to curb the marker asthenia with which these patients often present. It underscores the importance of timely investigation and treatment to prevent long-term sequelae. We can start oral iron therapy in certain circumstances. Still, as inflammation of the gut hampers iron absorption, an alternative route to bypass the inflamed gut is usually recommended to avoid the requirement for blood transfusions.

Vitamin D-dependent Rickets Type 1A Mimicking Pseudohypoparathyroidism in Presence of Active Tuberculosis.

Vitamin D-dependent rickets type 1A is caused by pathogenic variants of CYP27B1 gene, which is inherited in autosomal recessive pattern. These variants lead to defective 1α-hydroxylase enzymatic activity, leading to impaired renal formation of 1,25(OH)2 vitamin D. We report a case of a 16-year-old Asian male patient, with short stature and progressive bone deformity, whose biochemical parameters revealed low levels of 1,25(OH)2 vitamin D, low serum calcium levels, along with high phosphorus and raised levels of intact parathyroid hormone. These biochemical parameters suggested the diagnosis of pseudohypoparathyroidism. The patient also had concurrent extrapulmonary tuberculosis during the time of presentation to our endocrine unit. However, on molecular testing, it was revealed that the patient was harboring pathogenic variants of the CYP27B1 gene, in a compound heterozygous manner, with a novel missense mutation in exon 6 of the CYP27B1 gene, c.1136G > C (p.Arg379Thr), suggesting the diagnosis of vitamin D-dependent rickets type 1A. The cause of high phosphorus at the time of presentation, which led to a diagnostic dilemma of pseudohypoparathyroidism, was later explained by presence of active extra pulmonary tuberculosis. This report describes a case of vitamin D-dependent rickets type 1A, mimicking pseudohypoparathyroidism owing to presence of concurrent illness like extrapulmonary tuberculosis.

Acquired factor XIII deficiency presenting with multiple intracranial hemorrhages and right hip hematoma: A case report.

BACKGROUND: Factor XIII (FXIII) deficiency is a rare yet profound coagulopathy. FXIII plays a pivotal role in hemostasis, and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging. Immunological assays for detecting FXIII inhibitors are indispensable for diagnosing acquired FXIII deficiency; however, the availability of suitable testing facilities is limited, resulting in prolonged turnaround times for these assays. CASE SUMMARY: In this case study, a 53-year-old male devoid of significant medical history presented with recurrent intracranial hemorrhages and a hematoma in the right hip. Subsequent genetic analysis revealed a homozygous mutation in the ACE gene, confirming the diagnosis of acquired FXIII deficiency. CONCLUSION: This case underscores the significance of considering acquired deficiencies in clotting factors when evaluating patients with unexplained bleeding episodes.

Positive impact of sunlight exposure on mental health in a naval population.

Naval shipboard operations impose numerous environmental and occupational stressors, which can adversely affect mental and physical health outcomes. Moreover, this operational setting also complicates the implementation of countermeasures to protect personnel from these stressors. Thus, any easily accessible or modifiable protective factors should be explored further for their potential to support the health of military personnel. Daily sunlight exposure is one such factor that has demonstrated positive effects on health outcomes. For the current study, sunlight exposure and self-reported health outcomes were explored in a large population of U.S. Navy personnel (N > 11,000). Mediator analyses examined the relationship between mental and physical health while controlling for key confounding variables such as morale and exercise. Although the overall regression models indicated only a slight impact on physical health, sunlight exposure had a significant direct effect on mental health even while controlling for the mediating influence of morale. Sunlight exposure also had an impact on morale and an indirect influence on mental health through morale. Additional analyses further supported the possible mental health benefits of sunlight exposure even while accounting for occupational differences. The results suggest that prescribed sunlight exposure aboard ships could be used to promote positive mental health during naval operations.

Alpha-1 Antitrypsin Deficiency in a Young Never Smoker With Novel Pi*Null Homozygous Mutation: a Case Report.

Alpha-1 antitrypsin deficiency is an autosomal codominant disorder caused by SERPINA1 gene mutations. PI*Z and PI*S mutations commonly underlie this deficiency, but rarer homozygous PI*null (Q0) mutations may result in a complete loss of alpha-1 antitrypsin (AAT). Such rare mutations lead to severe AAT deficiency and early onset of lung disease. We present a case of 35-year-old female never-smoker born to consanguineous parents who developed severe panlobular emphysema and end-stage respiratory insufficiency requiring lung transplantation. Subsequent genetic testing identified her as homozygous for a novel c.82del mutation - here named Q0Bani-Yas based on the region of the primary carrier's origin - which resulted in undetectable levels of alpha-1 antitrypsin protein.

Angioedema due to acquired C1-inhibitor deficiency associated with monoclonal gammopathies of undetermined significance.

BACKGROUND: No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet. OBJECTIVE: Describe the biological and clinical characteristics, evolution and response to treatment of MGUS-associated AAE-C1-INH. MATERIAL AND METHODS: We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period. RESULTS: Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11 and IgA in 6 patients. Mean age at first angioedema attack was 63 years (SD = 13) and at diagnosis 66 years (SD = 11). 88 % of patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. 50 % of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of which 60% had an undetectable serum monoclonal immunoglobulin. CONCLUSION: Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attacks frequency increases.

Thiamine deficiency as a differential diagnosis for severe fatigue in terminally ill cancer patients.

OBJECTIVES: Patients with advanced cancer present various symptoms as their disease progresses. Among these, fatigue is a frequent symptom in patients with advanced cancer and is associated with decreased quality of life (QOL). However, there are few reports regarding its association with thiamine deficiency (TD). METHODS: We report a case in which we found TD in a patient with advanced lung cancer who presented with weight loss, significant fatigue, and appeared to have a worsening general condition, for whom symptoms were dramatically improved within a short period of time by intravenous administration of thiamine. RESULTS: The patient was a 76-year-old woman who had been diagnosed with lung cancer and liver metastases 6 months earlier. Due to interstitial pneumonia, she was not a candidate for chemotherapy and so palliative care was started. At 8 months after initial diagnosis, the patient complained of fatigue during a medical examination, so a blood sample was taken. A week later, she visited the hospital with a cane. She felt extremely fatigued and was unable to stand, but results from the previous blood test revealed that a TD. The fatigue disappeared 15 minutes after intravenous administration of thiamine and she was able to return home without the cane. SIGNIFICANCE OF RESULTS: Fatigue is a frequent symptom in advanced cancer patients, and TD may be the underlying cause. Inclusion of TD in the differential diagnosis may contribute to improving patient QOL.

Isolated Adrenocorticotropic Hormone Deficiency Presenting With Arthritis: A Case Report.

This case report describes a case of isolated adrenocorticotropic hormone (ACTH) deficiency that presented with arthritis. Initial investigations, including blood tests, imaging, and musculoskeletal ultrasonography, did not confirm to any specific connective tissue disease, making it initially difficult to identify the cause of the arthritis. Subsequent adrenal crisis led to the diagnosis of isolated ACTH deficiency through comprehensive endocrine evaluation. The patient's musculoskeletal symptoms were resolved following corticosteroid replacement therapy together with generalized symptoms. This report highlights isolated ACTH deficiency as a rare but one of the causes of polyarticular joint pain and underscores the importance of considering endocrine disorders in the differential diagnosis of unexplained arthritis, particularly when accompanied by systemic symptoms.

Clinical characteristics and treatment during preconception and perinatal period of infertile women with non-classical 21-hydroxylase deficiency.

OBJECTIVE: A single-center observational study to determine the clinical characteristics and therapeutic dose adjustments in women of reproductive age with infertility and non-classical 21-hydroxylase deficiency (NC-21OHD). DESIGN: A retrospective analysis of 20 women of reproductive age who were diagnosed with NC-21OHD during an infertility evaluation at Shengjing Hospital of China Medical University from January 2013 to May 2024 was performed. The clinical manifestations, auxiliary examinations, adjustment of glucocorticoid (GC) treatment during preconception and perinatal period, and pregnancy outcomes were analyzed. RESULTS: 14 of 16 patients (87.5%) had inappropriately elevated progesterone levels during the follicular phase. The average levels of 17α-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate in the follicular phase were also significantly increased. All 20 infertile patients received GC treatment before preparing for pregnancy. During the follow-up, six of 20 patients had seven conceptions. three patients had spontaneous abortions in the first trimester and four patients delivered babies (4/20). Three patients had a GC dose that was maintained throughout pregnancy and one had an increase in the GC dose starting in the second trimester. Of the remaining 16 patients, seven are still trying to conceive and nine had discontinued treatment. CONCLUSIONS: An abnormal increase in the follicular phase progesterone level is the most common serologic marker for NC-21OHD among infertile women. Ovulation can be restored after GC treatment, but the proportion of successful conceptions remains low. The dose of GCs in most pregnant women remained unchanged throughout pregnancy.

Diagnostic options, physiopathology, risk factors and genetic causes of permanent congenital hypothyroidism: A narrative review.

Background: In Permanent congenital hypothyroidism (PCH) is a lifelong condition characterized by a deficiency in thyroid hormone, leading to various neurodevelopmental complications. Early clinical signs are often nonspecific and easily overlooked, but newborn screening programs have improved early detection. Methods: This narrative review aims to provide insights comparatively transient and permanent PCH and also the diagnosis, risk factors, underlying pathophysiology, and genetic causes associated with PCH. Relevant studies were identified through a comprehensive search using the term 'Permanent congenital hypothyroidism' (Mesh) across scientific databases of electronic databases such as PubMed, Scopus, and Web of Science. Results: Prompt initiation of thyroid hormone replacement therapy, particularly within the initial two weeks postpartum, crucially enhances neurocognitive development outcomes. Multiple predictive approaches, encompassing screening TSH levels, maternal thyroid history, and levothyroxine dosage per kilogram assessment, aid in identifying PCH. Recent studies have demonstrated a mounting prevalence of PCH, contributing significantly to the overall rise in CH incidence. Genetic factors, primarily DUOX2 and DUOXA2 mutations, alongside environmental influences such as post-term birth, low birth weight, and macrosomia, may induce PCH. Nonetheless, reliable markers for early PCH prediction upon diagnosis remain elusive, leading to delayed recognition post-ceasing levothyroxine treatment around age 3. Conclusions: Recent studies have observed an increased incidence of PCH, contributing substantially to the overall rise in cases of congenital hypothyroidism. Understanding the diagnostic options and genetic etiologies associated with PCH is crucial for the early identification and appropriate management.

Poly(Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibitors in the Treatment of Advanced Ovarian Cancer: A Narrative Review.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have appeared as a revolutionary approach to treating advanced ovarian cancer, particularly in patients with breast cancer (BRCA) mutations and homologous recombination deficiency (HRD). This narrative review explores PARP inhibitors' clinical efficiency, safety, and changing role in this context. PARP inhibitors, such as olaparib, niraparib, or rucaparib, provide considerable benefits regarding progression-free survival expansion and overall outcomes improvement in first-line maintenance and recurrent settings. The underlying mechanisms, patient selection criteria, and resistance patterns are discussed, alongside insights into combination therapies to overcome resistance and enhance therapeutic efficacy. Ongoing clinical trials and future potential for personalized therapy approaches using PARP inhibitors for advanced ovarian cancer are also highlighted. However, despite these drugs' phenomenal ability to revolutionize treatment protocols for such cancer types, several challenges remain: toxicity management, cost, and development of resistance will require more research to optimize their use or broaden patient populations who can benefit from them.

Periodic Paralysis in a Child With Thermosensitive Mitochondrial Trifunctional Protein Deficiency.

Mitochondrial trifunctional protein (MTP) deficiency is a fatty acid oxidation disorder associated with a spectrum of phenotypes. Patients with high residual enzyme activity tend to have milder phenotypes, and recently, fever-induced episodic myopathy was reported in association with a thermosensitive form of MTP deficiency. We report a 10-year-old male with recurrent episodes of acute flaccid paralysis involving upper and lower extremities in association with bulbar muscle weakness in the context of febrile illness, a phenotype reminiscent of recurrent periodic paralysis. The episodes started at the age of 3 years and have always been followed by full recovery within 1-2 weeks with no residual weakness. Whole exome sequencing revealed a homozygous c.2132C > T, p.(Pro711Leu) variant in HADHA. The variant leads to mildly reduced long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain ketoacyl-CoA thiolase (LCKAT) enzyme activities and reduced MTP protein expression in patient's fibroblasts when cultured at 37°C. Enzyme activities and MTP protein expression diminished when fibroblasts were cultured at 40°C. This is the first published report of confirmed recurrent periodic paralysis as a manifestation of a thermosensitive form of MTP deficiency, and it calls for this condition to be considered when evaluating patients with recurrent periodic paralysis given therapeutic implications.

Gly183Ser homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Brazilian patient: case report.

OBJECTIVES: Steroid 5α-reductase type 2 deficiency (5α-RD2) is an autosomal recessive disorder caused by mutations in the SRD5A2 gene. This condition is characterized by reduced enzymatic activity of the 5α-reductase type 2 enzyme. Individuals with mutations in the SRD5A2 gene may exhibit various symptoms of under-masculinization in 46, XY individuals. We conducted a comprehensive analysis of the SRD5A2 gene in a patient with disorder of sex development (DSD). CASE PRESENTATION: We describe a patient with a homozygous Gly183Ser variant in the SRD5A2 gene. Their sibling also carries this variant in homozygosity, while both parents have it in a heterozygous state. The patient presents with predominantly female traits and was raised as a girl. Although the siblings exhibit distinct phenotypic characteristics, both have assumed a male gender identity. CONCLUSIONS: This study reveals different phenotypes for the two siblings, highlighting the complexity of establishing a genotype-phenotype correlation in the SRD5A2 gene. It is noteworthy that the Gly183Ser variant seems to be more prevalent among individuals of African descent, aligning with our patient's ethnic background.