Spectrum of Inpatient Pediatric Dermatology Cases at a Tertiary Health Care Centre in South India.

Background Dermatologists and pediatricians commonly encounter pediatric dermatology cases in their clinical practice, and the number has risen for the past decade. While numerous studies have addressed adult inpatient dermatology cases, there is a lack of data on the same for the pediatric population. Aim The study aimed to investigate the spectrum and outcomes of inpatient pediatric dermatology cases at a tertiary health care center. Methods This was a hospital-based, cross-sectional study that included children under the age of 16 years with primary skin disorders who were admitted to the pediatric dermatology unit. Patients were categorized into six groups based on their provisional diagnosis for better analysis. Results A total of 105 children were admitted, with a male-to-female ratio of 1.2:1. The average age of admitted children was 5.8 years, with the majority belonging to the school-going age group, accounting for 44% of the patients. Conclusion Inflammatory skin conditions like childhood psoriasis and erythroderma were the most common group of disorders presented to us, followed by hereditary conditions like keratinization disorders and mechanobullous disorders. Pediatric dermatology emergencies (PDEs) require an inter-professional approach for timely intervention and management.

Systemic autoinflammatory disease, IgA glomerulonephritis and renal cortical necrosis: coincidence or causation?

We present a patient with a rare systemic autoinflammatory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in extremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymphadenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and proteinuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclophosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid progression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenomenon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.

Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Mevalonato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenomegalia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias mostrando nefropatía por IgA alternando actividad y cronicidad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatillos para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para generar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

Congenital absence of touch does not preclude normal cognitive and socioemotional development.

Attachment theory holds that development of normal affective and social behavior requires physical contact between infant and caregiver. The elevation of touch to paramount importance has gone unchallenged because, prior to the present study, no individual with a congenital lack of somatosensation has been reported, much less studied for psychosocial development. Here we describe Kim, who since birth, has been unable to perceive touch, temperature changes, or pain on the body surface. Despite her inability to sense physical contact, Kim has above-average intelligence. She functions normally in social situations with a variety of people, recognizing emotions in herself and others and demonstrating appropriate affect. Kim experiences anxiety that appears grounded in realistic fears and uncertainties particular to her somatic insensitivity, thus serving as adaptive vigilance in reaction to an abnormal sensorium. Her normal socioemotional development, evident from an early age, likely resulted from Kim being able to appreciate her parents' loving care through gaze, movement, and hearing. In sum, Kim upends the idea of touch as critical to developing a sense of self, secure attachment, and family bonds.

Assessment the carrier frequency of monogenic diseases in populations requiring assisted reproductive technology.

PURPOSE: The objective of this study is to assess the carrier frequency and pathogenic variation of monogenetic diseases in a population of 114 subjects in Han Chinese from Hebei province who are undergoing assisted reproductive technology through the utilization of Expanded Carrier Screening (ECS). METHODS: The study utilized a panel consisting of 155 severe monogenic recessive genetic diseases for ECS. Next-generation sequencing technology was employed to identify specific variants associated with ECS in a cohort of 114 subjects from 97 couples, comprising 97 females and 17 male spouses. RESULTS: A total of 114 individuals received ECS. The carrier rate of pathogenic genes in the enrolled population was 44.74% (51/114). Among the 97 females, the carrier rate of pathogenic genes was higher in those without assisted reproduction indicators than in those with assisted reproduction indicators (59.09% vs. 41.33%). However, the carrier rate of pathogenic genes in males without assisted reproductive technology was slightly lower than that with assisted reproductive technology (40% vs. 41.67%). Among both female and male participants, the carrier rate of pathogenic genes between individuals without indicators of assisted reproduction and those with such indicators was 55.55% vs. 41.38%. In 51 carriers, 72.55% (37/51) carried one genetic variant, 25.49% (13/51) carried two genetic variants, and 1.96% (1/51) carried three genetic variants. A total of 38 pathogenic genes were detected in this study, and GJB2 and MMACHC were most common. The carrier rates of the two genes were both 5.26% (6/114). A total of 55 variations were detected, and c.235delC was most frequently found. The carrier rate was 3.51% (4/114). The incidence of couples carrying the same pathogenic genes was 1.03% (1/97). CONCLUSIONS: The findings elucidate the carrier rate of pathogenic genes among 155 severe monogenic recessive genetic diseases and underscore the significance of ECS as a preventive measure against congenital anomalies. When both partners carry the same genetic mutation for a monogenic disease, preventive strategies can be taken in offspring through preimplantation genetic testing (PGT), prenatal genetic testing, or the utilization of donor gametes. ECS is instrumental in assessing reproductive risk, guiding fertility-related decisions, and reducing the prevalence of monogenic recessive genetic disorders in subsequent generations.

Characteristics of arthritis in patients with familial Mediterranean fever.

BACKGROUND: Many of the familial Mediterranean fever (FMF) patients present with arthritis during attacks, which may vary in its characteristics. AIMS: In this study, we aimed to describe and characterise arthritis in FMF patients. METHODS: We used our hospital's record system to retrospectively identify FMF patients with arthritis who presented to our clinic between 2005 and 2020. The prevalence, laboratory results of attack, remission periods, genetic mutations, demographic data, characteristics of attacks, characteristics of arthritis, comorbidities, treatments and treatment responses were recorded. RESULTS: Nine hundred fifty-four patients from a cohort of 2350 FMF patients had arthritis (40%). The male/female ratio was 0.49 in patients with arthritis. The frequency of at least one exon 10 mutation was high. The age of onset of symptoms was earlier for patients with arthritis. Monoarticular pattern was more frequent compared to oligo- and polyarticular patterns. Colchicine resistance was higher; the required colchicine dose for disease control and the frequency of use of biological agents were higher compared to general FMF population. CONCLUSION: Since M694V mutation is common and the colchicine dose required for disease control is high, we can conclude that the disease activity is high in FMF patients with arthritis. The frequency of sacroiliitis and spondyloarthropathy is significantly increased, especially in individuals with M694V mutation, suggesting that there may be a common pathway in their pathogenesis. FMF should be included in the differential diagnosis in patients presenting with arthritis in FMF endemic regions.

A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer.

BACKGROUND: Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. METHODS: Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. RESULTS: The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss-of-heterozygosity of the wild-type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. CONCLUSION: Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.

Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report.

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.

Unveiling the genetic landscape of hereditary melanoma: From susceptibility to surveillance.

The multifactorial etiology underlying melanoma development involves an array of genetic, phenotypic, and environmental factors. Genetic predisposition for melanoma is further influenced by the complex interplay between high-, medium-, and low-penetrance genes, each contributing to varying degrees of susceptibility. Within this network, high-penetrance genes, including CDKN2A, CDK4, BAP1, and POT1, are linked to a pronounced risk for disease, whereas medium- and low-penetrance genes, such as MC1R, MITF, and others, contribute only moderately to melanoma risk. Notably, these genetic factors not only heighten the risk of melanoma but may also increase susceptibility towards internal malignancies, such as pancreatic cancer, renal cell cancer, or neural tumors. Genetic testing and counseling hold paramount importance in the clinical context of suspected hereditary melanoma, facilitating risk assessment, personalized surveillance strategies, and informed decision-making. As our understanding of the genomic landscape deepens, this review paper aims to comprehensively summarize the genetic underpinnings of hereditary melanoma, as well as current screening and management strategies for the disease.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Hereditary Antithrombin Deficiency Pilot Project Registry from the American Thrombosis and Hemostasis Network (ATHN).

BACKGROUND: Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). ATHN 12: HAD Pilot Project established a registry to collect data on patients with HAD to inform current practice and serve as a platform to design a multicenter global registry for patients with HAD. METHODS: The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and AT concentrate administration were recorded. RESULTS: Ninety-four (94) patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD18); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% patients: (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low molecular weight heparin was administered in 33% and AT concentrate in 19% and 11% prior and post-delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular, respectively. Overall, 35% participants received AT concentrate without adverse events. CONCLUSIONS: In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend towards using DOACs. LMWH was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.

Emerging therapies in hereditary ataxias.

Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.

Validation and correlations of the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT) in Chinese patients with angioedema.

Background: The impact of recurrent angioedema can be severely debilitating and remains difficult to quantify. Several standardized patient-reported outcome measures (PROMs), including the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT), have been developed and translated into different languages. However, these PROMs have yet to be validated in Chinese individuals, and their correlations in the Chinese population remain unknown. Objective: Our aim was to validate the Chinese versions of the AAS, AE-QoL questionnaire, and AECT and assess their intercorrelations. Methods: A prospective cohort of 118 Chinese patients with recurrent angioedema at the Angioedema and Urticaria Centre of Reference and Excellence in Hong Kong completed the traditional Chinese versions of the AAS, AE-QoL questionnaire, and AECT. We analyzed the reliability and validity of these PROMs and their correlations with each other as well as with generic PROMs. Results: The Chinese AAS, AE-QoL questionnaire, and AECT demonstrated excellent internal consistency (Cronbach α = 0.920, 0.976, and 0.832, respectively; McDonald ω = 0.972, 0.977, and 0.901, respectively). Confirmatory factor analysis for the AE-QoL questionnaire showed an acceptable fit with the 4-dimensional model (comparative fit index = 0.869; Tucker-Lewis index = 0.842). The AECT showed significant correlations with both the AAS and AE-QoL questionnaire (ρ = -0.750 and -0.456 respectively [both P < .05]). The AE-QoL questionnaire was moderately correlated with certain domains of generic PROMs such as the Work Productivity and Activity Impairment Questionnaire: General Health, version 2.0, and the Short Form 12-Item Health Survey, version 2 (all ρ < 0.60). Conclusion: The Chinese AE-QoL questionnaire, AAS, and AECT are valid and reliable tools for use with Chinese patients. More validated tools should be made available to improve patient care and research for all patients with angioedema globally.

Hereditary transthyretin amyloidosis with hydrocephalus at 27 years old: A case report.

Hereditary transthyretin amyloidosis is autosomal dominant and results from mutations in the transthyretin gene. The Val30Met variant is the most common genetic mutation, although mutations vary within populations. More than 150 mutations in transthyretin have been reported; however, the Leu111Glu (p. Leu131Glu) mutation has been reported to date. We report the case of a 32-year-old Japanese male with a history of cerebral hemorrhage and hydrocephalus at age 27 years. The patient was referred to our department after his sibling had been diagnosed with hereditary transthyretin amyloidosis. Twelve-lead electrocardiography exhibited poor R progression, and transthoracic echocardiography showed normal findings. 99mTc-labelled pyrophosphate scintigraphy showed high accumulation in the heart. Histological tests using a right ventricular endomyocardial biopsy showed amyloid deposits and immunostaining only for transthyretin. Genetic analysis confirmed a novel missense variant, Leu111Glu, on the transthyretin gene. We diagnosed the patient with hereditary transthyretin amyloidosis, and the patient received genetic counseling. Patients with hereditary transthyretin amyloidosis carrying the Leu111Gln variant may present as a patient with a hydrocephalus-dominant phenotype. To the best of our knowledge, this is the first case report of the transthyretin Leu111Glu variant. Learning objective: Hereditary transthyretin amyloidosis with the Leu111Gln variant has not been previously reported in Japan. While cardiac involvement progresses without overt abnormal findings on electrocardiogram and echocardiogram, 99mTc-labelled pyrophosphate scintigraphy can be a useful tool for the early diagnosis of hereditary transthyretin amyloidosis. This mutation may result in a predominantly hydrocephalus phenotype, and organ damage is expected to progress rapidly. Therefore, early diagnosis and appropriate treatment are necessary.

Young-Onset Rectal Cancer: Is It for Real?

The incidence of early-onset colorectal cancer has been rising over the last two decades. Tumors in young patients have distinct features compared to older patients. They predominantly arise in the distal colon and rectum and have poor histological features. Patients tend to present at a more advanced stage and be exposed to more aggressive management approaches; however, this has not translated into a significant survival benefit compared to their older counterparts. This chapter will share current evidence on risk factors and management options for early onset colorectal cancer with a focus on rectal cancer.

A Rare Case of Iron Overload in Hereditary Spherocytosis: A Case Report.

Hereditary spherocytosis (HS) is a hereditary hematologic disorder characterized by fragile spherical red blood cells that are susceptible to hemolysis. HS patients are often asymptomatic or present with anemia; however, serious complications of chronic hemolysis can include cholelithiasis and aplastic crisis. Splenectomy is considered the standard surgical treatment in moderate and severe forms of HS, with the main complication being a life-long risk of infection. Interestingly, our case suggests a possibility of secondary hemochromatosis as a complication of chronic hemolysis seen in HS. A vast majority of hemochromatosis patients possess a genetic predisposition, which increases their serum iron level and iron storage within the reticuloendothelial system. However, we present a case in which the genetic panel for common mutations associated with hemochromatosis resulted as negative. This case emphasizes the need for increased awareness regarding the potential development of idiopathic hemochromatosis in patients with long-standing HS, allowing for prompt intervention and preventing the associated complications.

Pure Hereditary Spastic Paraplegia in a Patient With a Novel Heterozygous KIDINS220 Gene Mutation.

This case presents a somewhat unique and different phenotype of hereditary spastic paraplegia from previously reported kinase D-interacting substrate of 220 kDa (KIDINS220) gene mutation-related disease. We report a unique putative causative heterozygous mutation in KIDINS220 in a pure hereditary spastic paraplegia (HSP) patient expanding the HSP group further. We also deliberate on how our case was different from prior KIDINS220-related pathologies including spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, and the observation of KIDINS220 and aquaporin-4 (AQP4) downregulation in the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. These findings warrant further investigations of the biology of KIDINS220. With the advent of new gene editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), variants such as ours provide an opportunity for targeted precision medicine.

A Rare Case of Multiple Bone Infarctions and Abnormal Pulmonary Function Tests in a Patient With Compound Heterozygous Hemoglobin S and Type 2 Hereditary Persistence of Fetal Hemoglobin.

Sickle cell disease (SCD) is a group of inherited blood disorders characterized by abnormal hemoglobin production, affecting individuals worldwide with varying prevalence across different populations. Manifestations vary, ranging from severe to mild. SCD is characterized by the presence of hemoglobin S (HbS), which distorts erythrocytes upon deoxygenation, leading to sickling. This results in hemolytic anemia, painful vaso-occlusive crises (VOC), and multiple organ damage, including bones, due to microinfarcts. Sickle cell trait (SCT), or carrier status, is not considered an SCD and often runs a benign course. We report a 44-year-old man of African descent presenting with a one-month history of pain in his ankles and feet. He had a prior diagnosis of sickle cell "trait" without previous VOC. Hematological indices were normal. Hemoglobin electrophoresis showed absent HbA, elevated HbS, elevated HbF, and normal HbA2. X-rays and MRI revealed bilateral bone infarction in diaphyses of right proximal and bilateral distal tibias. Molecular analysis of [Formula: see text]-globin revealed compound heterozygous hemoglobin S and type 2 deletion of persistence of fetal hemoglobin (HPFH). Pulmonary function tests revealed restrictive lung disease. A literature review from 1946 to May 2024 via PubMed, EMBASE, and Medline was performed, revealing two cases of HbS-HPFH with avascular necrosis affecting the femoral neck were briefly reported more than 60 years ago. Although pulmonary function tests in SCD typically show a mild restrictive pattern with decreased diffusion capacity and rarely an obstructive pattern, no cases of HbS-HPFH were identified. In conclusion, multiple bone infarctions are extremely rare in HbS-HPFH. Lung and bone diseases might be unrecognized in this unique disorder.

The Genetic Diagnostics of Hemochromatosis: Disparities in Low- Versus High-Income Countries.

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study.

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.