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Clinical Immunology (Orlando, Fla.) Oct 2023Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who...
Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34 cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.
Topics: Humans; Paired Box Transcription Factors; Phenotype; T-Lymphocytes; Thymus Gland; Severe Combined Immunodeficiency
PubMed: 37689091
DOI: 10.1016/j.clim.2023.109757 -
SAGE Open Medical Case Reports 2023Brain calcifications, previously known as Fahr's disease, is a rare neurological disorder marked by various clinical symptoms, including movement disorders, cognitive...
Brain calcifications, previously known as Fahr's disease, is a rare neurological disorder marked by various clinical symptoms, including movement disorders, cognitive impairment, and psychiatric disturbances. Despite its clinical importance, its pathophysiology is unclear and there are no specific treatments. We present four cases of brain calcifications from our tertiary care center, with three female patients (75%) and an average age of 63 years. Our cohort featured both genetic and endocrine etiologies, including one primary familial brain calcification case with a c.852del frameshift mutation in the gene, and two endocrinopathy-related cases. One patient had an acute stroke which may have been contributed by brain calcifications. Computerized tomography and magnetic resonance imaging scans revealed basal ganglia and dentate nucleus calcifications. Treatment involved physical and occupational therapy in all patients. Hypoparathyroidism-related brain calcifications were treated with oral supplementation with calcitriol, calcium, and vitamin D. Three patients showed improvement or stability of their symptoms. This case series underscores the diverse clinical presentations and etiologies of brain calcifications. The complex pathophysiology involves disrupted Ca-PO homeostasis, deficient cellular PO transport, and vascular irregularities in genetic etiologies. Future research should focus on identifying novel genetic mutations, understanding molecular pathways, and refining diagnostic techniques. Integrating multidisciplinary approaches may improve diagnosis, management, and prognosis for patients with this intricate neurological disorder.
PubMed: 37663154
DOI: 10.1177/2050313X231197521 -
European Thyroid Journal Dec 2023Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed...
OBJECTIVE
Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed symptom-based treatment algorithm including a protocolized attempt to phase out supplementation.
METHODS
In a prospective multicenter study, patients were treated according to the new algorithm and compared to a historical cohort of patients treated with a biochemically based approach. The primary outcome was the proportion of patients receiving calcium and/or alfacalcidol supplementation. Secondary outcomes were calcium-related complications and predictors for supplementation.
RESULTS
One hundred thirty-four patients were included prospectively, and compared to 392 historical patients. The new algorithm significantly reduced the proportion of patients treated with calcium and/or alfacalcidol during the first postoperative year (odds ratio (OR): 0.36 (95% CI: 0.23-0.54), P < 0.001), and persistently at 12 months follow-up (OR: 0.51 (95% CI: 0.28-0.90), P < 0.05). No severe calcium-related complications occurred, even though calcium-related visits to the emergency department and readmissions increased (OR: 11.5 (95% CI: 4.51-29.3), P <0.001) and (OR: 3.46 (95% CI: 1.58-7.57), P < 0.05), respectively. The proportional change in pre- to postoperative parathyroid hormone (PTH) was an independent predictor for supplementation (OR: 1.04 (95% CI: 1.02-1.07), P < 0.05).
CONCLUSIONS
Symptom-based management of postthyroidectomy hypocalcemia and a protocolized attempt to phase out supplementation safely reduced the proportion of patients receiving supplementation, although the number of calcium-related hospital visits increased. For the future, we envision a more individualized treatment approach for patients at risk for delayed symptomatic hypocalcemia, including the proportional change in pre- to post- operative PTH.
Topics: Humans; Calcium; Hypocalcemia; Thyroid Gland; Prospective Studies; Thyroidectomy; Parathyroid Hormone; Calcium, Dietary; Algorithms
PubMed: 37655701
DOI: 10.1530/ETJ-23-0044 -
Frontiers in Endocrinology 2023The chromosome 22q11.2 deletion syndrome comprises phenotypically similar diseases characterized by abnormal development of the third and fourth branchial arches,...
INTRODUCTION
The chromosome 22q11.2 deletion syndrome comprises phenotypically similar diseases characterized by abnormal development of the third and fourth branchial arches, resulting in variable combinations of congenital heart defects, dysmorphisms, hypocalcemia, palatal dysfunction, developmental or neuropsychiatric disorders, and impairment of the immune system due to thymic dysfunction. Other genetic syndromes, often called DiGeorge-like, share clinical and immunological features with 22q11.2 deletion syndrome. This syndrome has been rarely associated with malignancies, mainly hematological but also hepatic, renal, and cerebral. Rarely, malignancies in the head and neck region have been described, although no aggregate of data on the development of thyroid neoplasms in patients with this clinical phenotype has been conducted so far.
MATERIALS AND METHODS
To characterize this possible association, a multicenter survey was made. Thus, we present a case series of five pediatric patients with 22q11.2 deletion syndrome or DiGeorge-like syndrome who were occasionally found with confirmed or highly suspected neoplasms of the thyroid gland during their follow-up. In three cases, malignancies were histologically confirmed, but their outcome was good due to an early recognition of suspicious nodules and precocious surgery.
CONCLUSIONS
This study underlines for clinicians the higher risk of neoplasms in the head and neck district for patients affected by these syndromes. It also emphasizes the importance of a prolonged clinical and ultrasound follow-up for patients with this clinical and immunological phenotype.
Topics: Humans; DiGeorge Syndrome; Follow-Up Studies; Thyroid Neoplasms; Neck
PubMed: 37635986
DOI: 10.3389/fendo.2023.1209577 -
The Journal of International Medical... Aug 2023Idiopathic hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia secondary to inadequate parathyroid hormone secretion. Hypocalcemia-related...
Idiopathic hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia secondary to inadequate parathyroid hormone secretion. Hypocalcemia-related cataract is most often observed in patients with postoperative hypoparathyroidism, whereas primary hypoparathyroidism-related cataract is rare and displays slow progression. Cataract usually occurs in people aged 18 to 50 years. Here, we describe a 17-year-old boy with bilateral cataract and a history of hypocalcemic tetany who was diagnosed with idiopathic hypoparathyroidism. Phacoemulsification with implantation of a monofocal aspherical intraocular lens was performed in the right eye; 6 months later, it was performed in the left eye. Elevated phosphorus and diminished calcium were observed in blood and aqueous humor. A deep anterior chamber, relatively thin central corneal thickness, large white-to-white distance, and thin lens were also observed. During follow-up, neither eye displayed intraocular lens decentration; best-corrected visual acuity was 20/20 in both eyes. These findings suggest that ophthalmologists should be vigilant when hypocalcemic tetany and cataract are present, especially in adolescents and young adults.
Topics: Male; Young Adult; Humans; Adolescent; Tetany; Hypocalcemia; Cataract; Hypoparathyroidism; Eye
PubMed: 37622441
DOI: 10.1177/03000605231193820 -
Molecular Psychiatry Oct 202322q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread...
22q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterization of white matter microstructure in participants with 22q11.2DS (12-15 years) and those undergoing typical development (8-18 years) using a customized magnetic resonance imaging scanner which is sensitive to axonal morphology. A rich array of diffusion MRI metrics are extracted to present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences in individuals with 22q11.2DS. A recent, large-scale consortium study of 22q11.2DS identified higher diffusion anisotropy and reduced overall diffusion mobility of water as hallmark microstructural alterations of white matter in individuals across a wide age range (6-52 years). We observed similar findings across the white matter tracts included in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that abnormal microstructural connectivity in 22q11.2DS may be mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo white matter phenotype of 22q11.2DS, and promote the continued investigation of shared features in neurodevelopmental and psychiatric disorders.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; DiGeorge Syndrome; White Matter; Diffusion Tensor Imaging; Brain; Schizophrenia
PubMed: 37495890
DOI: 10.1038/s41380-023-02178-w -
Endocrine Connections Sep 2023Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their...
OBJECTIVE
Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves' disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves' disease.
DESIGN
Retrospective cohort study from a single institution.
METHODS
We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves' disease.
RESULTS
We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012-2014 to 6% in 2020-2021. For patients with Graves' disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015-2016 to 2% (1 out of 56) in 2020-2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012-2014 to 10% (10 out of 51) in 2020-2021.
CONCLUSION
Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.
SIGNIFICANCE STATEMENT
Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves' disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.
PubMed: 37487033
DOI: 10.1530/EC-23-0198 -
The Journal of Surgical Research Aug 2023We sought to investigate the association of concurrent parathyroidectomy (PTX) with risks of total thyroidectomy (TTX) through analysis of Collaborative Endocrine...
INTRODUCTION
We sought to investigate the association of concurrent parathyroidectomy (PTX) with risks of total thyroidectomy (TTX) through analysis of Collaborative Endocrine Surgery Quality Improvement Program data. TTXis a common operation with complications including recurrent laryngeal nerve injury, neck hematoma, and hypoparathyroidism. A subset of patients undergoing thyroidectomy undergoes planned concurrent PTX for treatment of primary hyperparathyroidism. There are limited data on the risk profile of TTX with concurrent PTX (TTX + PTX).
METHODS
We queried the Collaborative Endocrine Surgery Quality Improvement Program database for patients who underwent TTX or TTX + PTX from January 2014 through April 2020. Multivariable logistic regression was performed to predict hypoparathyroidism, vocal cord dysfunction, neck hematoma, and postoperative emergency department visit. Covariates included patient demographics, patient body mass index, indication for surgery, central neck dissection, anticoagulation use, and surgeon volume.
RESULTS
Thirteen thousand six hundred forty seven patients underwent TTX and 654 patients underwent TTX + PTX. Unadjusted rates of hypoparathyroidism were higher in TTX + PTX patients at 30 d (9.6% versus 7.4%, P = 0.04) and 6 mo (7.9% versus 3.1%, P < 0.001). On multivariable regression, TTX + PTX was associated with an increased risk of hypoparathyroidism at 30 d (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.57-2.79) and 6 mo (OR 4.63, 95% CI 3.06-7.00) and an increased risk of postoperative emergency department visit (OR 1.66, 95% CI 1.20-2.31). TTX + PTX was not associated with recurrent laryngeal nerve injury or neck hematoma.
CONCLUSIONS
Concurrent PTX in patients undergoing TTX is associated with increased risk of immediate and long-term hypoparathyroidism, which should be considered in informed consent discussions and operative decision-making.
Topics: Humans; Parathyroidectomy; Thyroidectomy; Recurrent Laryngeal Nerve Injuries; Hypoparathyroidism; Hematoma; Postoperative Complications; Retrospective Studies
PubMed: 37043874
DOI: 10.1016/j.jss.2023.02.036