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Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference population, represent a diverse group due to multiple underlying causes of reduced growth. This classification results in a heterogeneous patient cohort. SGA children are prone to endocrinological and metabolic issues not only in childhood but also extending into adolescence and adulthood. This population faces elevated health risks, including persistent short stature, premature adrenarche, pubertal development alterations, neurocognitive problems, and metabolic syndrome. Insulin resistance emerges as a pivotal factor c nht6j7ikontributing to these metabolic complications, prominently featuring obesity, insulin resistance, hypertension, and an increased risk of type 2 diabetes mellitus in adulthood. These medium- to long-term complications significantly impact their quality of life. Growth hormone (GH) therapy for short children born SGA facilitates height normalization throughout childhood, adolescence, and into adulthood. Catch-up growth, however, correlates with heightened risks of obesity, insulin resistance, and metabolic syndrome. Conversely, those without catch-up growth tend to exhibit pronounced short stature and cognitive dysfunction. Given these determinants, comprehensive management and clinical monitoring of SGA children should commence in the neonatal period and extend into adulthood. Recognizing and addressing these challenges early in life can mitigate the long-term impact on health and well-being, emphasizing the importance of a lifelong approach to their care.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Recién Nacido , Niño , Humanos , Adolescente , Adulto , Síndrome Metabólico/complicaciones , Edad Gestacional , Calidad de Vida , Recién Nacido Pequeño para la Edad Gestacional , Obesidad/complicacionesRESUMEN
OBJECTIVE: The management of prediabetes and hyperglycemia is an increasingly important aspect of care in patients with thalassemia. In light of the limited evidence about the management of GD (glucose dysregulation) with glucose-lowering agents (GLAs), we have conducted a retrospective survey in TDT and NTDT patients with diabetes mellitus to collect more detailed information on GLA use in order to make preliminary recommendations. STUDY DESIGN AND METHOD: A questionnaire was prepared and distributed to the tertiary thalassemia care Centers of ICET-A Network. RESULTS: Eight thalassemia care Centers [Bulgaria, Greece, Iran, Italy (4 Centers) and Qatar], following 1.554 with transfusion-dependent thalassemia (TDT), 132 (8.4%) with diabetes and 687 with non-transfusion-dependent thalassemia (NTDT), 27 (3.9%) with diabetes, participated in the retrospective survey. The records of 117 TDT patients and 9 NTDT patients with diabetes treated with GLAs were analyzed. Metformin, a biguanide, was the most frequently used drug (47.6 %), followed by alpha-glucosidase inhibitors (5.5 %), incretins (4.7%) and insulin secretagogues (3.1%). In 68 (61.2) patients GLAs was prescribed as monotherapy, while the remaining 49 (38.8%), who had inadequate glucose control with metformin, were treated with combination treatment. Fifty-one patients of 126 (40.4%) initially treated with oral GLA, for a mean duration of 61.0 ± 35.6 months (range: 12- 120 months), required insulin therapy for better metabolic control. CONCLUSION: This retrospective study covers an unexplored area of research in patients with thalassemia and GD. Oral GLAs appear to be safe and effective for the treatment of diabetes mellitus in patients with thalassemia, and can achieve adequate glycemic control for a substantial period of time.
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Diabetes Mellitus , Metformina , Talasemia , Talasemia beta , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Glucosa , Humanos , Insulina/uso terapéutico , Datos Preliminares , Estudios Retrospectivos , Talasemia/terapiaRESUMEN
Sexual precocity refers to the appearance of physical and hormonal signs of pubertal development at an earlier age. It may be considered as the expression of secondary sexual characteristics prior to the pubertal age In central precocious puberty (CPP), which is gonadotropin-dependent, early maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis occurs, with the full spectrum of physical and hormonal changes of puberty. True precocious puberty in girls must also be distinguished from premature thelarche (PT), usually with breast development before the age of 3 years, and premature pubarche (PA), with the isolated development of pubic hair. These conditions are not usually associated with accelerated growth rate or advancement in bone age. Clinical, laboratory and instrumental evaluations are necessary for the diagnosis. Pelvic ultrasound could serve as a complementary tool for the diagnosis, treatment and follow-up of CPP. The interpretation of clinical, laboratory and strumental data must be performed by an expert pediatric endocrinologist to maximize the diagnostic value in females with pubertal disorders.
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Pubertad Precoz , Niño , Preescolar , Femenino , Humanos , Pubertad , Pubertad Precoz/diagnóstico por imagen , Pubertad Precoz/terapia , UltrasonografíaRESUMEN
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Talasemia beta , Glucosa , Humanos , Prevalencia , Encuestas y Cuestionarios , Talasemia beta/epidemiologíaRESUMEN
Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities.
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ADN Ligasa (ATP)/genética , Enfermedades Gastrointestinales/genética , Motilidad Gastrointestinal/genética , Encefalomiopatías Mitocondriales/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Animales , Femenino , Enfermedades Gastrointestinales/patología , Humanos , Masculino , Encefalomiopatías Mitocondriales/patología , Mutación , Linaje , Pez CebraRESUMEN
Hashimoto encephalopathy (HE) is a rare but controversial entity encompassing a variety of neuropsychological presentations in the setting of autoimmune thyroid disease. HE, mostly described in adults, with a femaletomale ratio of 4:1, is a relatively rare entity in the pediatric population and probably under recognized as a cause of acute encephalopathy in children and adolescents. A number of pathogenetic mechanisms have been suggested. Female prevalence, presence of autoantibodies, fluctuating course, and response to immunomodulatory therapy suggest the autoimmune nature of the disease. Existing diagnostic criteria for adults require modification to be applied to children and adolescents, who differ from adults in their clinical presentations, clinical findings, autoantibody profiles, treatment response, and long-term outcomes. A combination of neurological findings, positive antithyroid autoantibodies, and responsiveness to steroids is diagnostic of HE. We add a new case of HE in an adolescent girl and review the current HE literature.
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Encefalopatías , Encefalitis , Enfermedad de Hashimoto , Adolescente , Autoanticuerpos , Encefalopatías/etiología , Encefalitis/diagnóstico , Femenino , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/tratamiento farmacológico , HumanosRESUMEN
OBJECTIVES: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent ß thalassemia major (TM), ß-thalassemia intermedia (TI) and sickle cell disease (SCD). DESIGN: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. MAIN OUTCOME DATA: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. RESULTS: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). CONCLUSIONS: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID- 19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age.
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not available.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adolescente , COVID-19 , Prueba de COVID-19 , Niño , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Italia/epidemiología , Masculino , Pandemias , Neumonía Viral/diagnóstico , SARS-CoV-2RESUMEN
BACKGROUND: The new Coronavirus identified in Whuan at the end of 2019 (SARS-CoV-2) belongs to the Beta Coronavirus genus and is responsible for the new Coronavirus 2019 pandemia (COVID-19). Infected children may be asymptomatic or present fever, dry cough, fatigue or gastrointestinal symptoms. The CDC recommends that clinicians should decide to test patients based on the presence of signs and symptoms compatible with COVID-19. MATERIAL AND METHODS: 42 children (the majority < 5 years of age) were referred, to our Pediatric Department, as possible cases of COVID-19 infection. Blood analysis, chest X-ray, and naso-oropharyngeal swab specimens for viral identification of COVID-19 were requested. RESULTS: None of the screened children resulted positive for COVID-19 infection. At first presentation, the most frequent signs and symptoms were: fever (71.4%), fatigue (35.7%) and cough (30.9%). An high C-reactive protein value and abnormalities of chest X-ray (bronchial wall thickening) were detected in 26.2% and 19% of patients, respectively. Almost half of patients (45.2%) required hospitalization in our Pediatric Unit and one patient in Intensive Care Unit. CONCLUSIONS: Testing people who meet the COVID-19 suspected case definition criteria is essential for clinical management and outbreak control. Children of all ages can get COVID-19, although they appear to be affected less frequently than adults, as reported in our preliminary survey. Further studies are needed to confirm our observations.
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Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Admisión del Paciente , Neumonía Viral/diagnóstico , Enfermedad Aguda , Adolescente , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/complicaciones , Servicio de Urgencia en Hospital , Femenino , Enfermedades Gastrointestinales/virología , Humanos , Lactante , Recién Nacido , Masculino , Pandemias , Neumonía Viral/complicaciones , SARS-CoV-2 , TriajeRESUMEN
Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the present report reviews briefly the frequency, the major risk factors, and the surveillance of HCC in ß-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy and Greece. Among HCV-infected patients, additional factors promoting the development of HCC included: advanced age, male sex, chronic hepatitis B (CHB) co-infection, and iron overload. For early diagnosis of HCC, sequential ultrasound screening is recommended especially for thalassemia patients with chronic hepatitis C (CHC), which coincides with (one or more) additional risk factors for HCC. Here we report also the preliminary data from thalassemic patients, above the age of 30 years, followed in 13 ICET-A centers. The total number of enrolled patients was 1,327 (males: 624 and 703 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.66 % and 1.96 %, respectively. The lowest age at diagnosis of HCC was 36 years for TDT and 47 years for NTDT patients. We hope that this review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia and to define specific international guidelines to support clinicians for early diagnosis and treatment of HCC in thalassemic patients.
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BACKGROUND: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. AIMS OF THE STUDY: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. RESULTS: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with ß- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions". CONCLUSIONS: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.
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Transfusión Sanguínea , Estado Civil , Paternidad , Talasemia/terapia , Adulto , Comorbilidad , Ferritinas/sangre , Humanos , Masculino , Talasemia/sangreRESUMEN
Changes in thyroid function and thyroid function tests occur in patients with ß-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients' genotype, age, ethnic heterogeneity, treatment protocols of transfusions and chelation, and varying compliance to treatment. Hypothyroidism is the result of primary gland failure or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland. The main laboratory parameters of thyroid function are the assessments of serum thyroid-stimulating hor-mone (TSH) and serum free thyroxine (FT4). It is of primary importance to interpret these measurements within the context of the laboratory-specific normative range for each test. An elevated serum TSH level with a standard range of serum FT4 level is consistent with subclinical hypothyroidism. A low serum FT4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism. Doctors caring for TM patients most commonly encounter subjects with subclinical primary hypothyroidism in the second decade of life. Several aspects remain to be elucidated as the frequency of thyroid cancer and the possible existence of a relationship between thyroid dysfunction, on one hand, cardiovascular diseases, components of metabolic syndrome (insulin resistance) and hypercoagulable state, on the other hand. Further studies are needed to explain these emerging issues. Following a brief description of thyroid hormone regulation, production and actions, this article is conceptually divided into two parts; the first reports the spectrum of thyroid disease occurring in patients with TM, and the second part focuses on the emerging issues and the open problems in TM patients with thyroid disorders.
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In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of physicians' current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.
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Enfermedades del Sistema Endocrino/epidemiología , Talasemia beta/complicaciones , Adolescente , Adulto , Factores de Edad , Niño , Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Adulto Joven , Talasemia beta/diagnóstico , Talasemia beta/terapiaRESUMEN
BACKGROUND: Loss-of-function mutations of fibroblast growth factor receptor 1 gene (FGFR1) have been reported so far. These mutations have been described in the extracellular domain, consisting of three Ig-like domains in the single transmembrane helix and in the intracellular region, containing a tyrosine kinase domain and cause about 10% of all cases of Kallmann syndrome. FRGR1 mutations could be associated with non reproductive phenotype such as cleft palate and dental agenesis and a wide spectrum of reproductive phenotype. CASE REPORT: The patient, 17 years and 11 months old, was a Bulgarian male referred to our Pediatric Endocrinology Unit for pubertal failure and hyposmia. Clinical evaluation revealed a highpitched voice, gynecomastia and obesity. Hormonal study revealed hypogonadotropic hypogonadism. Molecular analysis, performed by Next Generation Sequencing and confirmed by Sanger sequencing, led to the identification of a novel and previously undescribed mutation c.1058 C>G (p. S353C) in heterozygous state on exon 8 of the FGFR1 gene. CONCLUSION: The novel mutation, that we found in a boy with Kallman syndrome, could destabilize the D3 immunoglobulin like receptor domain that is crucial for the FGF-FGFR interaction. (www.actabiomedica.it).
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Síndrome de Kallmann/genética , Mutación Missense , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Adolescente , Humanos , MasculinoRESUMEN
Yolk sac tumor (YST) is a rare tumor that usually occurs in the first two decades of life. It is considered the second most common malignant germ cell tumor of the ovary, characterized by a rapid growth and a bad prognosis due to the frequent metastasis. We report the case of a 12-year-old girl who came to our observation for an acute abdominal pain. Clinical examination evidenced a vague mass in the suprapubic region and a lower abdomen tenderness, the US imaging revealed a complex lesion of the left ovary (19 x 13 cm) and the alpha-fetoprotein (AFP) resulted high (5858 ng/mL). Computed tomography (CT) revealed a large pelvic mass. The treatment consisted of debulking surgery of yolk sac tumor followed by 4 cycles of BEP protocol (Bleomycin, Etoposide, Cisplatin). After 3 years of follow-up there was no evidence of disease recurrence. (www.actabiomedica.it).
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Abdomen Agudo/etiología , Tumor del Seno Endodérmico/complicaciones , Neoplasias Ováricas/complicaciones , Adolescente , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/terapia , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapiaRESUMEN
We present a case of an 11-month-old girl who was referred to our unit for an erythematous rash that appeared on the face and extremities. Personal and family history was not relevant. Laboratory tests were normal. During recovery, diameter and colour intensity of the cutaneous lesions increased, but after some weeks, lesions had a self-limited resolution without any treatment. Based on clinical and laboratory findings, a diagnosis of acute hemorrhagic edema of infancy (AHEI) was made. AHEI is a rare cutaneous leukocytoclastic vasculitis that usually affects children aged between 4 and 24 months. Etiology is unknown but almost of 75% of cases are preceded by infectious episodes, vaccinations or use of medications. In contrast to the dramatic cutaneous eruption, clinical conditions are usually optimal. Classically, AHEI is characterized by a triad of symptoms: fever, edema and purpura. Skin lesions are erythematous, annular, medallion-like, purpuric plaques that have a rapid onset and appear on the face and extremities, sparing trunk and mucosal membranes. Initially interpreted as a variant of Henoch-Schönlein purpura, now it is considered a distinct disease. In the majority of cases the disease is benign and self-limited without a visceral involvement, so a conservative approach is most often chosen.
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Púrpura , Vasculitis Leucocitoclástica Cutánea , Enfermedad Aguda , Edema/complicaciones , Femenino , Hemorragia/complicaciones , Humanos , Lactante , Púrpura/complicaciones , Vasculitis Leucocitoclástica Cutánea/complicaciones , Vasculitis Leucocitoclástica Cutánea/diagnósticoRESUMEN
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper-immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α-directed migration. Gene transfer of ARPC1B in patients' T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8+ T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
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Complejo 2-3 Proteico Relacionado con la Actina/genética , Mutación de Línea Germinal , Síndromes de Inmunodeficiencia/genética , Linfocitos T/patología , Complejo 2-3 Proteico Relacionado con la Actina/química , Femenino , Homocigoto , Humanos , Síndromes de Inmunodeficiencia/patología , Masculino , Modelos Moleculares , Linaje , Conformación Proteica , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/patología , Linfocitos T/metabolismoRESUMEN
Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts.In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities.Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.