ABSTRACT
BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.
Subject(s)
Addison Disease , Candidiasis, Chronic Mucocutaneous , Hypoparathyroidism , Interferon Type I/immunology , Polyendocrinopathies, Autoimmune , Transcription Factors/genetics , Addison Disease/diagnosis , Addison Disease/etiology , Adult , Autoantibodies/blood , Candidiasis, Chronic Mucocutaneous/diagnosis , Candidiasis, Chronic Mucocutaneous/etiology , Female , Humans , Hypoparathyroidism/diagnosis , Hypoparathyroidism/etiology , Italy/epidemiology , Male , Mortality , Mutation , Polyendocrinopathies, Autoimmune/diagnosis , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/mortality , Polyendocrinopathies, Autoimmune/physiopathology , Prevalence , AIRE ProteinABSTRACT
PURPOSE: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. METHODS: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. RESULTS: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from - 2.41 ± 0.73 at baseline (n = 238) to - 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from - 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). CONCLUSIONS: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.
Subject(s)
Biosimilar Pharmaceuticals/therapeutic use , Growth Disorders/drug therapy , Human Growth Hormone/therapeutic use , Product Surveillance, Postmarketing/methods , Child , Female , Follow-Up Studies , Growth Disorders/epidemiology , Humans , Longitudinal Studies , Male , PrognosisABSTRACT
Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.
Subject(s)
Brain/pathology , Brain/physiopathology , Kallmann Syndrome/pathology , Kallmann Syndrome/physiopathology , Adolescent , Adult , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Diffusion Tensor Imaging , Globus Pallidus/pathology , Globus Pallidus/physiopathology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/pathology , Motor Cortex/physiopathology , Psychomotor Performance/physiology , Pyramidal Tracts/pathology , Pyramidal Tracts/physiopathology , Young AdultABSTRACT
PURPOSE: Despite international guidelines being available, not all gender clinics are able to face gender dysphoric (GD) youth population needs specifically. This is particularly true in Italy. Centers offering specialized support are relatively few and a commonly accepted Italian approach to GD youth has still not been defined. The aim of the present Position Statement is to develop and adhere to Italian guidelines for treatment of GD adolescents, in line with the "Dutch Approach", the Endocrine Society (ES), and the World Professional Association for Transgender Health (WPATH) guidelines. METHODS: An in-depth brainstorming on the application of International guidelines in the Italian context was performed by several dedicated professionals. RESULTS: A staged approach, combining psychological support as well as medical intervention is suggested. In the first phase, individuals requesting medical help will undergo a psycho-diagnostic procedure to assess GD; for eligible adolescents, pubertal suppression should be made available (extended diagnostic phase). Finally, from the age of 16 years, cross-sex hormonal therapy can be added, and from the age of 18 years, surgical sex reassignment can eventually be performed. CONCLUSIONS: The current inadequacy of Italian services offering specialized support for GD youth may lead to negative consequences. Omitting or delaying treatment is not a neutral option. In fact, some GD adolescents may develop psychiatric problems, suicidality, and social marginalization. With access to specialized GD services, emotional problems, as well as self-harming behavior, may decrease and general functioning may significantly improve. In particular, puberty suppression seems to be beneficial for GD adolescents by relieving their acute suffering and distress and thus improving their quality of life.
Subject(s)
Counseling , Puberty , Sex Reassignment Procedures , Transsexualism/therapy , Adolescent , Humans , Italy , Transsexualism/drug therapy , Transsexualism/psychology , Transsexualism/surgeryABSTRACT
INTRODUCTION: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease included in an emerging class of genetic disorders called 'ciliopathies' and is likely to impact the central nervous system as well as metabolic and endocrine function. Individuals with ALMS present clinical features resembling a growth hormone deficiency (GHD) condition, but thus far no study has specifically investigated this aspect in a large population. MATERIAL AND METHODS: Twenty-three patients with ALMS (age, 1-52 years; 11 males, 12 females) were evaluated for anthropometric parameters (growth charts and standard deviation score (SDS) of height, weight, BMI), GH secretion by growth hormone-releasing hormone + arginine test (GHRH-arg), bone age, and hypothalamic-pituitary magnetic resonance imaging (MRI). A group of 17 healthy subjects served as controls in the GH secretion study. Longitudinal retrospective and prospective data were utilized. RESULTS: The length-for-age measurements from birth to 36 months showed normal growth with most values falling within -0·67 SDS to +1·28 SDS. A progressive decrease in stature-for-age was observed after 10 years of age, with a low final height in almost all ALMS subjects (>16-20 years; mean SDS, -2·22 ± 1·16). The subset of 12 patients with ALMS tested for GHRH-arg showed a significantly shorter stature than age-matched controls (154·7 ± 10·6 cm vs 162·9 ± 4·8 cm, P = 0·009) and a mild increase in BMI (Kg/m(2) ) (27·8 ± 4·8 vs 24·1 ± 2·5, P = 0·007). Peak GH after GHRH-arg was significantly lower in patients with ALMS in comparison with controls (11·9 ± 6·9 µg/l vs 86·1 ± 33·2 µg/l, P < 0·0001). Severe GHD was evident biochemically in 50% of patients with ALMS. The 10 adult ALMS patients with GHD showed a reduced height in comparison with those without GHD (149·7 ± 6·2 cm vs 161·9 ± 9·2 cm, P = 0·04). MRIs of the diencephalic and pituitary regions were normal in 11 of 12 patients. Bone age was advanced in 43% of cases. CONCLUSIONS: Our study shows that 50% of nonobese ALMS patients have an inadequate GH reserve to GHRH-arg and may be functionally GH deficient. The short stature reported in ALMS may be at least partially influenced by impairment of GH secretion.
Subject(s)
Alstrom Syndrome/metabolism , Body Height , Body Weight , Growth Disorders/metabolism , Growth Hormone/deficiency , Adolescent , Adult , Alstrom Syndrome/genetics , Alstrom Syndrome/physiopathology , Body Mass Index , Cell Cycle Proteins , Child , Child, Preschool , Diencephalon/diagnostic imaging , Diencephalon/pathology , Female , Growth Disorders/genetics , Growth Disorders/physiopathology , Growth Hormone/metabolism , Humans , Infant , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Pituitary Gland/diagnostic imaging , Pituitary Gland/pathology , Proteins/genetics , Radiography , Retrospective Studies , Young AdultABSTRACT
Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture.
ABSTRACT
Gallbladder polypoid lesions are rare in the pediatric patient and sometimes represent an incidental finding. A 13 year old male was referred to the Padua Hospital Pediatric Department for an obesity. A routine abdominal ultrasound (US) detected a gallbladder polypoid lesion 6 mm in diameter, initially considered a gallbladder adenoma. Investigation did not detect any other biliary tract abnormality. After seven months, the asymptomatic patient underwent a follow-up US which revealed the disappearance of the polypoid mass. The following concerns are raised: what is the size of the polypoid mass that should be considered for surgery? How does the presence of symptoms worsen the diagnosis and lead to preferring a surgical approach (cholecystectomy) over an echographic follow-up?
Subject(s)
Gallbladder Diseases/diagnosis , Polyps/diagnosis , Adolescent , Adult , Diagnosis, Differential , Follow-Up Studies , Gallbladder Diseases/diagnostic imaging , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/diagnostic imaging , Humans , Male , Polyps/diagnostic imaging , Radiography, Abdominal , Remission, Spontaneous , Time Factors , UltrasonographyABSTRACT
In this study, we describe a pentaplex PCR to determine the parental origin of the X chromosome and the presence of mosaicism, via amplification of four polymorphic markers located along the X chromosome (DXS10011, DXS6807, HUMARA, DXS101) and the X-Y amelogenin marker, in 41 families having a daughter with Turner Syndrome. Our results confirmed the cytogenetic findings and we found that the parental origin of the single X chromosome to be maternal in 84% of cases.
Subject(s)
Chromosomes, Human, X , Chromosomes, Human, Y , Polymerase Chain Reaction/methods , Turner Syndrome/genetics , Adult , Amelogenin , Child , Child, Preschool , Dental Enamel Proteins/genetics , Family , Female , Genetic Markers , Humans , Mosaicism , Polymorphism, Genetic , Sex Chromosome AberrationsABSTRACT
About 2-3% of "essential" obesity in pediatric age is of endocrine or genetic origin (secondary obesity). The clinical picture of these forms is almost always characteristic; however, some patients affected by secondary obesity can present with an incomplete or atypical aspect. The aim of this review is to offer the pediatrician useful indications to correctly diagnose children presenting with obesity. It is advisable to make a careful anamnesis and an accurate medical examination in order to ascertain the causes that may have contributed to the onset and increase of weight gain. Obesity associated with mental retardation, short stature, cryptorchidism or hypogonadism, dysmorphism with facies sui generis, ocular or uditive defects, might suggest a genetic origin. Prader-Willi syndrome is the most frequent of these disorders and it is due to an alteration of chromosome 15 of paternal origin. These patients have to undergo the methilation test (easy and low cost genetic research) in order to confirm the clinical suspicion. Endocrine alterations, that play a pathogenic role in pediatric obesity (i.e., hypothyroidism, hypothalamic-pituitary diseases, pseudohypoparathyroidism), are rare. Early treatment of hormonal dysfunction generally allows to ameliorate or normalize the weight gain. In absence of specific clinical manifestations or lacking a significant clinical history, no endocrine test is required. The family pediatrician should require some routine hematochimic tests, in order to evaluate the possible presence of hyperlipidemia and/or glycometabolic complications. An oral glucose tolerance test is necessary only for patients presenting with serious weight gain, acanthosis nigricans, and for those with a family history of diabetes. In the most serious cases, a careful cardiovascular and respiratory evaluation should be performed. Children with a suspicion of secondary obesity have to be submitted to an endocrinologist, for a correct diagnosis and a specific treatment. However, the family pediatrician's assistance is essential during the follow-up period, in order to assure the patient and his/her family a proper assistance.
Subject(s)
Obesity/diagnosis , Adolescent , Bardet-Biedl Syndrome/diagnosis , Body Height , Body Weight , Child , Child, Preschool , Chromosomes, Human, Pair 15/genetics , Diabetes Mellitus/diagnosis , Diabetes Mellitus/genetics , Diagnosis, Differential , Female , Glucose Tolerance Test , Humans , Infant, Newborn , Male , Obesity/complications , Obesity/etiology , Obesity/genetics , Obesity/therapy , Prader-Willi Syndrome/diagnosis , Prader-Willi Syndrome/geneticsABSTRACT
An 11-year prospective study was carried out in 226 patients with organ-specific autoimmune disease (OSAD) coming from northern Italy and southern England. Patients were investigated for diabetes-related autoantibodies (ICAs, GADAbs, and IA2Abs) in order to evaluate the best immunological combination in predicting type 1 DM. One hundred twenty-eight patients were ICA positive (77 Italian and 51 English), and 98 were ICA negative. ICAs were detected by immunofluorescence technique on human pancreas, whereas GADAbs and IA2Abs were found by immunoprecipitation assay. During follow-up, 33 of 128 (25.8%) ICA(+) (26% of Italian and 25.5% of English) and 2 of 98 (2%) ICA(-) patients developed type 1 DM (17 with acute-onset, and 18 with non-acute-onset disease). Among ICA(+) patients, three subgroups were considered: ICA(+) alone; ICA and GADAb(+); ICA, GADAb, and IA2Ab(+). Patients who were only ICA(+) had a predictive value for type 1 DM of 4.7%, with an annual incidence of 0.7%, and a cumulative risk of 6%. ICA and GADAb(+) patients had a predictive value of 17.5%, with an annual incidence of 2%, and a cumulative risk of 20%. ICA, GADAb, and IA2Ab(+) patients had a predictive value of 72, with an annual incidence of 13%, and a cumulative risk of 87%. Patients having three immunological markers revealed a prevalence increased in HLA-DR3 and/or -DR4, but reduced in HLA-DR2 haplotypes. The risk for type 1 DM increased proportionally with the number of diabetes-related antibodies, which were also related to the presence of genetic markers of disease susceptibility.
Subject(s)
Autoimmunity/immunology , Diabetes Mellitus, Type 1/immunology , Pancreas/immunology , Adult , Biomarkers/analysis , Child , Disease Susceptibility , England , Female , Follow-Up Studies , Humans , Italy , Male , Organ Specificity , Risk FactorsABSTRACT
AIMS: Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition. METHODS: A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL). RESULTS: Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes. CONCLUSIONS: These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.
Subject(s)
Antiviral Agents/therapeutic use , Autoantibodies/analysis , Autoimmune Diseases/genetics , Hepatitis C, Chronic/therapy , Histocompatibility Antigens Class II/genetics , Interferon-alpha/therapeutic use , Adolescent , Adult , Autoimmune Diseases/immunology , Autoimmunity , Child , Child, Preschool , DNA/analysis , Electrophoresis, Polyacrylamide Gel , Female , Follow-Up Studies , Hepatitis C/immunology , Hepatitis C Antibodies/analysis , Hepatitis C, Chronic/immunology , Histocompatibility Antigens Class II/immunology , Humans , Interferon alpha-2 , Islets of Langerhans/immunology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prospective Studies , Recombinant Proteins , Thyroglobulin/immunology , Thyroid Gland/immunologySubject(s)
Polyendocrinopathies, Autoimmune/physiopathology , Addison Disease/immunology , Autoantibodies/blood , Autoimmune Diseases/physiopathology , Endocrine System Diseases/physiopathology , HLA Antigens/genetics , Humans , Hyperparathyroidism/physiopathology , Polyendocrinopathies, Autoimmune/epidemiology , Polyendocrinopathies, Autoimmune/immunology , PrevalenceABSTRACT
A 29-year-old man was observed to develop insulin-dependent diabetes mellitus following a 5-month treatment with recombinant alpha-2b-interferon for chronic hepatitis C. After the onset of the disease, serum samples that had, respectively, been collected before therapy commencement, at month 3, and at the onset of insulin-dependent diabetes mellitus were tested for islet-cell (ICA-IgG), glutamic acid decarboxylase (GAD-Abs), IA2 (IA2-Abs) and insulin (IA-Abs) autoantibodies. The following results were obtained: ICA-IgG, 5, >80, and >80 JDF-U, respectively; GAD-Abs: >100 U/ml in all three measurements; IA2-Abs and IA-Abs: negative. During treatment, thyroid microsomal autoantibodies increased markedly (from 1:100 to 25,600 titer); thyroid-stimulating hormone was persistently normal. HLA class II typing revealed a genetic predisposition to insulin-dependent diabetes mellitus as demonstrated by the presence of DRB1* 04/08, DQ A1 52 Arg+/Arg+, and DQB1 57 N-Asp/Asp alleles. One year after the onset of insulin-dependent diabetes mellitus, the patient is still receiving 30 IU insulin daily; the liver function tests are normal and HCV-RNA is negative. These data support the hypothesis that, in predisposed patients, alpha-interferon therapy can enhance an ongoing autoimmune process against pancreatic beta-cells and induce overt insulin-dependent diabetes mellitus. We therefore suggest that, in patients with a documented predisposition to insulin-dependent diabetes mellitus, alpha-IFN therapy should be administered with caution.
Subject(s)
Diabetes Mellitus, Type 1/etiology , Hepatitis, Viral, Human/therapy , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Adult , Autoimmunity/immunology , Biomarkers/analysis , Chronic Disease , Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , Humans , Male , Pancreas/immunology , Retrospective StudiesABSTRACT
Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylases (21-OH), steroid 17 alpha-hydroxylase (17 alpha-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17 alpha-OH and/or P450scc. During the prospective study, overt Addison's disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison's disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17 alpha-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison's disease.
Subject(s)
Addison Disease/etiology , Adrenal Cortex/immunology , Autoantibodies/analysis , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Steroid 21-Hydroxylase/immunology , Adult , Biomarkers , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Organ Specificity , Prospective StudiesABSTRACT
Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA were found in 14 children (1.7%), mostly in hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative children were followed up for a maximum of 10 yr by evaluation of adrenocortical function (ACTH test) and autoantibody status. In all patients steroid-producing cell autoantibodies were assessed by immunofluorescence and autoantibodies to steroid 21-hydroxylase, 17 alpha-hydroxylase, and cytochrome P450 side-chain cleavage enzyme by immunoprecipitation assay. All 10 ACA-positive patients were positive for 21-hydroxylase autoantibodies. Six were positive for steroid-producing cell autoantibodies and 5 also for autoantibodies to 17 alpha-hydroxylase and/or P450 side-chain cleavage enzyme. Overt Addison's disease developed in 9 (90%) ACA/21-OH-antibody-positive children after 3-121 months, and 1 remaining child had subclinical hypoadrenalism. By contrast, all ACA/21-OH antibody-negative children maintained normal adrenal function. Adrenal failure was not related to ACA titres, sex, adrenal function, type of preexisting autoimmune disorder, or human leucocyte antigens D-related status. In conclusion, in children with autoimmune endocrine diseases, ACA/21-hydroxylase autoantibodies are important predictive markers for the development of Addison's disease.
Subject(s)
Addison Disease/etiology , Adrenal Cortex/immunology , Autoantibodies/analysis , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Steroid 21-Hydroxylase/immunology , Biomarkers , Child , Child, Preschool , Disease Progression , Female , Follow-Up Studies , Humans , Male , Organ Specificity , Prospective StudiesABSTRACT
Sex determination in both fetuses and infants with ambiguous external genitalia usually necessitates time-consuming and costly karyotyping. We propose a simple, rapid, and reliable method of prenatal and postnatal sex determination by means of the PCR, a technique currently used to identify gender for forensic purposes. DNA was extracted from 20 samples of whole blood from infants with ambiguous genitalia and from five samples of amniotic fluid. Three markers were amplified from each specimen: a Y chromosome alphoid repeat sequence and two homologous genes, amelogenin (AME) and zinc finger protein (ZFP). All three were detected in under 10 hr. A comparison of the results obtained with those of cytogenetic analysis of the same samples showed a perfect sex match, demonstrating that this PCR technique provides an accurate means of determining gender.
Subject(s)
Genitalia/abnormalities , Polymerase Chain Reaction , Prenatal Diagnosis , Sex Determination Analysis , Amelogenin , Amniocentesis , Dental Enamel Proteins/genetics , Female , Humans , Male , Repetitive Sequences, Nucleic Acid , Y Chromosome/genetics , Zinc FingersABSTRACT
RFLP HLA-DRB1 analysis was performed on a total of 83 children born from HIV-infected mothers, 35 of whom were shown to be HIV-infected, while 48 reverted from seropositivity to seronegativity, indicating that they were not infected. Moreover, 89 healthy children were used as controls. It has been found that DRB1-14a and DRB1-13a.4 alleles were not present in the HIV-infected children, but were found in the sero-reverted (HIV-uninfected) children (in the proportion of 9.6 per cent and 5.3 per cent, respectively), and in the controls (5.6 per cent and 3.9 per cent, respectively). The possible correlation between DR and risk of HIV transmission from mother to baby was analysed considering every single allele, estimated by the ratio between the number of infected children and the number of all children born from seropositive mothers. There was also introduced a statistic G for the control of 'statistical validity' of data.