ABSTRACT
Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.
Subject(s)
Hypertriglyceridemia , Insulin Resistance , Lipodystrophy, Familial Partial , Lipodystrophy , Pancreatitis , Acute Disease , Female , Humans , Hypertriglyceridemia/complications , Lipodystrophy, Familial Partial/diagnosis , Lipodystrophy, Familial Partial/genetics , Lipodystrophy, Familial Partial/therapyABSTRACT
INTRODUCTION: Several pediatric studies have demonstrated that therapy using a conventional insulin pump improves glycemic control and quality of life. At the beginning of this study, a new tubeless insulin pump, Omnipod®, had recently been marketed in France. OBJECTIVES: Analyze the response of adolescents treated with multiple injections to the proposal to use this new medical device and compare both the quality of life and the glycemic control of adolescents according to their choice. MATERIAL AND METHODS: This was a prospective, observational study of adolescents aged 10-17 years who had type 1 diabetes for more than 1 year, all treated with multi-injection insulin delivery according to a basal-bolus regimen. They were separated into three groups: group A choosing to use the Omnipod® system, group B taking the time to think before making a decision, and group C choosing to keep their multi-injection therapy. The three groups were compared according to their quality of life with validated tools and glycemic control. RESULTS: Groups were formed with 30 (25%) patients in group A, 55 patients (45%) in group B, and 36 patients (30%) in group C. As to the WHO Well-Being Index, no significant difference appeared in the study for the patients in the three groups. An increased treatment satisfaction score was found, evolving from 3.79 ± 0.68 to 4.36 ± 0.56, p = 0.002 (group A) and from 3.87 ± 0.7 to 4.16 ± 0.7, p = 0.032 (group B), with no significant change for group C (from 4.39 ± 0.6 to 4.31 ± 0.62, p = 0.582). The wish to change treatment score improved for group A (from 4.14 ± 0.88 to 1.68 ± 0.9; p < 0.001) and group B (from 3.51 ± 1.05 to 1.84 ± 1; p < 0.001), with no significant change for group C (from 1.81 ± 0 0.98 to 1.61 ± 0.8; p = 0.432). There was no significant difference regarding HbA1c rates in the three groups. CONCLUSION: There was no significant difference in quality-of-life scores between adolescents who chose to switch from multiple injection to the tubeless patch pump and those who retained multi-injection treatment, but increased satisfaction was observed in the former group.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin Infusion Systems/psychology , Insulin/therapeutic use , Quality of Life/psychology , Adolescent , Blood Glucose/analysis , Diabetes Mellitus, Type 1/psychology , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Male , Patient Satisfaction , Prospective StudiesABSTRACT
AIM: Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. METHODS: Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. RESULTS: The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7 years, then IGF1 for 2 years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. CONCLUSION: Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10 years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.
Subject(s)
Antigens, CD/genetics , Child Development , Donohue Syndrome/drug therapy , Insulin Resistance/genetics , Insulin-Like Growth Factor I/therapeutic use , Mutation , Receptor, Insulin/genetics , Child , Child Development/drug effects , Child, Preschool , Donohue Syndrome/genetics , Donohue Syndrome/metabolism , Donohue Syndrome/physiopathology , Female , Follow-Up Studies , Hormone Replacement Therapy , Humans , Infant , Insulin-Like Growth Factor I/metabolism , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
The aim of the study was to evaluate, after the first year of a national information campaign, the effect on the frequency and severity of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in children and adolescents in France. The following data were collected during a 2-year period in people younger than 15 years of age at diagnosis of T1D, in 146 pediatric centers: age, sex, duration of symptoms, patient's previous care, clinical and biological signs, and family history of T1D. DKA was defined as pH<7.30 or bicarbonate<15mmol/L, severe DKA as pH<7.10 or bicarbonate <5mmol/L. During the 2nd year, an information campaign targeting health professionals and families was launched with the objective of reducing the time to diagnosis. Data were compared between the year before the campaign (year 0) and the first year of the campaign (year 1). The number of new cases of T1D was 1299 for year 0 and 1247 for year 1. Between year 0 and year 1, the rate of DKA decreased from 43.9% to 40.5% (P=0.08), exclusively due to the decrease of severe DKA from 14.8 to 11.4% (P=0.01). In the 0- to 5-year-old and 5- to 10-year-old age groups, the relative decrease in the rate of DKA was 13% and 15%, and 23% and 41% for severe DKA, respectively. In patients referred to the hospital by a pediatrician or who came at the family's initiative, the decrease was 34% and 7%, and 39% and 32% for severe DKA, respectively. No change was observed in the 10- to 15-year-old group or in those children who were referred by a general practitioner. In multivariate analyses, a higher DKA rate was associated with the young age of the child (<5 years), being hospitalized at the parents' initiative rather than being referred by a doctor, and the absence of a family history of T1D. A higher rate of severe DKA was associated with these last two factors but not with the child's age. The frequency of DKA at diagnosis of type 1 diabetes remains high in children and adolescents, but the first year of an information campaign decreased it. The results have also helped better define the strategy and targets of the continuing prevention campaign, to more efficiently reduce the morbidity and mortality of T1D at diagnosis in children and adolescents in France.
Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/epidemiology , Diabetic Ketoacidosis/prevention & control , Adolescent , Child , Child, Preschool , Diabetes Mellitus, Type 1/diagnosis , Diabetic Ketoacidosis/etiology , Female , France , Humans , Infant , Male , Severity of Illness Index , Time FactorsABSTRACT
OBJECTIVES: This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA. PATIENTS AND METHODS: Over a 1-year period, 1299 youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L. RESULTS: At the time of diagnosis, 26% of the children were aged 0-5 years, 34% were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9% (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA. CONCLUSION: DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients' age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/epidemiology , Adolescent , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Diabetic Ketoacidosis/blood , Fatigue/etiology , Female , Follow-Up Studies , France/epidemiology , Hospitalization/statistics & numerical data , Humans , Hyperglycemia/etiology , Infant , Infant, Newborn , Male , Parents , Polydipsia/etiology , Polyuria/etiology , Prevalence , Surveys and QuestionnairesABSTRACT
AIMS: At puberty, type 1 diabetes (T1D) among young girls can lead to excess body weight, insulin resistance, deterioration of glycaemic control and dyslipidaemia. Although biological factors contribute largely to such metabolic dysfunction, little is known of the role of behavioural factors such as physical activity and diet. METHODS: This study investigated the association between metabolic dysfunction measured after a 12-h overnight fast and behavioural factors, including diet (4-day diary) and physical activity (validated questionnaire), in 19 postmenarchal adolescent girls with T1D compared with 19 healthy girls. RESULTS: T1D girls displayed higher levels of fat mass, insulin resistance (higher plasma glucose, serum leptin and waist-to-hip ratios) and dyslipidaemia (higher LDL-C and apolipoprotein B levels, lower HDL-C and apolipoprotein A-1 levels). Also, contrary to what is usually observed in T1D adults, serum adiponectin, an important vessel protector, was not raised in T1D adolescent girls compared with healthy controls. Quantity and quality of dietary macronutrient intakes as well as physical activity levels were comparable in both groups, although the T1D girls with the poorest metabolic profiles reported having the healthiest diets (fewer total calories, more protein and less carbohydrates). However, in T1D girls, less physical activity and more time spent watching television were associated with poorer metabolic profiles (higher waist-to-hip ratios, fat mass and leptin levels, and lower adiponectin, HDL-C and apolipoprotein A-1 levels). CONCLUSION: Collectively, these data suggest that physical inactivity is linked to metabolic dysfunction to a greater extent than unhealthy dietary habits in postmenarchal T1D adolescent girls.
Subject(s)
Diabetes Mellitus, Type 1/metabolism , Exercise , Feeding Behavior , Menarche , Overweight/epidemiology , Weight Gain , Adolescent , Adolescent Behavior , Blood Glucose/metabolism , Body Mass Index , Diabetes Mellitus, Type 1/blood , Diet Records , Energy Intake , Fasting/blood , Female , Glycated Hemoglobin/metabolism , Humans , Insulin Resistance , Leptin/blood , Overweight/blood , Overweight/prevention & control , Quality of Life , Risk Factors , Surveys and Questionnaires , Waist-Hip RatioABSTRACT
OBJECTIVE: Adult height deficit seen in Turner syndrome (TS) originates, in part, from growth retardation in utero and throughout the first 3 years of life. Earlier diagnosis enables earlier therapeutic intervention, such as with recombinant human GH (r-hGH), which may help to prevent growth retardation. In this open-label, multicentre phase III study, we investigated efficacy and safety in r-hGH treatment in young girls with TS. SUBJECTS AND METHODS: Girls (n=61) aged <4 years with TS receiving 0.035-0.05âmg/kg per day r-hGH for 4 years were compared with an historical control group (n=51) comprising untreated, age- and height-matched girls with TS. The main outcome measure was change in height SDS (H-SDS). Other measures included changes in height velocity SDS, IGF1 levels and glucose metabolism. RESULTS: After 4 years, a gain in mean H-SDS of 1.0 SDS (from -2.33±0.73 to -1.35±0.86 SDS) was observed with r-hGH treatment, in contrast to the decrease in mean H-SDS of 0.3 SDS in the control group (from -2.09±0.81 to -2.44±0.73 SDS; P<0.0001). r-hGH treatment was the main predictor of H-SDS gain and accounted for 52% of variability (multivariate analysis). r-hGH was well tolerated. As expected, IGF1 levels rose with treatment. A case of transient glucose intolerance resolved after dietary adaptation. CONCLUSION: Early treatment with r-hGH helps to prevent natural evolution towards short stature in most girls with TS. IGF1 levels and glucose metabolism should be monitored routinely during r-hGH therapy.
Subject(s)
Body Height/drug effects , Growth Hormone/therapeutic use , Turner Syndrome/drug therapy , Turner Syndrome/pathology , Age Determination by Skeleton , Blood Cell Count , Blood Glucose/metabolism , Carbohydrate Metabolism/drug effects , Child, Preschool , Female , Glycated Hemoglobin/analysis , Growth/drug effects , Growth Hormone/adverse effects , Humans , Infant , Insulin-Like Growth Factor I/analysis , Karyotyping , Liver Function Tests , Longitudinal Studies , Treatment OutcomeABSTRACT
Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.
Subject(s)
Mutation , Nuclear Proteins/genetics , Adolescent , Adult , Alopecia/genetics , Arrhythmias, Cardiac/genetics , Basal Ganglia Diseases , Base Sequence , Child , Chromosomes, Human, Pair 2/genetics , Cohort Studies , Diabetes Mellitus/genetics , Humans , Hypogonadism/genetics , Intellectual Disability/genetics , Male , Molecular Sequence Data , Open Reading Frames/genetics , Ubiquitin-Protein Ligase ComplexesABSTRACT
AIM: The aim of the study was to assess the evolution of bone mineral density (BMD) in children with celiac disease and to evaluate the effect of a gluten-free diet (GFD). METHODS: Altogether, 44 children (31 girls and 13 boys) were followed-up. BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine (Hologic QDR 4500). Results are expressed as absolute values for BMD, and as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). Patients were divided into two groups according to whether they followed a diet without (n=34) or with (n=10) gluten for at least 1 year. All patients were clinically free of symptoms at the end of the follow-up. RESULTS: At inclusion, 26 patients (59%) were delayed in bone age, 17 children (38%) had a BMD/CA< or =1 S.D. and six (13.6%) had a BMD/CA< or =2 S.D., whereas nine children (20%) had a BMD/BA< or =1 S.D. and three (6.8%) had a BMD/BA< or =2 S.D. During the follow-up, the BMD increase was greater in the GFD group, as determined by the BMD/CA/year (+0.05+/-0.3 vs -0.34+/-0.4 S.D.; P<0.01) and BMD/BA/year (-0.02+/-0.4 vs -0.4+/-0.6 S.D.; P<0.05). The gain in BMD/BA was smaller in the GFD group because of their need to catch up in bone maturation. CONCLUSION: Celiac children not following a GFD show delays in both bone maturation and mineralization. This prospective study confirms the importance of maintaining a GFD in children with celiac disease until the end of skeletal mineralization even in asymptomatic patients following a non-restricted diet.
Subject(s)
Bone Density , Celiac Disease/diet therapy , Diet, Gluten-Free , Absorptiometry, Photon , Adolescent , Age Determination by Skeleton , Bone Development , Bone Diseases, Metabolic/diet therapy , Bone Diseases, Metabolic/etiology , Celiac Disease/complications , Celiac Disease/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Longitudinal Studies , Lumbar Vertebrae , Male , Prospective StudiesSubject(s)
Bone Density , Crohn Disease/physiopathology , Adolescent , Age Determination by Skeleton , Child , HumansABSTRACT
Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.
Subject(s)
GTP-Binding Protein gamma Subunits , Lipodystrophy/congenital , Lipodystrophy/genetics , Adolescent , Adult , Age of Onset , Alleles , Cohort Studies , Female , Genotype , Heterotrimeric GTP-Binding Proteins/genetics , Humans , Hyperlipidemias/genetics , Infant , Infant, Newborn , Lipodystrophy/metabolism , Lipodystrophy/mortality , Male , Mutation/genetics , Pedigree , Phenotype , Protein Isoforms/geneticsABSTRACT
Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
Subject(s)
Chromosomes, Human, Pair 11/genetics , GTP-Binding Protein gamma Subunits , Lipodystrophy/congenital , Lipodystrophy/genetics , Proteins/genetics , Acanthosis Nigricans/complications , Chromosomes, Human, Pair 9/genetics , Cluster Analysis , DNA Mutational Analysis , Diabetes Complications , Female , Genes, Recessive , Genetic Linkage , Genetic Markers , Genetic Testing , Haplotypes , Hepatomegaly/complications , Heterotrimeric GTP-Binding Proteins/genetics , Humans , Hyperandrogenism/complications , Hypertriglyceridemia/complications , Insulin Resistance/genetics , Lebanon/epidemiology , Lipodystrophy/complications , Lipodystrophy/epidemiology , Male , Middle Aged , Molecular Sequence Data , Mutation , Norway/epidemiology , Organ Specificity , Pedigree , Protein Structure, Tertiary , Proteins/metabolism , Sequence Homology, Amino AcidABSTRACT
Lipoatropic diabetes (LD) is a rare recessive autosomal disorder, mainly characterized by lipoatrophy with alterations in lipid metabolism and extreme insulin resistance. To identify molecular defects responsible for this disease, we tested the implication of 14 candidate genes coding for proteins involved either in insulin action, i.e. insulin receptor, insulin receptor substrate 1, insulin-like growth factor I receptor, diabetes-associated ras-like protein (Rad), and glycogen synthase, or in lipid metabolism, i.e. lipoprotein lipase; apolipoproteins CII, AII, and CIII; hepatic lipase; hormone-sensitive lipase; the beta 3-adrenergic receptor; leptin; and fatty acid-binding protein 2. To this end, haplotype and linkage analyses using genotyping with microsatellites in 10 consanguineous families provided us with powerful genetic tools. Our results show that in most families, lod scores at a null recombination fraction were less than -2. Haplotype analysis also argues against the involvement of these genes in LD. This implies that mutations in these genes are unlikely to make a major genetic contribution to LD.
Subject(s)
Consanguinity , Diabetes Mellitus, Lipoatrophic/genetics , Genetic Linkage , Adolescent , Adult , Child , Child, Preschool , Chromosome Mapping , Female , Haplotypes , Humans , Infant , Lod Score , Male , Microsatellite Repeats , Pedigree , Recombination, GeneticABSTRACT
OBJECTIVE: The higher frequency of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X-isochromosome, since previous reports of this aspect have included only small numbers of patients. DESIGN: Retrospective study of patients with Turner's syndrome investigated within the past 12 years. PATIENTS: Sixty-seven cases of Turner's syndrome were reviewed. MEASUREMENTS: Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti-thyroglobulin and anti-microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient. RESULTS: A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examination, was established in 20.9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X-isochromosome (57.3%, 9/16), compared to patients with other karyotypes (9.8%, 5/51) (P = 0.0001). CONCLUSIONS: Our results, obtained by investigation of a larger number of patients with an X-isochromosome karyotype than in previous reports, confirm conclusively that patients with X-isochromosome Turner's syndrome have an increased risk of developing thyroiditis.
Subject(s)
Isochromosomes , Thyroiditis, Autoimmune/genetics , Turner Syndrome/genetics , X Chromosome , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Karyotyping , Male , Retrospective Studies , Risk Factors , Thyroiditis, Autoimmune/complications , Turner Syndrome/complicationsABSTRACT
The authors report the case of a 14 year-old-girl presenting with a prolactin-secreting pituitary macroadenoma and followed over one year of bromocriptine therapy. They focus on the specific clinical features, on the medical management as initial therapy at this age, and on the interest of magnetic resonance imaging and spontaneous hormonal secretion studies for the diagnosis and follow-up.
Subject(s)
Bromocriptine/therapeutic use , Pituitary Neoplasms/drug therapy , Prolactinoma/drug therapy , Adolescent , Bromocriptine/pharmacology , Female , Follicle Stimulating Hormone/metabolism , Follow-Up Studies , Growth Hormone/metabolism , Humans , Luteinizing Hormone/metabolism , Magnetic Resonance Imaging , Pituitary Neoplasms/pathology , Prolactin/metabolism , Prolactinoma/pathologyABSTRACT
Clinical, radiological and biological features of 19 cases of serologically proven Mycoplasma pneumoniae pneumonia were compared with those of 21 cases of other types of pneumonia. Some clinical features were more frequent in M pneumoniae: patients older than 5 years, association with upper respiratory tract infection, skin rashes, acute course, unsuccessful treatment with penicillin. There were no specific radiological features. When compared with the complement fixation method, the serological diagnosis using agglutination technique appears to be more sensitive.
Subject(s)
Pneumonia, Mycoplasma/diagnosis , Acute Disease , Agglutination Tests , Child , Child, Preschool , Female , Humans , Lung/diagnostic imaging , Male , Pneumonia, Mycoplasma/blood , Pneumonia, Mycoplasma/diagnostic imaging , Pneumonia, Mycoplasma/epidemiology , Radiography , Retrospective StudiesABSTRACT
Four cases of psychosocial dwarfism are reported. The growth follow-up of these four children does not fit to the classical description of rapid improvement once separated from their defective or careless family. This illustrates the difficulties for some children to adapt themselves to a foster family and the need to refer them to an institutional center in order to solve their different somatic, nutritional and psychological problems, together with those of their family. In such cases the important growth retardation and hormonal changes may hide severe psychopathological troubles such as hyperkinetic syndrome, anxiety and, possibly, depression.
Subject(s)
Dwarfism/psychology , Intellectual Disability/physiopathology , Child, Preschool , Dwarfism/physiopathology , Dwarfism/therapy , Humans , Infant , Intellectual Disability/psychology , Intellectual Disability/therapy , Male , Time FactorsABSTRACT
The treatment of insulin-dependent diabetes mellitus in a child generates new constraints in the family and requires adjustments of the daily routine. Refusal of these changes may lead to poor compliance with the treatment regimen. Poor or mistaken daily results and repeated episodes of ketoacidosis may occur as a result. Clandestine injection of insulin responsible for apparently inexplicable episodes of hypoglycemia is less common. Three new cases are reported herein. Clinical diagnosis is fairly easy and biological findings can provide confirmation. Acknowledgement of the injections by the patient is important in order to gain insight into his or her motives. Depression is known to be common among diabetics and the injections may be a symptom of depression. Another possibility is that the child expects to achieve an "irrational recovery" from the disease by taking control over the treatment. Furthermore, a child with access to a highly active drug like insulin can use this situation to acquire and maintain exceptional status within the family. The diagnosis of factitious hypoglycemia requires in every case an in-depth evaluation which may lead to psychotherapy for the child or for the entire family.