RESUMO
AIM: To compare the growth response to growth hormone (GH) treatment in patients with idiopathic GH deficiency (IGHD) who were prepubertal with the response of those who were pubertal at the onset of GH therapy on an increased GH dose. PATIENTS AND METHODS: Among the Turkish patients enrolled in the Pfizer International Growth Study (KIGS) database with the diagnosis of IGHD, the growth data over 2 years of GH therapy were analyzed longitudinally of 113 (79 M) prepubertal (Group 1) and 44 (33 M) pubertal (Group 2) patients. Pubertal signs were reported to be present initially or to have appeared within 6 months of GH therapy in Group 2. Mean +/- SD age at onset of therapy was 8.7 +/- 3.5 and 13.5 +/- 1.8 years; height SDS -4.2 +/- 1.4 and -3.2 +/- 1.1 (p < 0.05) in Groups 1 and 2, respectively. Mid-parental height (MPH) SDS did not show a significant difference between the two groups (-1.5 +/- 1.1 vs -1.7 +/- 1.1). RESULTS: Delta height SDS over 2 years of therapy was significantly higher in Group 1 (1.1 +/- 1.0) than in Group 2 (0.7 +/- 0.6) (p <0.05) in spite of a significantly lower dose of GH (14.6 +/- 3.3 in Group 1 vs 17.0 +/- 3.1 IU/m2/week in Group 2, p < 0.05). Ht--MPH SDS showed an increase from -2.4 +/- 1.7 to -1.4 +/- 1.5 in Group 1 and from -1.5 +/- 1.5 to -0.8 +/- 1.3 in Group 2. Overall delta height SDS showed negative correlations with age (r = -0.32), height SDS (r = -0.41) and height--MPH SDS (r = -0.40) at onset of therapy (p < 0.001). CONCLUSIONS: These data show that in IGHD the slight increase (15-20%) in the dose of GH during puberty was not adequate to maintain height velocity at the same magnitude as in prepuberty, and thus was not cost effective.
Assuntos
Estatura/efeitos dos fármacos , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/deficiência , Puberdade , Adolescente , Criança , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Nanismo Hipofisário/patologia , Nanismo Hipofisário/fisiopatologia , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento Humano/sangue , Humanos , Estudos Longitudinais , Masculino , TurquiaRESUMO
We identified a new nonsense mutation of the TSH-beta subunit gene responsible for a severe isolated TSH deficiency in two children from the same consanguineous kindred. These affected children are homozygous for a C-to-T transition at nucleotide 654 of the TSH-beta subunit gene, leading to the conversion of a glutamine (CAG) to a premature stop codon (TAG) in the codon 49 (Q49X). The resulting nascent peptide does not contain the seat belt region (amino acid residues 88-105), a TSH-beta subunit region crucial for the dimerization with the alpha-subunit, and, hence, the correct secretion of the mature TSH heterodimer is hampered. Free T(3), free T(4) as well as basal TSH levels were extremely low in both affected individuals and, importantly, TRH stimulations failed to increase serum TSH, but not PRL, confirming isolated TSH deficiency. Using the new StyI endonuclease restriction site generated by the mutation, we confirmed that the affected children were homozygous for the Q49X TSH-beta mutation whereas their unaffected parents as well as their unaffected brother were heterozygous. Consequently, this isolated TSH deficiency follows an autosomal recessive mode of inheritance.
Assuntos
Genes Recessivos/genética , Hipotireoidismo/genética , Mutação/genética , Tireotropina/genética , Substituição de Aminoácidos/genética , Hipotireoidismo Congênito , DNA/genética , DNA/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Feminino , Genoma , Humanos , Lactente , Masculino , Linhagem , Mapeamento por Restrição , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). Although pit-1 was 1 of the first factors identified as a cause of CPHD in mice, many other homeodomain and transcription factors have been characterized as being involved in different developmental stages of pituitary gland development, such as prophet of pit-1 (prop-1), P-Lim, ETS-1, and Brn 4. The aims of the present study were first to screen families and patients suffering from different forms of CPHD for PROP1 gene alterations, and second to define possible hot spots and the frequency of the different gene alterations found. Of 73 subjects (36 families) analyzed, we found 35 patients, belonging to 18 unrelated families, with CPHD caused by a PROP1 gene defect. The PROP1 gene alterations included 3 missense mutations, 2 frameshift mutations, and 1 splice site mutation. The 2 reported frameshift mutations could be caused by any 2-bp GA or AG deletion at either the 148-GGA-GGG-153 or 295-CGA-GAG-AGT-303 position. As any combination of a GA or AG deletion yields the same sequencing data, the frameshift mutations were called 149delGA and 296delGA, respectively. All but 1 mutation were located in the PROP1 gene encoding the homeodomain. Importantly, 3 tandem repeats of the dinucleotides GA at location 296-302 in the PROP1 gene represent a hot spot for CPHD. In conclusion, the PROP1 gene seems to be a major candidate gene for CPHD; however, further studies are needed to evaluate other genetic defects involved in pituitary development.
Assuntos
Proteínas de Homeodomínio/genética , Hormônios Hipofisários/deficiência , Hormônios Hipofisários/genética , Fatores de Transcrição/genética , Hormônio Adrenocorticotrópico/deficiência , Adulto , Processamento Alternativo , Animais , Feminino , Hormônio Foliculoestimulante/deficiência , Mutação da Fase de Leitura , Deleção de Genes , Genoma , Gonadotropinas/deficiência , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Humanos , Hormônio Luteinizante/deficiência , Masculino , Camundongos , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Polimorfismo Genético , Prolactina/deficiência , Tireotropina/deficiênciaRESUMO
The albumin excretion rate (AER), insulin-like growth factor-I (IGF-I) levels, glomerular filtration rate (GFR) and glycosylated hemoglobin (HbA1c) levels were studied in 49 diabetic children and 49 controls. The duration of diabetes varied from newly diagnosed to 17.5 years. Diabetics exhibited a wide range of AER values and had significantly higher AER and IGF-I levels compared to controls. At puberty elevated circulating growth hormone (GH) concentrations were found with a parallel increase in the levels of IGF-I. High IGF-I levels were found in 10-12 year-old girls and 15-16 year-old boys in both diabetic and control groups. Positive correlations were found between IGF-I and GFR in girls of both groups (p < 0.05) and in control girls between IGF-I, GFR and microalbuminuria (p < 0.05). The diabetic boys also showed microalbuminuria with respect to controls at high HbA1c levels and when their testis volume exceeded 8 ml (p < 0.05). We concluded that the prominent change in GH release at puberty, reflected by IGF-I, is in pulse amplitude, and that this is increased in diabetes but it is not a very important factor when determining the abnormal levels of urinary albumin excretion.
Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 1/fisiopatologia , Taxa de Filtração Glomerular , Fator de Crescimento Insulin-Like I/metabolismo , Puberdade , Adolescente , Adulto , Criança , Feminino , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento Humano/metabolismo , Humanos , Cinética , Masculino , Valores de ReferênciaRESUMO
A better understanding of the remission phase, while residual beta-cell function is still present in recently diagnosed type 1 (insulin dependent) diabetes mellitus (IDDM), is very important because of the potential for pharmacological intervention to preserve this function. To evaluate the natural course and characteristics of the remission phase in children and adolescents with IDDM, a retrospective study was performed on patients diagnosed with IDDM under the age of 18 years during the years 1991-1998. Sixty-two patients whose medical records were available were included in the study. Data were collected by reviewing the hospital records of patients from the time of diagnosis through the first 24 months after diagnosis. The duration of symptoms and history of infection prior to presentation, diabetic ketoacidosis (DKA) at diagnosis, length of hospitalization, initial glucose level, basal C-peptide levels at diagnosis, daily insulin requirements per kg body weight and HbA1c at diagnosis and at each visit were recorded. Thirty-five patients (56.5%) entered partial remission. We observed similar remission rates in those aged <10 and > or =10 years at diagnosis and in boys and girls. History of infection and presentation with DKA were associated with a lower rate of remission (p<0.001, p<0.0001, respectively) and were more commonly observed under the age of 10 years (p<0.0001, p<0.0001, respectively). The average insulin requirements per kg body weight calculated at diagnosis decreased with increasing age (r = -0.31, p = 0.012). The length of time until remission was 1.36+/-1.03 (mean +/- SD) months and positively correlated with insulin requirements at discharge from the hospital (r = 0.63, p<0.0001). Mean duration of remission was 11.67+/-5.82 months and was much longer in boys than girls (p<0.05). Six patients, all boys, entered total remission for 3.80+/-3.73 months. HbA1c concentrations in the first year of the disease were significantly lower in patients who underwent a remission phase (7.31+/-1.24% vs. 8.24+/-1.47%, p <0.05). However, this difference was not observed during the second year of the disease. In conclusion, history of infection prior to presentation and DKA at diagnosis were associated with young age and were the most important factors negatively influencing the remission rate in newly diagnosed IDDM patients.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/uso terapêutico , Indução de Remissão , Adolescente , Envelhecimento , Glicemia/análise , Peptídeo C/sangue , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/fisiopatologia , Cetoacidose Diabética/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Infecções/complicações , Insulina/administração & dosagem , Ilhotas Pancreáticas/fisiopatologia , Tempo de Internação , Masculino , Puberdade , Estudos RetrospectivosRESUMO
A 12 2/12 year-old boy was admitted to our hospital with the complaint of rapid growth. His birth and postnatal growth history, developmental retardation, physical examination and skeletal radiograms suggested Sotos syndrome. CT and MRI findings revealed septo-optic dysplasia (SOD), which is usually characterized by poor growth, together with cerebral gigantism in our case. These two entities are both rare and as far as we know this is the first patient in the literature with Sotos syndrome and SOD.
Assuntos
Transtornos do Crescimento/etiologia , Nervo Óptico/patologia , Septo Pelúcido/anormalidades , Determinação da Idade pelo Esqueleto , Agenesia do Corpo Caloso , Estatura , Criança , Humanos , Deficiência Intelectual , Imageamento por Ressonância Magnética , Masculino , Síndrome , Tomografia Computadorizada por Raios XRESUMO
The objective of this study was to evaluate the anthropometric parameters of short statured children examined in our outpatient clinic. 367 children were evaluated. Body weight for age, weight for height, height for age and body mass index of subjects were expressed as percent of standards. Wasting and stunting were established according to Waterlow's criteria /4/. Of 367 children, 27.8% were wasted and stunted; 59.1% were stunted; 3.8% had constitutional delay of growth and 9.3% had growth hormone deficiency. Ninety-seven percent of growth hormone deficient children had deficiency in weight as well as height. This study indicates that most short statured children and some growth hormone deficient children present with anthropometric indices of chronic nutritional deficiency in a country where nutritional deprivation is frequent.
Assuntos
Antropometria , Estatura , Avaliação Nutricional , Fatores Socioeconômicos , Adolescente , Fatores Etários , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Transtornos do Crescimento/etiologia , Humanos , Lactente , Distúrbios Nutricionais/complicaçõesRESUMO
The objective of this study was to investigate the vitamin A (vit A) status and beta carotene levels of children with constitutional delay of growth and puberty (CDGP). Serum vit A and beta-carotene levels of 26 children with CDGP were measured. 20 age-matched healthy children with normal pubertal development served as controls. Except for the height SDS, which was significantly lower in the CDGP group (p < 0.05), no significant differences were found between chronological ages, weight for height indices and beta-carotene levels of the two groups (p > 0.05). Although serum vit A levels of children in both groups were within normal limits according to WHO criteria, serum vit A levels were significantly lower in the CDGP group than in controls (44.13 +/- 12.25 and 59.60 +/- 19.75 micrograms/dl respectively, p < 0.05). It was concluded that vit A deficiency may play a role in CDGP in developing countries.
Assuntos
Transtornos do Crescimento/sangue , Puberdade Tardia/sangue , Vitamina A/sangue , Adolescente , Estatura , Peso Corporal , Feminino , Humanos , Masculino , Deficiência de Vitamina A/complicações , beta Caroteno/sangueRESUMO
Helicobacter pylori is a gastroduodenal pathogen strongly associated with chronic gastritis and duodenal ulceration. It is thought that H. pylori infection might be one of the causes of growth retardation in children. The aim of this study was to evaluate the seroprevalence of H. pylori in children with constitutional delay of growth and puberty (CDGP). H. pylori seropositivity was studied in 24 children with CDGP (22 M, 2 F) and 32 healthy age-matched children with normal pubertal development. Mean age of the children with CDGP was 14.53 +/- 1.12 yr and all of them had been diagnosed as CDGP after physical and laboratory assessment. H. pylori IgG positivity was detected in 16 of the 24 children with CDGP (66.6%) and 12 of 32 controls (37.5%) (p <0.05). This finding is consistent with the hypothesis that H. pylori infection could be one of the environmental factors causing CDGP.
Assuntos
Transtornos do Crescimento/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Puberdade Tardia/etiologia , Adolescente , Anticorpos Antibacterianos/análise , Estatura , Criança , Feminino , Transtornos do Crescimento/microbiologia , Transtornos do Crescimento/patologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/análise , Masculino , Valores de ReferênciaRESUMO
Breast enlargement with bloody discharge is very rare in childhood. We report a two year-old boy with breast enlargement and bloody discharge. Because of persistent bloody discharge, subcutaneous mastectomy was performed. The specimen showed histologic changes identical to those seen in adult mammary duct ectasia. We suggested that the infant's own endocrine system is responsible for breast enlargement and mammary duct ectasia, possibly occurring as a result of a mechanism similar to that in adults.
Assuntos
Doenças Mamárias/patologia , Mamilos/patologia , Sangue , Mama/patologia , Pré-Escolar , Exsudatos e Transudatos , Humanos , MasculinoRESUMO
Local lipoatrophy is a well known complication of insulin treatment at injection sites and the etiology is thought to be a cross reaction with lipid tissues and insulin antibody. Although mild lipoatrophy during growth hormone treatment has been reported in the literature, severe local lipoatrophy in injection sites in the extremities has not yet been published. We report a patient with isolated GH deficiency due to 6.7 kb gene deletion who received high dose rhGH treatment and developed local lipoatrophies at injection sites without any antibody detection after 6 years of therapy. The etiology of the lipoatrophy is suspected to be by the direct lipolytic effect of high doses of rhGH.
Assuntos
Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento/deficiência , Lipodistrofia/induzido quimicamente , Biópsia , Pré-Escolar , Feminino , Deleção de Genes , Hormônio do Crescimento/genética , Homozigoto , Humanos , Lipodistrofia/patologia , Pele/patologia , Fatores de TempoRESUMO
A 7-5/12 year-old girl, who was followed-up after diagnosis of indicanuria, presented with symptoms of bilateral breast enlargement. Her breast development was at Tanner stage II. No pubic or axillary hair was observed. Pelvic ultrasonography revealed multiple follicles on both ovaries. Basic endocrinological evaluation and cranial magnetic resonance imaging (MRI) were normal. The diagnosis of precocious puberty was established with respect to the pubertal response to GnRH stimulation test. Although precocious puberty has been reported associated with some metabolic diseases, this is the first description in a patient with indicanuria. The question of whether precocious puberty in our patient with indicanuria is a coincidence or whether it is related to metabolic changes activating the hypothalamo-pituitary-gonadal axis remains open.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/urina , Indicã/urina , Puberdade Precoce/complicações , Triptofano/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Criança , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Hormônio Luteinizante/sangue , Puberdade Precoce/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêuticoRESUMO
We report a 14 year-old peripubertal girl who presented at our clinic with the primary complaint of delayed puberty. She was asymptomatic except for vague complaints of fatigue. Physical examination was significant for mucosal hyperpigmentation and lack of secondary sexual characteristics. Laboratory evaluation revealed a morning cortisol concentration of <0.1 microg/dl (normal range [n.r.]: 4.3-22.4 microg/dl) and a simultaneous ACTH concentration of 2 pg/ml (n.r. 25-62 pg/ml); FSH 66.8 IU/l (n.r. for age: 1-12.8 IU/l); LH 41.1 IU/l (n.r. for age: 1-12 IU/l); E2 38 pg/ml (n.r. for age: 7-60 pg/ml). She had a flat cortisol response to an ACTH stimulation test. MRI of the pituitary gland failed to reveal a lesion. Plasma renin activity, thyroid function tests, parathyroid hormone, prolactin, IGF-I, IGFBP-3 concentrations and serum electrolytes were normal. However, her urinary sodium concentration was high. She was diagnosed with autoimmune polyglandular endocrinopathy including ovarian failure, adrenal failure and autoimmune anterior hypophysitis presenting as isolated ACTH deficiency. We emphasize that autoimmune etiology should be considered in the differential diagnosis of delayed puberty and ovarian failure and that the presence of other endocrinopathies should be searched for even in asymptomatic patients.
Assuntos
Doenças da Hipófise/complicações , Adeno-Hipófise , Poliendocrinopatias Autoimunes/complicações , Puberdade Tardia/complicações , Adolescente , Hormônio Adrenocorticotrópico/deficiência , Estradiol/uso terapêutico , Feminino , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Prednisolona/uso terapêutico , Puberdade Tardia/tratamento farmacológicoRESUMO
Type 1 diabetes mellitus (DM) is characterized by selective and progressive autoimmune destruction of beta-cells of the pancreas in genetically susceptible individuals. This autoimmune process takes years before the patient eventually develops clinical DM. Over the course of the disease, some patients regain their ability to secrete endogenous insulin to some extent for a period of few months to years. This partial remission phase has drawn a lot of attention since it offers a window of opportunity to intervene in an attempt to restore pancreatic beta-cell function or to prevent development of the disease in the prediabetic population at risk. Several factors, including age, sex, pubertal status, metabolic findings at the time of presentation, HLA types, presence of diabetes-associated autoantibodies, have been recognized to affect the likelihood of partial or complete remission in children with type 1 DM. Several interventions in patients with new-onset type 1 DM have been tried, including oral nicotinamide and immunomodulatory and immunosuppressive treatments, in an attempt to preserve beta-cell function and to promote or prolong the remission phase, but no conclusive data have been obtained so far. This review summarizes current knowledge on the factors that possibly influence the remission phase in children with type 1 DM.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Envelhecimento/fisiologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Humanos , Hipoglicemiantes/uso terapêutico , Imunoterapia , Insulina/uso terapêutico , Ilhotas Pancreáticas/fisiopatologia , Puberdade/fisiologia , Remissão Espontânea , Caracteres SexuaisRESUMO
Amelogenesis imperfecta (AI) is a diverse group of hereditary disorders that are characterized by a defect in the formation of the tooth enamel and a high degree of clinical diversity. X-linked, autosomal dominant and recessive inheritance have been demonstrated. Growth hormone (GH) has an effect on bone and soft tissue development. Dental and facial abnormalities associated with pituitary dwarfism have been reported, but GH deficiency with AI is very rare. We describe a 12 year-old pre-pubertal boy who was referred to our hospital with teeth deformities and growth retardation. His teeth had brown-yellow pigmented surfaces, and dental examination showed extensive enamel deficiency in his permanent teeth. He also had severe growth retardation; height SDS was -3.6. Laboratory examinations showed reduced GH levels, and he was diagnosed as having idiopathic isolated GH deficiency and AI.
Assuntos
Amelogênese Imperfeita/complicações , Amelogênese Imperfeita/diagnóstico , Hormônio do Crescimento Humano/deficiência , Amelogênese Imperfeita/genética , Criança , Transtornos do Crescimento/etiologia , Humanos , Masculino , LinhagemRESUMO
In a boy with non-Hodgkin's lymphoma (NHL), two different complications developed concurrently associated with L-asparaginase (L-ASP) therapy. A non-ketotic hyperglycemic state was observed simultaneously with bilateral acute parotitis after the patient was subjected to L-ASP. The hyperglycemia with normal insulin levels and the absence of plasma and urine ketones was controlled with insulin therapy and no residual impairment of glucose tolerance was demonstrated later. Bilateral acute parotitis, which is a rare complication associated with L-ASP, resolved spontaneously within a week after cessation of L-ASP. The rarely observed toxic effects of L-ASP, such as parotitis, should be recognized as promptly as the better-known complications, e.g., hyperglycemia, to avoid the continuation of this antineoplastic agent.
Assuntos
Asparaginase/efeitos adversos , Hiperglicemia/induzido quimicamente , Linfoma não Hodgkin/tratamento farmacológico , Parotidite/induzido quimicamente , Doença Aguda , Adolescente , Asparaginase/uso terapêutico , Escherichia coli/enzimologia , Humanos , Hiperglicemia/tratamento farmacológico , Insulina/uso terapêutico , MasculinoRESUMO
Growth retardation is a common feature of mucopolysaccharide storage disorders, mostly considered to be a consequence of skeletal changes, Maroteaux-Lamy disease is a subtype of mucopolysaccharidosis, demonstrating somatic changes and skeletal deformities. We present a case with Maroteaux-Lamy disease associated with growth hormone deficiency. Magnetic resonance imaging study revealed marked signal changes in white matter due to the storage in brain and empty sella appearance in sellar region. In the presence of empty sella syndrome, hypothalamic-pituitary dysfunction due to the storage material may have led to growth hormone deficiency in this patient. Therefore, we recommend patients with mucopolysaccharidosis, especially those who have growth retardation, to be evaluated by hormonal and radiological studies.
Assuntos
Hormônio do Crescimento/deficiência , Mucopolissacaridose VI/complicações , Pré-Escolar , Consanguinidade , Hormônio do Crescimento/sangue , Humanos , Lactente , Insulina , Levodopa , Imageamento por Ressonância Magnética , Masculino , Mucopolissacaridose VI/diagnósticoRESUMO
Diabetic cardiomyopathy (DC) has been reported in type 2 diabetics with short duration of clinically overt diabetes. Impaired left ventricular function has been reported in young patients with diabetes mellitus type 1 (IDDM), but severe cardiomyopathy as the first early major complication of IDDM is very rare. We report a 14 year-old girl with a 5-year history of IDDM and very poor compliance with treatment and follow-up. She was referred to our clinic upon the development of congestive heart failure and dilated cardiomyopathy was diagnosed based on clinical findings, electrocardiogram, chest X-ray and echocardiography. She had no evidence of other major complications of IDDM such as retinopathy, nephropathy or neuropathy.
Assuntos
Cardiomiopatia Dilatada/diagnóstico , Angiopatias Diabéticas/diagnóstico , Adolescente , Diabetes Mellitus Tipo 1 , Ecocardiografia , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Radiografia Torácica , Disfunção Ventricular Esquerda/diagnósticoRESUMO
Familial growth hormone deficiency type 1A is an autosomal recessive disease, caused by various homogenous deletions of both alleles of growth hormone gene 1 (hGH1). The hGH1 gene deletion is an event occurring between the 5' and the 3' flanking regions by unequal recombination, which causes a deletion in the hGH1 gene, mostly of 6.7 kb and rarely 7.6 or 7.0 kb in size. Two brothers diagnosed with GH deficiency syndrome were sent to our hospital for further evaluation. DNA samples of the probands and controls were amplified by PCR; restriction endonuclease analysis was done with Sma I enzyme and the patterns were evaluated. Gel electrophoresis results showed that the two brothers had a 7.0 kb deletion. These are the third and fourth cases reported with a 7.0 kb deletion. Both patients responded well to replacement therapy and did not develop antibodies against rGH. No other relatives presented with macro deletions in the hGH1 gene.
Assuntos
Deleção de Genes , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/genética , Criança , DNA/análise , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Eletroforese em Gel de Ágar , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
MHC class I antigen expression was found to be low on the lymphocytes of patients with insulin dependent diabetes mellitus (IDDM). Thus, it has been proposed that the defective expression of MHC antigens could lead to faulty immunological responses with the eventual destruction of the pancreatic beta cells. The objective in this study was to compare MHC antigen expression in IDDM patients and their presently healthy siblings. Nineteen children (mean age 10.8 +/- 3.9 years) with diabetes and their 25 siblings (mean age 10.7 +/- 4.6 years) were enrolled in the study. Peripheral blood lymphocytes isolated from venous blood samples were incubated with FITC conjugated monoclonal antibody W6/32. The amount of antibody binding by cell surface MHC class I antigens was assessed by flow cytometry. MHC class I molecule expression did not differ significantly among IDDM patients and their siblings. It was concluded that MHC class I antigen expression did not appear to be indicative of a susceptibility to develop autoimmune diabetes.