RESUMO
BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.
Assuntos
Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Testes Genéticos/métodos , Transportadores de Cassetes de Ligação de ATP/genética , Hiperinsulinismo Congênito/cirurgia , Diagnóstico Diferencial , Genótipo , Humanos , Recém-Nascido , Mutação , Fenótipo , Canais de Potássio/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Cuidados Pré-Operatórios , Receptores de Droga/genética , Receptores de SulfonilureiasRESUMO
We present three cases of primary hyperparathyroidism (PHPT) in pregnancy. The clinical presentation of PHPT is not altered by pregnancy; however, the disease constitutes a serious risk for the foetus and the newborn. Although rare, hypercalcaemia should be suspected in pregnant women presenting with polydipsia, polyuria and fatigue as well as hypertension or preterm labour.
Assuntos
Hiperparatireoidismo/diagnóstico , Complicações na Gravidez , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/cirurgia , Adulto , Feminino , Humanos , Hiperparatireoidismo/complicações , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/cirurgia , Gravidez , Complicações na Gravidez/diagnóstico , Resultado da GravidezAssuntos
Diabetes Mellitus Tipo 2 , Adolescente , Índice de Massa Corporal , Criança , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Obesidade/complicações , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Celiac disease (CD) is a complex inflammatory disorder of the small intestine, induced by dietary gluten in genetically susceptible individuals. CD is strongly associated with HLA-DQ2 and it has recently been established that gut-derived DQ2-restricted T cells from patients with CD predominantly recognize gluten-derived peptides in which specific glutamine residues are deamidated to glutamic acid by tissue transglutaminase. Recently, intestinally expressed human genes with high homology to DQ2-gliadin celiac T-cell epitopes have been identified. Single or double point mutations which would increase the celiac T-cell epitope homology, and mutation in these genes, leading to the expression of glutamic acid at particular positions, could hypothetically be involved in the initiation of CD in HLA-DQ2-positive children. Six gene regions with high celiac T-cell epitope homology were investigated for single-nucleotide polymorphisms using direct sequencing of DNA from 20 CD patients, 27 type 1 diabetes mellitus (T1DM) patients with associated CD, 24 patients with T1DM without CD and 110 healthy controls, all of Caucasian origin. No variants in any of these genes in any of the investigated groups were found. We conclude that gut-expressed human celiac epitope homologous peptides are unlikely to represent non-HLA risk factors in the development of celiac disease in Caucasians.
Assuntos
Doença Celíaca/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Variação Genética , Gliadina/genética , Antígenos HLA-DQ/genética , HumanosRESUMO
The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.