Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gs{alpha} coding mutations and GNAS imprinting defects.

BACKGROUND: Pseudohypoparathyroidism (PHP) defines a rare group of disorders whose common feature is resistance to the parathyroid hormone. Patients with PHP-Ia display additional hormone resistance, Albright hereditary osteodystrophy (AHO) and reduced Gsalpha activity in easily accessible cells. This form of PHP is associated with heterozygous inactivating mutations in Gsalpha-coding exons of GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib typically have isolated parathyroid hormone resistance, lack AHO features and demonstrate normal erythrocyte Gsalpha activity. Instead of coding Gsalpha mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at least in some cases, by genetic mutations within or nearby this gene. PATIENTS: Two unrelated PHP families, each of which includes at least one patient with a Gsalpha coding mutation and another with GNAS loss of imprinting, are reported here. RESULTS: One of the patients with GNAS imprinting defects has paternal uniparental isodisomy of chromosome 20q, explaining the observed imprinting abnormalities. The identified Gsalpha coding mutations include a tetranucleotide deletion in exon 7, which is frequently found in PHP-Ia, and a novel single nucleotide change at the acceptor splice junction of intron 11. CONCLUSIONS: These molecular data reveal an interesting mixture, in the same family, of both genetic and epigenetic mutations of the same gene.

Colelitiasis como causa infrecuente de dolor abdominal en el niño / Choleithiasis as a rare cause of abdominal pain in the child

El dolor abdominal es un síntoma frecuente en la infancia que puede aparecer hasta en un 10-15% de los niños siendo la patología de la vesícula biliar responsable de un pequeño porcentaje de los casos. Es difícil conocer la prevalencia exacta de la litiasis biliar en niños porque muchos pacientes están asintomáticos y la gran difusión de la ecografía ha sido la que ha permitido establecerla mejor. Al igual que en adultos los tres tipos principales de cálculos biliares son de colesterol, pigmento negro y pigmento marrón, cada uno asociado con diferentes enfermedades. La forma de presentación de la patología biliar depende de la enfermedad asociada, siendo lo más frecuente la aparición de síntomas biliares. La ecografía abdominal se considera la prueba de imagen de elección para el diagnóstico y seguimiento. Tras el diagnóstico la actitud terapéutica varia según la sintomatología y puede ir desde un seguimiento clínico periódico, hasta tratamiento médico con ácido ursodesoxicólico o cirugía, siendo la colecistectomía laparoscopia la técnica de elección (AU)

Abdominal pain has been reported to occur in 10-15% of children but the presence of gallstones is the cause of very few cases. Ascertaining the true prevalence of gallbladder stones in children is difficult because many patients are asymptomatic. The introduction of ultrasonography allowed noninvasive screening for gallstone disease and therefore a more accurate estimate of prevalence. As in adults there are three major types of stones: cholesterol, black pigment and brown pigment each type associated with different diseases. The presentation of gallbladder disease depends on the underlying disease and the most frequent clinical presentation is with biliary symptoms. The ultrasonography is firmly established as the gold standard diagnostic procedure. After the diagnosis patients can be followed clinically without other treatment because the benign course of gallstones in children, also medical treatment with ursodeoxycholic acid is indicated in oligsymptomatic patients. Laparoscopic cholecytectomy is the procedure of choice in children requiring cholecystectomy, mainly in patients with underlying diseases (AU)