Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.54754-6

Six New Cases Confirm The Clinical Molecular Profile Of Complete Combined 17α-hydroxylase/ 17,20-lyase Deficiency In Brazil.

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17α-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17α-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (> 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium ( 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17α-hydroxylase/17,20-lyase deficiency in Brazilian patients.54711-

Seis novos casos confirmam o perfil clínico molecular de deficiência combinada de 17 alfa-hidroxilase/17,20-liase no Brasil

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17&#945;-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17&#945;-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (&gt; 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium (< 2.8 mEq/L) and elevated progesterone levels (&gt; 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17&#945;-hydroxylase/17,20-lyase deficiency in Brazilian patients.Em 2004, segundo Costa-Santos e cols., p.W406R e p.R362C correspondiam a 50% e 32% dos alelos mutantes do gene CYP17A1, respectivamente, em 24 pacientes de 19 famílias brasileiras com deficiência da 17&#945;-hidroxilase. Apresentamos os dados cl&#957;nicos e moleculares de seis pacientes de três famílias consanguíneas brasileiras com deficiência da 17&#945;-hidroxilase. Todas as pacientes apresentavam hipogonadismo, amenorreia e hipertensão ao diagnóstico. Duas irmãs tinham cariótipo 46,XY, ambas com gônadas palpáveis na região inguinal. Todas tinham hipogonadismo hipergonadotrófico, com nível aumentado de ACTH (&gt; 104 ng/mL), atividade de renina plasmática suprimida, baixos níveis de potássio (< 2,8 mEq/L) e progesterona aumentada (&gt; 4,4 ng/mL). Três delas, incluindo duas irmãs, apresentaram homozigose para a mutação p.W406R e as outras três (duas irmãs e uma prima) foram homozigotas para a mutação p.R362C. A recorrência das mutações p.W406R e p.R362C no gene CYP17A1 aqui relatada em famílias adicionais confirma que essas são as mais frequentes causadoras do fenótipo completo da deficiência combinada de 17&#945;-hidroxilase/17,20-liase em pacientes brasileiros.71171