O Valor dos Indices Plaquetários na Púrpura Trombocitopénica Imune e Leucémia Linfo e Mieloblástica Aguda. Bases Clínico-Laboratoriais no Contributo para o Diagnóstico Diferencial Entre Estas Duas Patologias

Os autores apresentam um trabalho onde se pretende avaliar a utilidade dos índices plaquetários — volume plaquetário médio (VPM) e o coeficiente de variação do diâmetro plaquetário (CVDP ou PDW = Platelet Distribution Width) — e do número de plaquetas (PLAQ) no diagnóstico diferencial da trombocitopénia na púrpura trombocitopénica aguda (PTI) e na leucémia linfoblástica ou mieloblástica aguda (LLAULMA). Do mesmo modo, estudam comparativamente os dados clínicos e laboratoriais nestes dois grupos de doentes. Caracterizam 59 casos de doentes em idade pediátrica com PTI e 19 casos com LLA/LMA, seguidos na Unidade de Hematologia Infantil do Hospital de Dona Estefânia. Concluem não existir diferenças significativas entre as variáveis VPM e PDW entre os dois grupos de doentes. Com base nas três variáveis (VPM, PDW, PLAQ) foi construída uma regra de discriminação que fornece uma boa separação entre os grupos. Da caracterização clínico-laboratorial ressaltaram diferenças significativas entre as duas entidades nosológicas, o que permitiria prescindir a realização do mielograma para exclusão do diagnóstico de LLA/LMA numa criança com trombocitopénia significativa isolada.

Mutational Analysis of Portuguese Families with Multiple Endocrine Neoplasia Type 1 Reveals Large Germline Deletions

OBJECTIVE: To determine the spectrum of MEN1 mutations in Portuguese kindreds, and identify mutation-carriers. PATIENTS, DESIGN AND RESULTS: Six unrelated MEN1 families were studied for MEN1 gene mutations by single-strand conformational polymorphism (SSCP) and DNA sequence analysis of the coding region and exon-intron boundaries of the MEN1 gene. These methods identified 4 different heterozygous mutations in four families: two mutations are novel (mt 1539 delG and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and mt 1656 del C) all resulting in a premature stop codon. In the remaining two families, in whom no mutations or abnormal MEN1 transcripts were detected, segregation studies of the 5' intragenic marker D11S4946 and codon 418 polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene. Southern blot and tumour loss of heterozygosity analysis confirmed and refined the limits of these deletions, which spanned the MEN1 gene at least from: exon 7 to the 3' untranslated region, in one family, and the 5' polymorphic site D11S4946 to exon 9 (obliterating the initiation codon), in the other family. Twenty-six mutant-gene carriers were identified, 6 of which were asymptomatic. CONCLUSIONS: These results emphasize the importance of the detection of MEN1 germline deletions in patients who do not have mutations of the coding region. Important clues indicating the presence of such deletions may be obtained by segregation studies using the intragenic polymorphisms D11S4946 and at codon 418. The detection of these mutations will help in the genetic counselling of clinical management of the MEN1 families in Portugal.