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Growth hormone deficiency caused by pituitary stalk interruption in Diamond-Blackfan anemia

2003; Elsevier BV; Volume: 142; Issue: 3 Linguagem: Inglês

10.1067/mpd.2003.57

1097-6833

Thierry Leblanc, Éliane Gluckman, Raja Brauner,

Cancer-related gene regulation

Diamond-Blackfan anemia (DBA) is characterized by a defect in the maturation of erythroid cells. More than half of patients have short adult height and malformations, which are significantly and independently associated with short stature at diagnosis and the absence of hypotrophy at birth.1Willig TN Niemeyer CM Leblanc T Tiemann C Robert A Budde J et al.Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anaemia patients. DBA group of Societé d’Hématologie et d’Immunologie Pédiatrique (SHIP-, Gesellshaft fur Padiatrische Onkologie und Hamatologie [GPOH], and the European Society for Pediatric Hematology and Immunology [ESPHI]).Pediatr Res. 1999; 46: 553-561Crossref PubMed Scopus (136) Google Scholar We report a patient in whom the association of thumb hypoplasia and central anemia diagnosed at 1.9 years suggested DBA. Fanconi anemia was ruled out by normal results for chromosome breakage and cell-cycle studies, and Parvovirus B19 infection by bone-marrow polymerase chain reaction. Screening for rps19 gene mutation was negative. Corticosteroid therapy for 3 months increased the patient's hemoglobin level from 47 to 144 g/L. His height was –3.5 SD at 2.5 years, with a low growth hormone peak after stimulation with glucagon (2.2 μg/L) and plasma insulin-like growth factor I (47 μg/L), but his plasma thyroxin and cortisol were normal. Magnetic resonance imaging showed pituitary stalk interruption, with no visible pituitary stalk, no normal posterior lobe hypersignal in the sella turcica, and a hyperintense nodule in the region of the infundibular recess of the third ventricle. Pituitary stalk interruption may be familial2Pinto G Netchine I Sobrier ML Brunelle F Souberbielle JC Brauner R Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.J Clin Endocrinol Metab. 1997; 82: 3450-3454PubMed Google Scholar and associated with Fanconi anemia,3Dupuis-Girod S Gluckman E Souberbielle JC Brauner R Growth hormone deficiency caused by pituitary stalk interruption in Fanconi's anaemia.J Pediatr. 2001; 138: 129-133Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar but its association with DBA has not been reported. Deletions in genes found in growth hormone deficiency do not seem to be implicated.2Pinto G Netchine I Sobrier ML Brunelle F Souberbielle JC Brauner R Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.J Clin Endocrinol Metab. 1997; 82: 3450-3454PubMed Google Scholar However, its frequent association with ophthalmic malformations suggests that genes influencing the development of the hypothalamic-pituitary region are involved. At least 3 loci are involved in DBA,4Gazda H Lipton JM Willig TN Ball S Niemeyer CM Tchernia G et al.Evidence for linkage for familial Blackfan-Diamond anaemia to chromosome 8p23.3-p22 and for non-19q non-8p disease.Blood. 2001; 97: 2145-2150Crossref PubMed Scopus (65) Google Scholar but only mutations within the rps19 gene, located at 19q13.2, have been reported in 25% of patients.5Willig TN Draptchinskaia I Dianzani I Ball S Niemeyer CM Ramenghi U et al.Mutations in ribosomal protein S19 and Diamond-Blackfan anaemia: wide variations in phenotypic expression.Blood. 1999; 94: 4294-4306PubMed Google Scholar The wide range of organ systems affected in DBA6Alter BP The bone marrow failure syndromes p 216.in: 4th ed. Hematology of infancy and childhood. WB Saunders, Philadelphia (PA)1993Google Scholar and in Fanconi anemia implicates their genes in embryogenesis. Both disorders are associated with an increased risk of malignancies. Measurements of growth hormone and magnetic resonance imaging are warranted in patients with DBA who show an unexplained decreased growth rate.