Myelodysplastic syndromes (MDS) are group of clonal diseases of the hematopoietic system characterized by ineffective hematopoiesis, dysmyelopoiesis, a high frequency karyotype abnormalities and the risk of transformation into acute leukemias. Cytopenic and dysplastic changes are not pathognomonic for MDS, and there are many diseases that can imitate MDS. According to various sources, clonal karyotypic abnormalities are present only in 20-60% of MDS. The diagnosis of MDS is not difficult if blasts or sideroblasts are present in the bone marrow, or there are chromosomal aberrations as evidence of clonal hematopoiesis. The diagnostic problem arises in cases of MDS without sideroblasts, with normal karyotype and/or bone marrow hypoplasia. Since 2012, the ELNet Working Group has proposed and subsequently supplemented guidelines for Flow Cytometry as a complementary diagnostic tool. The aim of the study was to compare the results of the FCM Wells score MDS with the results of the İPSS-R score MDS The study included 30 patients initially diagnosed with MDS . The classification was carried out according to the WHO Classification of MDS 2016: MDS SLD-6 (20%), MDS-MLD-5 (16.7%), MDS RS-MLD-2 (6.7%), MDS-EB1-9 (30%), MDS EB2-8(27%). According to the IPPS-R, patients were scored based on blasts, cytogenetic examination, hemoglobin/platelet/absolute neutrophil count and scored as very-low, low, intermediate, high, very-high. Using the Wells evaluation criteria, which takes into account cytometric analysis of the cells of the main myelopoiesis lines, changes were found in the compartment of granulocytes in 93%, monocytes in 40% and erythrocytes in 73% of cases. High scores on the Wells scale (> 4) were obtained in 89% of (8/9) MDS-EB1, 100%(8/8) MDS-EB2, 80% (4/5) MDS MLD patients, 17% (1/6) MDS –SLD, 50%(1/2) MDS RS-MLD. According to IPPS-R, MDS patients received a score <1.5 very low risk group include 50%(3/6) MDS –SLD, 20%(1/5) MDS-MLD, score > 1.5-3 - Low risk group include MDS –SLD 50%(3/ 6), MDS-MLD-80% (4/5), MDS RS-MLD 50% (1/2), MDS-EB1-78%(7/ 9), score > 3- 4.5-intermediate risk qroup got MDS-EB1 22%(2/ 9), MDS EB2- 25% (2/8), MDS RS-MLD- 50%(1/2), Score > 4.5 respectively high risk group got patients MDS –SLD- 17%(1/6), MDS EB2- 50%(4/8), Score > 6 very high risk group got MDS EB2- 25%(2/8). The Pearson's correlation coefficient (PCC) showed high correlation between İPSS-R and FCM Wells score was 0.83, p<0.002. In our study, the FCM score had a positive correlation with the IPSS-R prediction. Expanded analysis of the main compartments of the bone marrow (early precursors of myelopoiesis, the population of granulocytes and monocytes, erythrocytes) using the Wells scale as an additional tool improves the diagnosis and distinguish low-grade MDS from non-clonal cytopenias.
Objective: 17α-hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), characterized by hypertension and varying degrees of ambiguous genitalia and delayed puberty.The disease is associated with bi-allelic mutations in the CYP17A1 gene located on chromosome 10q24.3.We aimed to present clinical and genetic findings and follow-up and treatment outcomes of 17OHD patients.Methods: We evaluated six patients with 17OHD from five families at presentation and at follow up.Standard deviation score of all auxological measurements was calculated according to national data and karyotype status.CYP17A1 gene sequence alterations were investigated in all patients.Results: The mean (±standard deviation) age of patients at presentation and follow-up time was 14.6±4.2 and 5.0±2.7 years respectively.Five patients were referred to us because of delayed puberty and primary amenorrhea and four for hypertension.One novel single nucleotide insertion leading to frame shift and another novel variant occurring at an ultra rare position, leading to a missense change, are reported, both of which caused 17OHD deficiency.Steroid replacement was started.The three patients with 46,XY karyotype who were raised as females underwent gonadectomy.Osteoporosis was detected in five patients.Four patients needed antihypertensive treatment.Improvement in osteoporosis was noted with gonadal steroid replacement and supportive therapy.Conclusion: 17OHD, a rare cause of CAH, should be kept in mind in patients with pubertal delay and/or hypertension.Patients with 46,XY who are raised as females require gonadectomy.Due to late diagnosis, psychological problems, gender selection, hypertension and osteoporosis are important health problems affecting a high proportion of these patients.
Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with PROKR2 mutations.Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature.Two different, very rare PROKR2 missense alterations classified as pathogenic (NM_144773.4:c.518T>G; NP_658986.1:p. (Leu173Arg)) and likely pathogenic (NM_144773.4:c.254G>A; NP_658986.1:p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families.PROKR2 dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers.
