Presentation of Compound Heterozygous Hemoglobin Constant Spring and Hemoglobin Pakse in Neonates.

BACKGROUND: Mutations causing α thalassemia are divided into deletion and nondeletion groups. In the nondeletion group, hemoglobin constant spring (Hb CS) and hemoglobin Pakse (Hb Pakse) are both caused by a termination codon mutation leading to elongation of the α2 globin gene. In the case of Hb CS, the mutation is TAA→CAA, whereas the mutation causing Hb Pakse is TAA→TAT. Clinical hematologic phenotypes are not significantly different. It is important to identify compound heterozygotes for purposes of genetic counseling. METHODS: We report 5 neonates with compound heterozygous Hb CS/Hb Pakse mutations with respect to clinical courses, hematologic profiles, and management. RESULTS: Among 5 cases (3 male babies and 2 female babies) with mean birth weight 2982 g (range, 2660 to 3440 g), 3 were diagnosed as compound heterozygous Hb CS/Hb Pakse, 1 as homozygous Hb E with compound heterozygous Hb CS/Hb Pakse, and 1 as heterozygous Hb E with compound heterozygous Hb CS/Hb Pakse. Clinical manifestations included fetal anemia (1 case), neonatal hyperbilirubinemia (5), neonatal anemia (2), hepatosplenomegaly (1), and cholestatic jaundice (1). Three cases required a single phototherapy; 2 cases needed double phototherapy for treatment of severe hyperbilirubinemia. During the first few months of life, all cases had mild anemia, slightly low mean corpuscular volume, wide red cell distribution width, and low red cell counts. At 1 to 3 years of age, all patients still had mild microcytic hypochromic anemia with Hb levels around 10 g/dL, increased reticulocyte count, and wide red cell distribution width. CONCLUSIONS: Misdiagnosis of Hb Pakse could occur via Hb typing using Hb electrophoresis, because the band comigrates with that of Hb CS. DNA study is the definitive method for diagnosis.

Clinical Course of Homozygous Hemoglobin Constant Spring in Pediatric Patients.

BACKGROUND: Hemoglobin (Hb) Constant Spring is an alpha-globin gene variant due to a mutation of the stop codon resulting in the elongation of the encoded polypeptide from 141 to 172 amino acid residues. Patients with homozygous Hb Constant Spring are usually mildly anemic. METHODS: We retrospectively describe clinical manifestations, diagnosis, laboratory investigations, treatment, and associated findings in pediatric patients with homozygous Hb Constant Spring followed-up at Srinagarind Hospital. RESULTS: Sixteen pediatric cases (5 males and 11 females) were diagnosed in utero (N=6) or postnatal (n=10). Eleven cases were diagnosed with homozygous Hb Constant Spring, 4 with homozygous Hb Constant Spring with heterozygous Hb E, and 1 with homozygous Hb Constant Spring with homozygous Hb E. Three cases were delivered preterm. Six patients had low birth weights. Clinical manifestations included fetal anemia in 6 cases, hepatomegaly in 1 case, hepatosplenomegaly in 2 cases, splenomegaly in 1 case. Twelve cases exhibited early neonatal jaundice, 9 of which required phototherapy. Six cases received red cell transfusions; 1 (3), >1 (3). After the first few months of life, almost all patients had mild microcytic hypochromic anemia and an increased reticulocyte count with a wide red cell distribution (RDW), but no longer required red cell transfusion. At 1 to 2 years of age, some patients still had mild microcytic hypochromic anemia and some had normocytic hypochromic anemia with Hb around 10 g/dL, increased reticulocyte count and wide RDW. Associated findings included hypothyroidism (2), congenital heart diseases (4), genitourinary abnormalities (3), gastrointestinal abnormalities (2), and developmental delay (1). SUMMARY: Pediatric patients with homozygous Hb Constant Spring developed severe anemia in utero and up to the age of 2 to 3 months postnatal, requiring blood transfusions. Subsequently, their anemia was mild with no evidence of hepatosplenomegaly. Their Hb level was above 9 g/dL with hypochromic microcytic blood pictures as well as wide RDW. Blood transfusions have not been necessary since then.

Maternal Serum Angiogenic Growth Factors in Intrauterine Growth Restriction versus Normal Pregnancies.

Objective: To assess maternal serum angiogenic growth factors level of soluble fms-like tyrosine kinase-1 (sFlt-1), placenta growth factor (PlGF) and sFlt-1/PlGF ratio among pregnant women with intrauterine growth restriction (IUGR) compared to those with normal pregnancies. Study design: A prospective cross-sectional study conducted at Srinagarind Hospital, Khon Kaen University, Thailand from July 2014 to April 2015. Material and Method: Twenty-one singleton pregnant women of gestational age between 26 to 39 weeks who had IUGR, and 21 normal pregnant women matched for gestational age were recruited. Descriptive statistics were used for demographic characteristics. Student t-test and Wilcoxon rank-sum test was used when appropriated to compare between the groups. Main outcome measures: Levels of sFlt-1 and PIGF and sFlt-1/PlGF ratio. Results: There were no statistical significant differences in gestational age, maternal age, parity status, maternal blood pressure level and hematocrit level between the groups. Median PlGF level among pregnant women with IUGR was significantly lower than that in control group (121 and 834.8 ng/ml respectively, p-value <0.01). The sFlt-1 level in pregnancies complicated by IUGR was slightly higher than that noted among normal pregnancies (2644 ng/ml and 2,136 ng/ml respectively, a p-value 0.105). The sFlt-1/PlGF ratio among pregnant women with IUGR was significant higher than that observed among normal pregnant women (34.1 and 2.6 respectively, p-value <0.01). Conclusion: Pregnancy with IUGR had low level of PlGF and high sFlt-1/PlGF ratio when compare with normal pregnancy.

Incidence, causes and pregnancy outcomes of hydrops fetalis at Srinagarind Hospital, 1996-2005: a 10-year review.

OBJECTIVE: To identify the incidence and determine causes and pregnancy outcomes of hydrops fetalis at Srinagarind Hospital. STUDY DESIGN: A retrospective descriptive study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University. MATERIAL AND METHOD: A retrospective medical record review of all pregnant women and newborns who were diagnosed with hydrops fetalis at all gestational ages and delivered at Srinagarind Hospital between 1996 and 2005. RESULTS: During the period of study, the incidence of hydrops fetalis was 1.80 per 1,000 total births (82 cases of 45,499 total births). Thirty-nine cases (47.56%) were idiopathic, 30 cases (36.58%) were Hb Bart's hydrops fetalis, and three (3.66%) cases were caused by congenital infection. The others 10 cases (12.19%) were achondrogenesis, Turner syndrome, twin-to-twin transfusion syndrome, severe anemia with unknown primary cause, cystic hygroma, multiple congenital anomalies, and Rh isoimmunization. The mortality rate of hydrops fetalis in the present series was 98.78%. One case, caused by Rh isoimmunization, survived. Maternal complications were 30 cases (36.59%) consisting of preeclampsia, preterm labor, disseminated intravascular coagulopathy, placenta previa, and postpartum hemorrhage. CONCLUSION: The incidence of hydrops fetalis was 1.80 per 1,000 total births. The common known cause was Hb Bart's hydrops fetalis. The mortality rate of hydrops fetalis in the present study was very high.

Prenatal prevention for severe thalassemia disease at Srinagarind Hospital.

OBJECTIVE: To evaluate the results and cost-effectiveness of prenatal prevention measurement in severe thalassemia diseases at Srinagarind Hospital. STUDY DESIGN: Descriptive study. SETTING: Antenatal care (ANC) Clinic, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. SUBJECTS: 1,498 thalassemic screened pregnant women first presenting at ANC Clinic at gestational age less than 17 weeks. MATERIAL AND METHOD: Medical records of thalassemic screened pregnant women between February 2002 and February 2005 were analyzed. Those with a value of mean corpuscular volume (MCV) less than 80 fl, or positive dichlorophenol indophenol precipitation test (KKU-DCIP Clear Reagent Kit) underwent hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) together with thalassemia investigation (complete blood count, MCV and Hb typing) of their husbands and to identify couples at risk of 3 severe thalassemia diseases; Hb Bart's hydrops fetalis, homozygous, -thalassemia and, -thalassemia/ Hb E disease. Then they were advised to undergo DNA analysis and, if they had fetal risk, appropriate prenatal diagnosis was offered. MAIN OUTCOME MEASURE: Number of affected fetuses detected by prenatal diagnosis. RESULTS: Nine hundred and ninety six pregnant women (66.49%) were positive on screening. Of these, 642 (64.46%) had thalassemia investigation done with their spouses. There were 19 couples at risk (1.27% of total screened pregnant women) for having fetal severe thalassemia disease from initial laboratory results. Most of them were, -thalassemia/ Hb E diseases. We found only 10 pregnant women (52.63%) that had undergone prenatal diagnosis. The consequent results were two affected fetuses (20%), one was Hb Bart's hydrops fetalis, and the other was, o-thalassemia/ Hb E disease. In these cases, their parents decided to discontinue the pregnancy. Our prevention program could save 1.14 million bahts for the cost of treatment in two prevented severe thalassemia cases. CONCLUSION: The prenatal prevention program of severe thalassemia disease at Srinagarind Hospital can effectively detect affected fetuses and reduce severe thalassemia disease, which is a major health problem in Thailand.