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.

Fetal Anemia Causing Hydrops Fetalis From an Alpha-Globin Variant: Homozygous Hemoglobin Constant Spring.

BACKGROUND: Fetal anemia is often assumed to be due to red cell alloimmunization and Parvovirus infection, and can lead to hydrops fetalis and death in utero. Other causes, such as mutations of hemoglobin alpha, are less commonly considered. METHODS: We report 7 cases with fetal anemia causing hydrops fetalis. Serial Doppler ultrasound for measurement peak systolic velocity (PSV) of middle cerebral artery (MCA) was used for evaluation of fetal anemia. Fetal anemia is suggested if the MCA/PSV ratio is >1.5 multiple of median. Cordocentesis was performed subsequently to find the cause of fetal anemia and check fetal hemoglobin for consideration of intrauterine infusion. Investigations for fetal anemia include complete blood count, blood morphology, and blood group of mother and fetus, reticulocyte counts, red cell indices, screening for thalassemia, hemoglobin typing, acid elution test, parvovirus B 19 serology, and TORCH titer (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, and syphilis). Intrauterine infusion, using irradiated prestorage filtered red cell with hematocrit level of 80%, is indicated if fetal hemoglobin is <10 g/dL. RESULT: Seven cases with fetal anemia were prenatally diagnosed from gestational ages 20 to 34 weeks. Initial hematocrit in these cases varied from 9% to 17.2%. In each case, causes of anemia were determined using the investigations listed above. All cases underwent uneventfully up to 3 intrauterine transfusions. DNA study for thalassemia demonstrated homozygous Constant Spring (CS) in 5 cases, homozygous CS with heterozygous E in 1 case, and compound heterozygous CS and Pakse in 1 case. The perinatal outcomes were normal term in 5 cases, preterm in 2 cases. Low birth weight was determined in 2 cases. The screening for thalassemia major, including the osmotic fragility and dichlorophenol indophenol precipitation test (DCIP), is not helpful for detecting hemoglobin variants such as Constant Spring or Pakse. SUMMARY: This study emphasizes homozygous Constant Spring and compound heterozygous CS and Pakse as a cause of hydrops fetalis. Proper management for the fetus after diagnosis can lead to a good fetal outcome. Prevention control programs should include screening of parents for the heterozygous state.

Vitamin A supplementation for prevention of bronchopulmonary dysplasia in very-low-birth-weight premature Thai infants: a randomized trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one ofthe most significant complications among very-low-birth-weight (VLBW) premature infants. Vitamin A deficiency increases the risk of BPD in VLBWinfants. OBJECTIVE: To assess the effect of vitamin A supplementation for prevention of bronchopulmonary dysplasia in VLBW premature Thai infants. STUDY DESIGN: Randomized control trial. MATERIAL AND METHOD: Eighty premature infants weighing <1,500 g who received mechanical ventilation or oxygen supplementation at 24 hours ofage-admitted to Neonatal units ofSrinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand-were assigned to receive either intramuscular vitaminA 5, 000 IU3 times/week (treatment group) or sham procedure (control group) for four weeks. Serum vitamin A levels were measured before and after administration of the vitamin A. RESULTS: The baseline of mean serum vitamin A levels were similar in both groups. The mean serum level of vitamin A was significantly higher in the vitamin A supplemented infants than in the control infants on day 7 (1.41 +/- 0.48 vs. 0.92+0.38 pmol/ L, p<0.001), day 14 (1.48 +/- 0.90 vs. 0.96 +/- 0.36 micromol/L, p = 0.001) and day 28 (1.42 +/- 0.63 vs. 0.76 +/- 0.30 micromol/L, p<0.001) after vitamin A supplementation. None of the infants in the vitamin A supplemented group, compared to 5% of the infants in the control group, had vitamin A level <0.35 micromol/L, (indicating severe vitamin A deficiency) at 28 days. Fewer of the premature infants in the vitamin A supplemented group required oxygen supplementation at 36 weeks postmenstrual age than in the control group albeit not statistically significant (22.5 vs. 35% relative risk 0.71; 95% CI 0.40 +/- 1.26; p = 0.21). Supplementation with vitamin A was also associated with a significant reduction in the duration ofintubation (10.8 +/- 3.1 days vitamin A supplemented group vs. 26.1 +/- 6.4 days control group, p = 0.03), days on oxygen therapy (29.8 +/- 5.1 days vitamin A supplemented group vs. 58.2 +/- 9.1 days control group, p = 0.01) and length of hospital stay (61.9 +/- 4.2 days vitamin A supplemented group vs. 88.3 +/- 7.2 days control group, p = 0.002). CONCLUSION: The dose of vitamin A used in this study reduced biochemical evidence of vitamin A deficiency and, without complications, resulted in reducing duration of intubation, days of oxygen therapy, and length of hospital stay in premature infants suffering VLBW

Newborn screening for congenital hypothyroidism in Khon Kaen University Hospital, the first three years, a preliminary report.

Between January 2000 and December 2002, 9,558 of 10,868 live births at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, were screened for congenital hypothyroidism (CH). Dried blood spot thyroid stimulating hormone (TSH) was collected at age 48 hours or older. The cut-off TSH level for recall test was > 25 mu/L. Serum thyroxine (T4), Free T4 and TSH were performed during the confirmatory test. Six of 24 infants recalled for confirmatory thyroid function tests had abnormal tests. Primary CH was confirmed in 3 infants and thyroxine treatment was given. Two of the three infants had thyroid dysgenesis, one had normal thyroid gland. Three infants showed borderline CH from the confirmatory test, only one had borderline CH from the second confirmatory test and also received thyroxine treatment. Twenty infants with false positives during the screening and confirmatory tests were regularly followed-up for growth, development and thyroid function tests. The incidence of primary CH in this sole tertiary care government hospital in Northeast Thailand was 1:3,186. Routine newborn CH screening would ensure early detection and treatment.