P. Chanprapaph

PRENATAL DIAGNOSIS OF β-THALASSEMIA MAJOR BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF HEMOGLOBINS IN FETAL BLOOD SAMPLES

In Thailand and adjacent countries, most of the β-thalassemia genes are β0-thalassemia mutations that prevent the production of Hb A. We propose the quantitation of the Hb A fraction in fetal blood in the mid-trimester of pregnancy by automated high performance liquid chromatography as a reasonable prenatal diagnostic method to be applied in areas with limited laboratory facilities. Forty pregnant women at risk of delivering a child with β-thalassemia major were identified using an erythrocyte osmotic fragility test and quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18–22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high performance liquid chromatography. The β-globin gene mutations were characterized by β-globin gene sequencing. The 4 bp deletion at codons 41/42 (−TTCT) was the most frequent of the 40 β-thalassemia mutations observed (20/40 = 50%), followed by the splice site mutation IVS-I-1 (G → T) (7/40 = 17.5%), the nonsense mutation at codon 17 (A → T) (7/40 = 17.5%), the nonsense mutation at codon 35 (C → A) (3/40 = 7.5%), and the β+ -thalassemia promoter mutation at −28 (A → G) (3/40 = 7.5%). High performance liquid chromatography revealed nine fetuses which had only Hb F and no Hb A. All were homozygotes or compound heterozygotes for β0-thalassemia mutations. In the remaining 31 fetuses, a Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a compound heterozygote for the −28 (A → G) and codons 41/42 (−TTCT) mutations. In the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of these, with a Hb A concentration of 1.82 ± 0.49% (range 0.8–2.8%), were β-thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 ± 1.47% (range 2.9–7.4%) and normal β-globin genes. The absence of Hb A in homozygotes or compound heterozygotes for β0-thalassemia mutations and the presence of measurable amounts of Hb A in heterozygotes and normal homozygotes, permits the diagnosis of fetuses expected to develop postnatal β-thalassemia major.

First trimester sonographic diagnosis of holoprosencephaly

Objective: To describe our experience with sonographic diagnosis of fetal holoprosencephaly in first trimester. Subjects: A total of three fetuses with early prenatal diagnosis of holoprosencephaly were sonographically evaluated and followed up. Results: The study revealed that all showed monoventricular cavity, fused thalami, no falx and cavum septum pellucidum. All of them were correctly diagnosed sonographically in the first trimester. Extracranial anomalies had also been identified in all three fetuses and all of them had facial abnormalities. Cytogenetic studies were successfully carried out in only one case. No polyhydramnios was demonstrated in all cases. Conclusion: This small series indicates that holoprosencephaly can be diagnosed in the first trimester. The most valuable clue to the diagnosis is the demonstration of the single ventricle.

Prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome.

The prenatal diagnosis of thrombocytopenia–absent‐radius (TAR) syndrome using ultrasound and cordocentesis in the 16th week of gestation is established. The sonographic findings detected in this case included bilateral absence of the radius and club hands with normal thumbs and metacarpals. Because of a high index of suspicion for the syndrome, cordocentesis for fetal blood analysis was performed. Thrombocytopenia, with a platelet count of 14 000/mm3, was identified. The pregnancy was electively terminated and subsequent findings confirmed the sonographic diagnosis. This report, to our knowledge, is one of a very limited number of cases published in the literature, in which the prenatal diagnosis of TAR syndrome was made.

Sonographic features of trisomy 13 at midpregnancy

Objectives: To evaluate the sonographic characteristics, at 16–22 weeks of gestation, of fetuses later diagnosed with trisomy 13. Methods: This descriptive analysis of a case series was conducted from June 1989 to May 2001 at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand. Women with abnormal sonographic findings at midpregnancy (16–22 weeks of gestation) underwent amniocentesis or cordocentesis for karyotyping, and the inclusion criterion was proven trisomy 13. Results: Indications for sonographic examination at midpregnancy were a genetic risk, large‐ or small‐for‐date fetus, and other suspected anomalies. Fifteen fetuses were later diagnosed with trisomy 13. In all of these cases there was at least one abnormal sonographic finding. In only one case did the fetus show no structural abnormality (at 17 weeks), but polyhydramnios and fetal growth restriction were observed. Common sonographic findings included holoprosencephaly with associated facial anomalies, and abnormal feet and/or hands, especially polydactyly. Non‐structural abnormal findings such as polyhydramnios or fetal growth restriction were seen in less than one third of the fetuses. Conclusions: Nearly all the fetuses with trisomy 13 had sonographic characteristics of abnormalities at midpregnancy although common findings had often not yet appeared or the findings were low‐sensitive. Detailed ultrasound at midpregnancy could effectively screen for further genetic testing pregnancies at risk for trisomy 13.

Prenatal Sonographic Findings Associated with Asphyxiating Thoracic Dystrophy (Jeune Syndrome)

Jeune syndrome, or asphyxiating thoracic dystrophy, is a rare autosomal recessive skeletal disorder characterized by a small thorax, short limbs, pelvic abnormalities (hypoplastic iliac wing), and renal anomalies. 1 Occasional abnormalities include polydactyly, pancreatic fibrosis, situs inversus, and deformed teeth. Renal abnormalities and renal failure are a significant feature and a hazard in later life. Most affected infants die within the first year of life from respiratory failure and infections; only a few affected children survive through early adulthood. Severe renal involvement may occur and lead to chronic renal insufficiency in patients who survive respiratory failure. 1,2 The disease was first described by Jeune and others in 1955; over 100 cases have now been reported. The frequency of Jeune syndrome is estimated to be between 1 in 100,000 and 1 in 130,000 live births. 2 Only a few cases were prenatally documented. 3-6 We report the prenatal diagnosis of Jeune syndrome at 26 weeks of gestation.

Prenatal Diagnosis of Isolated Anorectal Atresia with Colonic Perforation

We report here a case of prenatal diagnosis of isolated anorectal atresia with intrauterine colonic perforation at 34 weeks of gestation, characterized by the presence of a bilobed cystic pelvic mass with a V‐shape appearance separated from the bladder with changing features during observation. Mild ascites was also visualized. Other structures were normal on detailed ultrasound. The patient had spontaneously delivered a male infant weighing 2,100 g at 34 weeks of gestation. The infant died one day after birth, before surgical correction secondary to respiratory distress syndrome. Autopsy revealed isolated anorectal atresia, and high (supraelevator) lesions. In conclusion, the findings of bilobed cystic pelvic mass with a V‐shape were useful to diagnose anorectal atresia in this case. Prenatal ultrasound can facilitate early diagnosis and treatment.

Triple bubble sign: a marker of proximal jejunal atresia

Jejunoileal atresia occurs in one in 3000]5000 w x births 1 . Most believe that they are sporadic, acquired defects that result from a vascular insult andror ischemia during development. The incidence of associated extra-gastrointestinal malformations and chromosomal abnormalities are very low, although gastrointestinal anomalies are freŽ . quently present 45% of patients , including bowel malrotation, esophageal atresia, microcolon and intestinal duplication. Dilated loops of the small bowel, especially when accompanied by polyhydramnios, are the hallmark of small bowel obstruction. Prenatal diagnosis of small bowel obstruction has been made several times, mostly based on the finding of a double bubble sign of duodenal atresia and multiple fluid-filled bowel w x loops of jejuno-ileal atresia 2]4 , but a triple bubble sign as a marker of precise location of proximal jejunum obstruction has rarely been mentioned. A 20-year-old primigravida presented with pre-

Intrauterine intravenous transfusion therapy for hydrops fetalis due to anemia of uncertain causes

The treatment and prognosis of hydrops fetalis depend on the etiology or underlying fetal conditions. Intrauterine transfusions for fetal anemia can be effective in the selected cases [1,2]. Theoretically, anemia of unknown cause, after excluding common lethal problems such as Hb Bart’s disease, is probably justified for intrauterine transfusion. The purpose of the study was to demonstrate the possibility to reverse hydrops fetalis due to fetal anemia of unknown causes with intrauterine intravascular transfusion.