Carboxyhemoglobin Levels in Neonatal Immune Hemolytic Jaundice Treated with Intravenous Gammaglobulin

In order to examine the effect of intravenous immunoglobulin (IVIG) on the rate of hemolysis in immune hemolytic hyperbilirubinemia, we measured the carboxyhemoglobin levels of 5 newborn infants who were subjected to IVIG treatment. The pretreatment rate of hemolysis, in the 5 patients with isoimmune hemolytic jaundice (3 patients with Rh hemolytic disease of the newborn and 2 patients with ABO hemolytic disease of the newborn), as reflected by caboxyhemoglobin levels was higher than the rate of hemolysis in normal newborn infants. In 4 out of the 5 patients treated with IVIG, there was a rapid decline (> 30%) of carboxyhemoglobin levels, a pattern which was different from that observed in normal newborn infants with no hemolytic jaundice and in 3 untreated patients with ABO hemolytic disease of the newborn. None of the treated patients required an exchange transfusion. Our preliminary results support the theory that the attenuation of jaundice observed following IVIG treatment in patients with immune hemolytic hyperbilirubinemia is caused, at least in part, by the reduction in hemolysis.     

Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies

Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (--(SEA)/-alpha(4.2)). The blood smears of patients with homozygous G701D/G701D showed approximately 25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis.     

Neonatal hyperbilirubinemia associated with Southeast Asian ovalocytosis

We report, herein, an infant who is twin A of a dizygotic twin, with premature birth and both twins having hemoglobin (Hb) E heterozygosity. Twin A who had Southeast Asian ovalocytosis (SAO) developed neonatal jaundice at the age of 2 days and needed phototherapy at the age of 3 days. The microbilirubin level was rapidly rising up to 535.2 μmol/L (31.3 mg/dl) with the hematocrit value of 38% at the age of 4 days prior to exchange blood transfusion. Exchange blood transfusion was done by 220 ml of O, Rh positive packed red blood cell reconstituted with 180 ml of O, Rh positive fresh plasma to lower the bilirubin level. Twin A received phototherapy from about 8 hr prior to exchange blood transfusion until 3 days later. Twin B, who did not have SAO, developed neonatal hyperbilirubinemia and needed only phototherapy. Twin A received a deletion of 27 basepairs in the erythroid band 3 gene and Hb E heterozygosity from his father. Am. J. Hematol. 60:136–139, 1999. © 1999 Wiley-Liss, Inc.     

Red cell morphology and malaria anaemia in children with Southeast-Asian ovalocytosis band 3 in Papua New Guinea

Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua New Guinea, by detection of the SAO band 3 gene variant using the polymerase chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria ( P  = 0.42). SAO band 3 was detected in 8.2% (23/281) of α⁺-thalassaemia homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a normal α-globin genotype ( P  = 0.12). The most consistent feature of SAO band 3 on microscopy of thin blood films was red cells with two or more linear or irregularly-shaped pale regions. In children living in the community, these were present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals (specificity 99.1%). The presence of 20% ovalocytosis was a poorer indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological data were similar in SAO band 3 and normal children. However, in children with acute malaria, haemoglobin levels and red cell counts were significantly lower in SAO band 3 than normal children. The degree of ovalocytosis was lower in children with SAO band 3 during acute malaria, suggesting that a selective loss of ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.     

Incidence of neonatal hyperbilirubinemia: a population‐based prospective study in Pakistan

Objective To estimate the incidence of neonatal jaundice and hyperbilirubinemia in a poor urban community in Karachi, where 70% of births occur at home. Methods Home‐based pregnancy and newborn surveillance were conducted from September 2004 to July 2006 in a multi‐ethnic population by trained community health workers. Newborns were visited several times at scheduled intervals until 59 days of life; any baby with jaundice was referred to the local clinic. Clinical assessments of jaundice were assigned by a physician and recorded using an adapted Kramer scale. Blood for plasma bilirubin was obtained if parents consented. Results Of a birth cohort of 1690 young infants during the study period, 466 infants (27.6%) were referred to our centre with jaundice. Of these, 64% were 0‐6 days old. Bilirubin was measured in 125 of 466 (27%) jaundiced newborns. Overall detected rate of hyperbilirubinemia (bilirubin >5 mg/dl) among 1690 newborns was 39.7/1000 live births (95% CI 29.3–47.6). Rate of plasma bilirubin levels in the range of 15–20 mg/dl was 13/1000 live births (95% CI 7.6–18.4); levels >20 mg/dl were observed in 3.5/1000 live births (95% CI 0.4–5.5). The proportion of newborns with bilirubin ≥15 mg/dl was significantly higher among those assigned a Kramer score of 4–5 compared to those receiving a score of 1–3 (P‐value 0.00004). Conclusion A significant burden of untreated severe neonatal jaundice, causing potential neurological sequelae, exists in developing countries such as Pakistan. WHO guidelines are needed for screening and appropriate management of neonatal jaundice in developing countries.     

The Relation of Conjunctival Pallor to the Presence of Anemia

OBJECTIVE: To determine the value of conjunctival pallor in ruling in or ruling out the presence of severe anemia (hemoglobin 90 g/L) and to determine the interobserver agreement in assessing this sign. DESIGN: Patients were prospectively assessed for pallor by at least one of three observers. All observations were made without information of the patient's hemoglobin value or of another observer's assessment. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENTS: Three hundred and two medical and surgical inpatients. MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) calculated for conjunctival pallor present, borderline, and absent were as follows: pallor present, LR 4.49 (95% confidence interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers were 0.75 and 0.54. CONCLUSIONS: The presence of conjunctival pallor, without other information suggesting anemia, is reason enough to perform a hemoglobin determination. The absence of conjunctival pallor is not likely to be of use in ruling out severe anemia. With well-defined criteria, interobserver agreement is good to very good.     

Glucose-6-phosphate dehydrogenase deficiency in Thailand; its significance in the newborn

The prevalence of G6PD deficiency in Thai males ranges from 3-18% depending upon the geographic region. G6PD "Mahidol" (163 Gly --> Ser) is the most common variant found in the Thai population. Almost all affected Thai individuals are not anemic and are asymptomatic. Severe acute intravascular hemolysis is occasionally seen, for instance, in those cases who have a viral infection, bacterial infection or have been exposed to chemicals or drugs. In Thailand, diagnosis of G6PD deficiency is usually made only in symptomatic cases. Neonatal screening of G6PD deficiency is not practiced nationwide, though studies have been done in several institutes. The assessment of G6PD activity in the newborn is mostly in order to find out the cause of neonatal jaundice. In our experience and that of others. G6PD deficient newborns are more prone to develop neonatal jaundice which is, on its own, no more severe than jaundice from other causes. Kernicterus due to G6PD deficiency, though still seen, is now very rare. Awareness of the hazard of hyperbilirubinemia, whatever the cause, along with active management is needed to prevent the occurrence of kernicterus. Neonatal screening is useful to detect abnormalities in the newborn. Weighing of the cost and benefit of neonatal screening should be made and the families of patients should be offered proper education and counseling to help them understand their babies' condition.     

Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3.

Southeast Asian ovalocytosis (SAO) occurs at high frequency in malarious regions of the western Pacific and may afford a survival advantage against malaria. It is caused by a deletion of the erythrocyte membrane band 3 gene and the band 3 protein mediates the cytoadherence of parasitized erythrocytes in vitro. The SAO band 3 variant may prevent cerebral malaria but it exacerbates malaria anemia and may also increase acidosis, a major determinant of mortality in malaria. We undertook a case-control study of children admitted to hospital in a malarious region of Papua New Guinea. The SAO band 3, detected by the polymerase chain reaction, was present in 0 of 68 children with cerebral malaria compared with six (8.8%) of 68 matched community controls (odds ratio = 0, 95% confidence interval = 0-0.85). Median hemoglobin levels were 1.2 g/dl lower in malaria cases with SAO than in controls (P = 0.035) but acidosis was not affected. The remarkable protection that SAO band 3 affords against cerebral malaria may offer a valuable approach to a better understanding of the mechanisms of adherence of parasitized erythrocytes to vascular endothelium, and thus of the pathogenesis of cerebral malaria.     

Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency

We report the first successful use of BMT for the treatment of RBC pyruvate kinase (PK) deficiency in a boy who developed neonatal jaundice and severe transfusion-dependent hemolytic anemia a few months after birth. He received a BMT at the age of 5 from an HLA-identical sister who has normal PK activity after conditioning with busulfan and cyclophosphamide. The post-transplant course was uneventful. At present, 3 years after transplant, he is 8 years old and has a normal hemoglobin level and normal RBC PK activity without evidence of hemolysis. DNA analysis has confirmed full engraftment.     

G6PD deficiency with hemolytic anemia due to a rare gene deletion--a report of the first case in Malaysia

A 2-year-old Chinese boy was referred to Hospital UKM for investigation of recurrent episodes of dark-coloured urine and pallor since birth. He was born prematurely at 34 weeks gestation and developed severe early-onset neonatal jaundice requiring exchange blood transfusion. Screening at birth showed Glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination revealed pallor, jaundice and mild hepatomegaly. Results of laboratory investigations showed a hemoglobin level of 11.0 g/dl with a hemolytic blood picture, reticulocytosis of 20% and red cell G6PD activity reported as undetectable. The patient's DNA was analysed for G6PD mutations by PCR-based techniques and DNA sequencing and results showed a 24 bp deletion of nucleotide 953-976 in the exon 9 of the G6PD gene. DNA analysis was also performed on blood samples of the patient's mother and female sibling confirming their heterozygous status, although both showed normal red cell G6PD activity levels. The patient was discharged well and his parents were appropriately advised on the condition and the importance of taking folic acid regularly. This is a first case report in Malaysia of G6PD deficiency causing chronic-hemolytic anemia. The rare 24 bp deletion causes the G6PD Nara variant, previously reported only in two other unrelated males, a Japanese and a Portuguese both with chronic hemolytic anemia.     

Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease.

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta-thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions.     

Studies on hemolytic anemia in pregnancy with evidence for autoimmunization in a patient with a negative direct antiglobulin (coombs') test

Three patients were studied who had acquired hemolytic anemia during pregnancy. One patient had a relapsing hemolytic anemia of pregnancy with a negative direct antiglobulin test. Previously reported cases have been presumed to be antibody-mediated because of rapid destruction of transfused blood, transient hemolysis in the newborn, and a favorable response to corticosteroid therapy. Our findings with the complement-fixation antibody consumption (CFAC) test offer support for an immune pathogenesis, since we documented abnormal concentrations of IgG on the patient's red cells during pregnancy and also on a sample of cord blood. The hemolytic anemia responded partially to prednisone during pregnancy and resolved postpartum. A repeat CFAC test postpartum revealed a marked reduction in the number of IgG molecules per red cell on the mother's cells, and IgG was no longer detectable on the infant's red cells. The other patients had serologic abnormalities characteristic of an autoimmune hemolytic anemia with an IgG warm autoantibody. The patients were followed closely during pregnancy because of previous reports of life-threatening morbidity in mothers, as well as stillbirths, neonatal death, and seriously affected infants. An amniocentesis was performed in one patient because of persistent hemolysis in spite of prednisone therapy. The mothers and their infants did well, but serologic abnormalities and mild hemolytic anemia persisted in both mothers. Therefore, an elective splenectomy was performed with significant improvement in both instances.     

Low glucose-6-phosphate dehydrogenase enzyme activity level at the time of hemolysis in a male neonate with the African type of deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) levels are not usually drawn in the evaluation of black neonates with hyperbilirubinemia because of the oft-stated opinion that the levels may be normal at the time of hemolysis and thus will be misleading. In fact, this opinion is not applicable to newborns as many studies have shown that deficiency in the conjugating ability of the liver, not hemolysis, is the main cause of neonatal jaundice associated with G6PD deficiency. We present a case report of a neonate with brisk hemolysis and hyperbilirubinemia in whom the G6PD level was abnormally low at the time of the hemolytic episode. DNA analysis showed him to have the A-(202A,376G) variant and, as well, the UGT1A1 promoter repeat polymorphism associated with Gilbert's disease. This case, as well as a review of the literature, indicates that enzyme levels are not normal in patients with G6PD A- who are undergoing hemolysis.     

Mild hemolysis in a girl with G6PD Sumaré (class I variant) associated with G6PD A-

In the present study we describe the clinical and laboratory features of a female child, a compound heterozygote for glucose-6-phosphate dehydrogenase (G6PD) Sumaré (1292T-->G) and African variants (202G-->A). G6PD Sumaré is a variant causing chronic nonspherocytic hemolytic anemia. The child had neonatal jaundice 2 days after birth and needed phototherapy for 8 days. Since then, she has not had episodes of dark urine or new episodes of jaundice. She has not had hemolytic crises in spite of five respiratory infections and antibiotics administration. Laboratory data showed a reticulocytosis (5.6%) without anemia and serum unconjugated bilirubin at the upper limit of the normalcy. No hemoglobin and hemosiderin in the urine were detected. G6PD activity at 37 degrees C was 1.15 UI/g Hb and G6PD cellulose acetate electrophoresis at pH 9.0 revealed two bands, in equal amounts, with normal and faster migration, respectively. She was homozygous for the normal (TA)6(TA)6 repeat in the UGT1A1 promoter. We conclude that the association of G6PD Sumaré and G6PD A- gave rise to a very mild chronic hemolysis, and the red cell population containing G6PD A- is probably enough to protect against severe chronic hemolysis.     

2013年南京及周边地区新生儿溶血病统计分析

目的:了解2013年南京市区、郊区及周边地区新生儿溶血病发病情况。方法:对2013年南京市区、郊区及周边地区14家医院送检的1 430例疑似新生儿溶血病的血液标本检测结果进行分析。结果:1 430例标本主要来源于南京市区3家医院,其次为郊区及周边地区。新生儿溶血病总的阳性率为33.3%,市区医院阳性率低于郊区及周边地区。新生儿溶血病主要以ABO血型系统溶血为主,南京市区3家医院溶血血型系统种类较多;ABO血型系统溶血阳性标本中,母亲血清抗体效价1∶64的占29.4%,其中周边地区的比例最高。另有检出13例C3d阳性标本。结论:新生儿溶血病是一种免疫性溶血性疾病,当新生儿出现黄疸症状或母子血型不合但未出现黄疸时,应及时送检,及早确定是否是新生儿溶血病,达到早发现早治疗的目的,对于新生儿生存以及生长发育有益无害。     

高胆红素血症新生儿先天性巨细胞病毒感染检测

目的了解高胆红素血症新生儿巨细胞病毒(HCMV)感染情况并分析其意义。方法对170例高胆红素血症新生儿血清标本检测抗HCMV-IgG和IgM及血清总胆红素(TBIL),以排除高胆红素血症新生儿(100例)血清为正常对照;对筛查HCMV-IgM阳性的标本进一步分析DNA含量。结果高胆红素血症患者血清HCMV-IgG、IgM阳性率分别为57.6%和13.5%,正常对照组为42.0%和3.0%,差异均有统计学意义(P<均0.05);单个核细胞DNA阳性率86.9%,血浆游离DNA阳性率13%,差异有统计学意义。结论 HCMV感染与新生儿高胆红素血症相关性大,可能是引起高胆红素血症的主要病原之一;且HCMV DNA主要分布于单个核细胞中。     

Exchange Transfusion for Severe Neonatal Hyperbilirubinemia: 17 Years’ Experience from Vojvodina,Serbia

This study aimed to evaluate the frequency of the main risk factors for severe neonatal hyperbilirubinemia, to determine the incidence of exchange transfusion (ET) in the Autonomous Province of Vojvodina (the northern part of Serbia) and to describe the experience with ET performed in premature and term infants during the past 17 years. We performed a retrospective data analysis of 398 newborn infants who underwent a double volume ET from 1997 to 2013. During the 17 year study period, a decreasing incidence of ET, expressed per thousand newborns, was observed. A total of 468 double volume ET were performed: 328 (82.4 %) infants had one treatment and 70 (17.6 %) had repeated treatments. A total of 262,830 mLs of blood were transfused, an average of 660 mLs per child. There were 221 male and 177 female infants, with a sex ratio 1.25:1. The frequencies of risk factors for developing hyperbilirubinemia were as follows: (1) 38 % RhD incompatibility; (2) 38 % ABO incompatibility (26 % group A infant of group O mother, 12 % group B infant of group O mother); (3) 7 % low birth weight/preterm birth; (4) 17 % other factors. Risk factors for neurotoxicity were identified in 56.3 % of infants. No deaths or complications were reported arising from the treatment. ABO and Rh incompatibilities were found to be the main risk factors for severe neonatal hyperbilirubinemia in Vojvodina. Exchange transfusion, used as therapy for severe hyperbilirubinemia, trended downwards over the period of this study.     

Hereditary nonspherocytic hemolytic disease; a study of a singular familial hemolytic syndrome

Extensive studies were performed on four cases from three unrelated kindredswith a familial hemolytic syndrome not associated with any significant red cellanomaly (hereditary nonspherocytic hemolytic disease). These cases were compared with similar ones already reported in the literature.

1. Hereditary nonspherocytic hemolytic disease appears to be transmitted asa Mendelian dominant. Frequently the gene responsible for the condition seemsto have low expressivity. In some cases, the hereditary mechanism may be dueto inheritance of a recessive gene from each parent. The basic erythrocytic defectresponsible for the condition is unknown. In view of various clinical and hematologic findings, it is likely that hereditary nonspherocytic hemolytic disease maybe a group of diseases involving more than one mechanism.

2. All criteria of hemolytic anemia (erythroid hyperplasia of the bone marrow,reticulocytosis, hyperbilirubinemia, increased fecal urobilinogen, rapid turnoverof tracer iron in the plasma) were satisfied.

3. Red cell survival time studies revealed an intraerythrocytic defect with amean life span of twelve to seventeen days. Normal red cells transfused into thepatients under study survived normally. Anemia was normochromic and normocytic or macrocytic; it varied from mild to severe.

4. Osmotic and mechanical fragility of the red cells was normal. Osmotic andmechanical fragility tests after incubation at 37 C. for 24 hours in some showed amild increase compared with normal controls. Autohemolysis of incubated oxalated blood was not marked and varied from case to case.

5. The electrophoretic mobility of hemoglobin from the patients was that ofnormal adult hemoglobin. Small increases of fetal hemoglobin were seen in several cases.

6. In contrast to the histologic findings in hereditary spherocytosis the splenicpulp was not congested, but hemosiderin deposits were heavy. Liver biopsy specimens showed deposits of hemosiderin in parenchymal and Kupffer cells.

7. Splenectomy did not arrest the hemolytic process. Mild improvement was seenin one case. In most cases the operation is of no value.

8. Diagnostic difficulties may be encountered with mild cases of hereditaryspherocytosis. Examination of rouleaux in fresh blood and an osmotic fragilitytest in 0.65 per cent sodium chloride after incubation usually establishes the differential diagnosis. The condition may present clinically as hemolytic disease ofthe newborn and must be differentiated from erythroblastosis due to Rh or otherblood group incompatibilities. Other hereditary hemolytic diseases such assickle cell anemia, Cooley’s anemia, hereditary spherocytosis, and hereditaryhemolytic elliptocytosis are easily ruled out by their typical clinical and hematologic manifestations. When a family study is negative or cannot be done, a redcell survival time determination may be necessary to rule out acquired hemolyticanemia with a negative Coombs test. Some cases that have been diagnosed asconstitutional hyperbilirubinemia (familial nonhemolytic jaundice) may actuallyrepresent mild hereditary nonspherocytic hemolytic disease.

Submitted on October 7, 1953 Accepted on November 3, 1953     

The Lea Antigen and Neonatal Hyperbilirubinemia in Taiwan

Neonatal jaundice is known to be more severe in Taiwanese infants than in Caucasian infants. Although ABO fetomaternal incompatibility and glucose-6-phosphate dehydrogenase deficiency have been shown to play a role in the etiology of neonatal jaundice in some Taiwanese infants, the etiology in the majority of cases is unknown. In this study we found that in Taiwanese newborn infants, the red cell Le^a antigen appeared later in infants who were jaundiced (peak serum bilirubin levels of >12 mg/dl during the first week of life) than in infants who were not. However, the Le^b antigen, and hence the transferases encoded by the Se and Se ^w genes, did not appear to be similarly involved in the etiology of physiological jaundice. Thus it would appear that the Le gene-specified transferase is less active or has a delayed function, in jaundiced infants. The relationship between the Le gene-specified transferase and bilirubin has yet to be established.     

The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma+-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma+-thalassemia is responsible for neonatal hemolytic anemia in this family.