Description - Sickle Cell Disease refers to a group of genetic disorders characterized by the presence of sickle hemoglobin (HbS), anemia, and acute and chronic tissue injury secondary to blockage of blood flow by abnormally shaped red cells. Normal adult hemoglobin, hemoglobin A (HbA), is composed of two alpha globin chains and two beta globin chains. In HbS, the alpha chain is the same as in HbA, but the beta globin chain differs from the normal by the substitution of valine for glutamic acid at the sixth position. The most common type of sickle cell disease is sickle cell anemia in which the affected individual is homozygous for the beta globin gene. Other common forms of sickle cell disease include the inheritance of the beta gene and a gene for beta-thalassemia (HbS beta-thalassemia) or another abnormal beta globin gene. Examples of other abnormal conditions include HbSC disease, HbSD and HbSE disease. Sickle cell disease is an autosomal recessive disorder. Red blood cells of newborns have a predominance of fetal hemoglobin, which does not contain beta globin. For this reason, signs and symptoms of beta globin abnormalities are not usually apparent at birth, but become evident later after adult hemoglobin replaces fetal hemoglobin. Infants/persons with two abnormal beta globin genes have disease. Infants/persons with one abnormal beta globin gene are said to have a hemoglobin trait and are carriers for the disease. Universal newborn screening is the best, most reliable, and cost effective method for casting the broadest possible net to identify affected infants. The frequency of hemoglobinopathies varies among ethnic groups. Sickle hemoglobin is found in descendants of people from Africa , Italy , Greece , Turkey , Arabia , and India . In the U.S. sickle hemoglobin is encountered in whites and Hispanics as well as blacks. Hemoglobin C occurs in descendants of central and western Africans. Hemoglobin E is common in persons of South Asian ancestry. Thalassemia genes (alpha and beta) originated in Italy , Greece , Asia, and Africa.
Clinical Features - Affected infants may present with dactylitis, fever and overwhelming sepsis, chronic hemolytic anemia, jaundice, episodic vascular occlusive crises, hyposplenism, periodic splenic sequestration (which can be life threatening in a small child) and bone marrow sepsis.
Serious bacterial infections are a major cause of morbidity and mortality in patients with sickle cell disease. Causative organisms in early childhood infections include; H. pneumoniae, H. influenzae, N. meningitis, Salmonella, M. pneumoniae, S. aureus, and E. coli. Severe overwhelming septicemia and meningitis due to S. Pneumoniae is the most significant cause of death during childhood. Osteomyelitis and pneumonia, as well as other infections, can be difficult to treat and usually require in-patient hospital treatment.
In other hemoglobin diseases clinical features are influenced by the type of hemoglobin variant. Homozygous hemoglobin C or E show only mild hemolytic anemia; persons with thalassemias have microcytic hypochromic anemia and children with the severe forms have hemolysis and may be transfusion dependent.
Treatment - Overall and prompt medical management should be planned in consultation with a comprehensive sickle cell center or a pediatric hematologist. Antibiotic prophylaxis (oral penicillin) has been shown to prevent life-threatening pneumococcal infections in sickle cell disease patients. Infants with abnormal screening results should be seen and a repeat specimen taken at one month of age. Treatment should begin by two months of age. Treatment consists of prophylactic antibiotics, appropriate immunizations to prevent pneumococcal and Haemophilus influenzae infection, preventive medical management, and patient/family education and counseling. Specialized treatment services are offered statewide for patients who are found to have abnormal screening results for sickle cell disease.
Hemoglobin Traits - Most hemoglobin traits exhibit few or no clinical problems. The value of trait detection is the opportunity to: test other family members; identify couples at risk; and to provide genetic counseling.
Family Testing for Hemoglobinopathies - The IEM screening laboratory will perform isoelectric focusing and HPLC assay on all family members of a newborn identified with not normal results by the screening laboratory, to determine hemoglobin bands. A $15 fee for the entire family is to be paid to the Department of Health by money order or physician’s check (no personal checks).
Collect the specimens on repeat (IEM-1A) forms. Please include the name, sex, birth date and sample date along with the name, address and phone number of the physician receiving the results:
Mail the specimens to: (First Class Mail)
New Jersey Department of Health
Inborn Errors of Metabolism
P.O. Box 371
Trenton , NJ 08625-0371