Hemoglobinopathies
The State Public Health Laboratory has been screening all infants
for hemoglobinopathies since April of 1989. The Newborn Screening
Laboratory uses a two-tiered screening system whereby all specimens
are tested using Isoelectric Focusing (IEF), which is electrophoresis
in a pH gradient. Any samples obtaining abnormal or questionable
results are re-assayed using the next level of testing which is
High Performance Liquid Chromatography (HPLC). These two methodologies
are highly complimentary in sensitivity and specificity, detecting
not only disease conditions, but also infants who are trait carriers.
Parents of infants with abnormal traits are offered genetic counseling
and no cost hemoglobin phenotype testing in order to ascertain if
they are at risk for having children with hemoglobinopathy disease
conditions in the future.
When a hemoglobinopathy condition is detected, the physician of
record is notified by the 2nd or 3rd day after the specimen was
received in the laboratory. Whole blood repeat testing on the infant
and parents is advised to confirm the disease and aid in diagnosing
the hemoglobinopathy. With sickle cell anemia, early detection is
followed up by prophylactic antibiotic treatment, which greatly
reduces deaths from bacteremia, pneumonia, and meningitis in these
children. Hemoglobinopathy resource centers are available for parent
counseling and continual observation of the child's health.
Hemoglobin Diseases
A group of autosomal recessive disorders characterized
by synthesis of abnormal hemoglobin molecules (e.g. S, C, D, &
E) or decreased synthesis of alpha or beta globin chains (thalassemia).
For a hemoglobinopathy disease condition to exist, an abnormal hemoglobin
or thalassemia typically must be inherited from both parents resulting
in a homozygous or double heterozygous condition. The most common
hemoglobinopathy in this country is Sickle Cell Disease. Infants
with Sickle Cell Disease conditions often have early overwhelming
sepsis and require prompt evaluation at a comprehensive care facility.
Parents of these infants are referred to Hemoglobinopathy Resource
Centers contracted by the Missouri Department of Health for treatment
and follow-up care.
| Prevalence (MO): |
1:400 (Sickle cell disease in African-Americans) |
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1:3000 (General Population) |
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| Analytes Measured: |
Hemoglobin Fractions |
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Fetal (F), Adult (A), Sickle (S), C-Hemoglobin (C), |
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E-Hemoglobin (E), D-Hemoglobin (D). |
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| Reporting Ranges: |
FA = Normal |
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FS = Homozygous S or Sickle thalassemia |
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FSC = Sickle Hemoglobin-C disease |
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FSA = Sickle beta plus thalassemia |
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FSD = Sickle Hemoglobin-D disease |
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FSE = Sickle Hemoglobin-E disease |
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FC = Homozygous C or C - thalassemia |
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FCA = Hemoglobin-C beta plus thalassemia |
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FE = Homozygous E or E - thalassemia |
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FEA = Hemoglobin-E beta plus thalassemia |
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F only = Possible homozygous beta thalassemia |
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| Feeding Effect: |
None |
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| Timing Effect: |
None (unless transfusion is needed) |
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Note: Sample collection
after a transfusion with red blood cells invalidates hemoglobin
test results for a minimum of 90 days post transfusion. It
is recommended that a sample be collected prior to a transfusion,
if at all possible. If a baby has been transfused prior to
sample collection, note it on the collection form. |
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| Confirmation: |
Whole blood repeat samples collected from the infant and both
parents within two weeks. The Missouri State Lab can provide
blood collection kit and no-cost testing. |
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| Treatment: |
Prophylactic antibiotics |
Common Hemoglobin Traits
A trait condition (carrier state) exists when a person
inherits one normal hemoglobin gene and one abnormal gene. This
person is healthy under normal circumstances and often is not aware
they are carrying an abnormal hemoglobin. There is enough normal
hemoglobin present to offset the dysfunction of the abnormal hemoglobin
(there are some rare exceptions and extenuating circumstances where
trait carriers can have symptoms). Like other recessive traits,
hemoglobin traits may be passed along for many generations and not
cause disease in offspring until which time they are inherited from
both parents. Parents of infants who are found to have abnormal
traits are offered hemoglobin phenotype testing by the state Laboratory
and genetic counseling by the sickle cell program.
| Prevelance: |
1:12 (Sickle Cell trait in African-Americans) |
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1:30 (Hemoglobin C trait in African-Americans) |
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1:10 (Hemoglobin E trait in Southeast Asians) |
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1:10,000 (Hemoglobin D trait in Caucasians) |
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| Analytes Measured: |
Hemoglobin Fractions |
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Fetal (F), Adult (A), Sickle (S), C-Hemoglobin (C), |
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E-Hemoglobin (E), D-Hemoglobin (D). |
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| Reporting Ranges: |
FA = Normal |
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FAS = Sickle Cell Trait |
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FAC = Hemoglobin C Trait |
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FAE = Hemoglobin E Trait |
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FAD = Hemoglobin D Trait |
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| Feeding Effect: |
None |
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| Timing Effect: |
None (unless transfusion is needed) |
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| Confirmation: |
Recommend whole blood samples collected from parents to ascertain
risk for having a future child with a hemoglobinopathy condition.
The Missouri State Lab can provide blood collection kits and
no-cost testing. |
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| Treatment: |
None |
Hemoglobin Variants
In the course of screening all newborns for the presence
of the common abnormal hemoglobins, various other hemoglobin variants
are uncovered, most of which are by and large unidentified. There
are over 800 hemoglobin variants described in the literature at
present. The vast majority of these have little known clinical ramifications
and end up being merely incidental findings. Many are fetal hemoglobin
variants that fade away with the fetal hemoglobin by six months
of age and become undetectable. An exception to this is Bart's hemoglobin.
The presence of Bart's hemoglobin is indicative of alpha thalassemia
and can result in a mild microcytic anemia. A highly elevated Bart's
hemoglobin may be clinically significant, especially in Southeast
Asians.
Any concern for the rare symptomatic variant can be monitored through
clinical observations (anemia, jaundice, cyanosis) combined with
a CBC and reticulocyte count.
Parents of newborns found to have unidentified variants are offered
hemoglobin phenotype testing free of charge by the State Laboratory.
| Prevalence: |
1:1000 (Approximation) |
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| Analytes Measured: |
Hemoglobin Fractions |
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Fetal (F), Adult (A), Unidentified (X) |
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| Reporting Ranges: |
FA = Normal |
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FAX = Unidentified Trait |
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| Feeding Effect: |
None |
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| Timing Effect: |
None (unless transfusion is needed) |
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| Confirmation: |
Whole blood repeat testing on infant (at 4 months of age)
and parents is offered. Missouri State Lab can provide blood
collection kits and no-cost testing. |
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| Treatment: |
None |
Adult Screening Program
The adult testing program provides testing for parents
who have obtained abnormal hemoglobinopathy screening results on
their newborns. Since the screening of all Missouri's newborns for
abnormal hemoglobins did not begin until 1989, many of these parents
were unaware that they have an abnormal hemoglobin trait and could
possibly be at risk for having a child with a disease condition
in the future. The adult testing program also accepts whole blood
samples for confirmation or further investigation of abnormal hemoglobinopathy
test results obtained from other adult screening laboratories within
the state.
| Prevalence: |
1:400 (Sickle Cell Disease in African-Americans) |
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1:3000 (General Population) |
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|
| Analytes Measured: |
Hemoglobin Fractions: |
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Fetal (F), Adult (A & A2), Sickle (S), C-Hemoglobin (
C), |
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E-Hemoglobin (E), D-Hemoglobin (D), Unidentified |
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Hemoglobin (X). |
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| Reporting Ranges: |
A,A2 = Normal |
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A,S,A2 = Sickle Cell Trait |
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S,A,F,A2 = Sickle Beta Plus Thalassemia |
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S,F,A2 = Sickle Cell Disease or Sickle Thalassemia |
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A,C,A2 = Hemoglobin C Trait |
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C,A2 = Hemoglobin C Disease |
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S,C,A2 = Sickle Hemoglobin C Disease |
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A,X,A2 = Unidentified Hemoglobin Trait |
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