The most frequent hematological genetic disorder and one
that has a large geographic influence. Clinical signs are a result of
hemolysis by chronic anemia. Clinical features include hepatosplenomegaly,
bone deformations, and cardiac failure. Strict asepsis is needed.
α-thalassemia, β-thalassemia, and
Cooley Anemia (β-thalassemia homozygote).
Most frequently occurring genetic disorder, geographic
variability (for example, for α-thalassemia in general population:
Congo 60%, Laos 35%, Caribbean 30%, South Europe 10%, France
0.1% of the general population). Other geographical distributions include
Asia, Filipino, Mediterranean, Middle Eastern, and, less frequently,
Autosomal dominant except for major
thalassemia, which is autosomal recessive.
The disease affects synthesis of either α
(gene located at 16p13.33 to 16p13.11) or β chain (gene located at
11p15.5) of the hemoglobin.
Hemoglobin synthesis normally provides a just balance
between the three different chains α, β, and γ.
Thalassemia modifies this status and leads to an abnormal presence of β chain (hemoglobin H) and γ chain (hemoglobin Barts). Hemoglobin
(Hb) A is preponderant and so a child with α-thalassemia presents at
birth with abnormal HbH and Hb Barts levels. Those allow quantifying of the
severity of the thalassemia. Fetal hemoglobin, which disappears within a few
months after birth by substitution with HbA, will also be higher. This is a
quantitative deficit and clinical expression varies according to deficit. In
β-thalassemia HbA2 will be higher than normal but signs will appear
after a few months. Certitude diagnosis is obtain by high-performance liquid
chromatography (HPLC) of hemoglobin.
Varies with the severity of the disease.
α-thalassemia: Class 1 and class 2 (less than 50% deficit): few signs with anemia;
class 3: severe hemolytic anemia with erythroblastopenia, frequent
infection, an increased spleen size, and hemosiderosis. Cardiac failure can
occur as a consequence of chronic hemolysis. In class 4, generally fetal or
neonatal death with anasarca.
β-thalassemia: Other clinical features seen in this disease include major
hepatosplenomegaly, growth failure, unconjugated hyperbilirubinemia, and
bone marrow hyperplasia that lead to skeletal deformation (frontal bossing,
prominent maxilla). Transfusions are frequent with their own complications.
Folate deficiency is frequent.
Cooley Sideroblastic Anemia: First described by Thomas Benton Cooley, a Detroit
pediatrician-hematologist, who also first described thalassemia in a
definitive way. Also known as Thalassemia Major or Homozygous β-Thalassemia. The clinical include severe anemia detected first in
childhood, growth retardation, hepatosplenomegaly, and jaundice. Facial and
skeletal deformity develop later. Hyperferricemia and abundance of
siderocytes in peripheral blood after splenectomy have also been described.
Death occurs from hemochromatosis at a relatively young age because
of cardiac, hepatic, and endocrine dysfunction.
Evaluate severity of the disease
(clinical, history); anemia (clinical, hematocrit, spleen echography);
cardiac function (chest radiograph, ECG, echography). Laboratory
investigations should include hematocrit, hemoglobin, bilirubin, erythrocyte
volume, reticulocyte, HbH.
Strict asepsis is needed during
procedures. Difficult direct laryngoscopy can occur as a result of skull
malformation. Perioperative ...