Definition
Cooley's disease is a form of hereditary thalassemia, caused by a reduced or absent synthesis of beta-globin hemoglobin chains. The result is a picture of post-natal onset anemia, early destruction of red blood cells (hemolysis) and ineffective erythropoiesis of varying severity.
This haematological disorder is due to very heterogeneous alterations (point or compound mutations, deletions, etc.) of the HBB gene (11p15.5). Transmission is autosomal recessive, so only a child whose parents are carriers can be affected by Cooley's disease.
Cooley's disease presents very variable clinical pictures, which depend on the severity of the genetic defect (from severe anemia to an almost asymptomatic condition).
Most common symptoms and signs *
- Anemia
- anisocytosis
- Anorexia
- Arrhythmia
- Asthenia
- Cachexia
- dizziness
- Cardiomegaly
- palpitations
- Diarrhea
- Abdominal distention
- Abdominal pain
- Pain in the upper part of the abdomen
- Hepatomegaly
- Temperature
- Bone fractures
- insulin Resistance
- hypersplenism
- Hypoxia
- Jaundice
- Dental malocclusion
- Pallor
- Growth delay
- Drowsiness
- splenomegaly
- Skin Ulcers
Further indications
In general, the disorder begins very early: in the first months of life, the child suffering from the disease manifests progressive pallor, substationo and hepatosplenomegaly.
Subsequently, Cooley's disease involves systemic symptoms, such as anorexia, decay of general conditions and recurrent fever attacks. If the patient is not treated with transfusions, signs of anemia with intra-medullary hemolysis appear.
Characteristics of Cooley's disease are bone alterations, which manifest themselves with thickening of the bones of the skull, malar eminences (protruding cheekbones), knee valgus and pathological fractures of the long bones.
In the context of this haematological disorder, food problems (lack of appetite), muscle weakness, diarrhea, irritability, progressive distension of the abdomen (secondary to splenomegaly and hepatomegaly) and typical cranio-facial anomalies (epicanthus, protrusion and hypertrophy) may also occur. maxillary with internalization of the teeth, depression of the nasal bridge, etc.).
In the context of Cooley's disease, endocrine disorders (including hypothyroidism, parathyroid and adrenal insufficiency, diabetes mellitus and osteoporosis), cholelithiasis (such as in sickle-cell anemia) and skin ulcers in the lower limbs due to chronic venous insufficiency can be observed.
In the case of regular transfusions, growth and development tend to be normal, although there may be complications from iron overload, such as delay in body development and sexual maturation. Over time, the increased absorption of iron associated with transfusion support determines the picture of hemochromatosis. At cardiac level, this can cause pulmonary hypertension, arrhythmias, dilated myocardiopathy and heart failure. Instead, hepatic siderosis can lead to functional insufficiency, fibrosis and cirrhosis.
The suspicion of the disease can arise with a visit after birth, due to the appearance of a suggestive symptomatology, such as jaundice and poor growth, or the finding of a microcytic hemolytic anemia. The diagnosis of Cooley's disease is confirmed by biochemical analyzes (hemochromocytometric and hemoglobin electrophoresis) and genetic tests. In addition, haemolytic signs of ineffective erythropoiesis are always found, with indirect hyperbilirubinemia, hypersideremia and hyperferritinemia. In pregnancies at risk, prenatal diagnosis of Cooley's disease on chorionic or amniocentesis villi is possible.
Treatment includes several approaches, including blood transfusions associated with chelation therapy (to prevent iron accumulation), splenectomy (if the disease causes severe anemia or splenomegaly) and bone marrow or stem cell transplantation from compatible donors. If neglected, the severe anemic state leads to early childhood death from infections and cachexia.
