17.4 Pathology

• Introduction
  
• Hemoglobinopathies
  • Quantitative hemoglobinopathies (thalassemias)
  • Structural hemoglobinopathies (sickle cell syndrome)
• Myelopathies
  • Panmyelopathies
• Blood clotting disorders
  • Thrombocytopenias
  • Hereditary coagulopathies
• Disorders of the lymph vessels
• Immunologic disorders
  • Catch22
  • Myasthenia gravis

Immunologic disorders

The bases of Immunologic disorders are defects of cell-mediated and/or humoral immunity. Today, using refined methods, various forms of single or combined immunodeficiencies can be diagnosed.

Catch22

The catch22 (DiGeorge) syndrome is probably the most frequent 22q11 microdeletion syndrome with an incidence of 1: 4000 to 1: 5000. DiGeorge, a physician in Philadelphia, was the first to describe it and he postulated that a disorder of the 3rd and 4th pharyngeal arches with the corresponding neural ridge material was involved. The cranial neural ridge cells form a large part of the mesenchymal cell material of the bones in the neck region, the connective tissue of the face, the pharyngeal pouches, the walls of the conotruncus (large vessels), the thymus and the parathyroid.
Consequently, affected children exhibit abnormal facial structure, hypoparathyroidism, thymus-aplasia and conotruncal cardiac defects or aortic arch anomalies, respectively.

Today, with the help of the FISH method these microdeletions can be displayed.
With the CATCH22 acronym one tries today to connect the spectrum of symptoms:

• C: Cardiac defect
• A: Abnormal face
• T: Thymus hypoplasia
• C: Cleft palate
• H: Hypocalcemia
• 22: 22q11 deletion

Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease with a neuromuscular stimulus transmission deficiency.
Patients with MG have a general fatigue with muscle weakness. The first symptoms appear mostly through a disturbance of the eye motor functions (ptosis and diplopia). The course of the disease is variable but generally progressive.
The basis of this disease is a production of antibodies directed against acetylcholine receptors (85%) or Muscarinic receptors (15%) of the neuro-muscular end plate. In many patients alterations of the thymus are found. 10% of the patients have a thymus tumor and 70% have hyperplastic changes, indicating an active immune response.