Malformations, syndromes and diseases

Malformations, syndromes and diseases

Histology

Connective tissue

Osteogenesis imperfecta: (collagen defect) autosomal dominant mutation of collagen genes (COL1A1 or COL1A2). It results in bones that break easily (*1).

Kniest dysplasia: Is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing. It is caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen.

Ehlers-Danlos syndrome: Is a group of genetic connective tissue disorders. It may be caused by mutations in the following genes: Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB. Enzymes: ADAMTS2, PLOD1, B4GALT7, DSE, and D4ST1/CHST14. Symptoms can vary from mildly loose joints to life-threatening complications such as aortic dissection. Chronic pain or early osteoarthritis may also occur.

Marfan's syndrome: Leads to a severe arterial impairment and high risk of aortic aneurysm, is due to fibrillin genetic anomaly.

Bone

Osteogenesis imperfecta: Genetic disorder with defective collagen production leads to fragile bone (*1).

Osteomalacia: (mineralization defect) softening of the bones due to a lack of vitamin D or a problem with the body's ability to break down and use this vitamin. This results in defective mineralization and bone softening.

Osteoporosis: Osteoclasts are more active than osteoblasts, resulting in a decrease of bone mass, with normal bone mineralization and microstructure.

Paget disease: Chronic disorder that can result in enlarged and misshapen bones. Paget's is caused by the excessive breakdown and formation of bone, followed by disorganized bone remodeling. This causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones.

Blood

Red blood cell (RBC) disorder

Anemias: Low oxygen transport capacity of the blood, red blood cell low count or hemoglobin deficiency:

• Aplastic anemia - Inability of the bone marrow to produce blood cells
• Blood loss anemia
• Hemolytic anemia
• Pernicious anemia - Impaired vitamin B12 absorption
• Iron deficiency anemia - Blood loss, RBC small and lighter color

Microcytosis/Macrocytosis: Dimension

Anisocytosis: Different dimension

Poikilocytosis: Abnormally shaped

Howell–Jolly bodies: Basophilic nuclear remnants

Membrane defects

• Cytoskeleton protein defects: Ankyrin, spectrin, protein 4.1, protein 4.2
• Membrane defect: Band 3.
• Spherocytosis: Loss of connection between membrane and cytoskeleton
• Elliptocytosis: RBC are elliptical. Many defects can result in elliptocytosis. It is a disease related to the impaired ability of erythrocyte to get back to original shape after transit in small capillaries. Hemolysis is well compensated. MCV is not reduced, MCHC is not increased. No reduced osmotic resistance. Often there is no need of therapy. In few cases splenectomy is sufficient.
• Ovalocytosis: RBC are elliptical.
• Stomatocytosis: Permeability disorder (protein 7.2). Reduced MCHC and increased MCV. Hemolysis is well compensated. Reduced osmotic resistance. Often there is no need of therapy.