Paroxysmal Nocturnal Hemoglobinuria :Predisposing factor for Leukemia

The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. However, this observation was later disproved. Hemolysis has been shown to occur throughout the day and is not actually paroxysmal, but the urine concentrated overnight produces the dramatic change in color.

This disease has been referred to as the great impersonator because of the variety of symptoms observed during the initial manifestation and course of paroxysmal nocturnal hemoglobinuria (PNH). The clinical syndrome can present in 3 types of symptoms including (1) an acquired intracorpuscular hemolytic anemia due to the abnormal susceptibility of the RBC membrane to the hemolytic activity of complement; (2) thromboses in large vessels, such as hepatic, abdominal, cerebral, and subdermal veins; and (3) a deficiency in hematopoiesis that may be mild or severe, such as pancytopenia in an aplastic anemia state. The triad of hemolytic anemia, pancytopenia, and thrombosis makes paroxysmal nocturnal hemoglobinuria (PNH) a truly unique clinical syndrome.Paroxysmal nocturnal hemoglobinuria (PNH) has been reclassified from purely an acquired hemolytic anemia due to a hematopoietic stem cell mutation defect. This change in concept was brought about by the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells.Paroxysmal nocturnal hemoglobinuria (PNH) has been reclassified from purely an acquired hemolytic anemia due to a hematopoietic stem cell mutation defect. This change in concept was brought about by the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells.The common denominator in the disease, a biochemical defect, appears to be a genetic mutation leading to the inability to synthesize the glycosyl-phosphatidylinositol (GPI) anchor that binds these proteins to cell membranes.

FANCONI SYNDROME: A predisposing factor for Leukemia

Fanconi syndrome is a renal syndrome of idiopathic origin and it is also characterized by poluria, polydipsia and dehydration.

Fanconi syndrome is due to various causes, some inherited and some acquired. The incidence of each of these conditions is different, although almost all of them are rather rare. The circumstances surrounding this disorder remains an object of debate. The major area affected is the proximal tubules.

Its been proposed that one of these mechanisms explains its pathogenesis

 The 3 main categories in which they can be classified are (1) alterations in the function of the carriers that transport substances across the luminal membrane, (2) disturbances in cellular energy metabolism, and (3) changes in permeability characteristics of the tubular membranes.

The pathogenesis has further been linked up with cystinosis in children.The disease is caused by the accumulation of cystine in renal tubule cells.

The clinical features that cause patients to seek medical care include polyuria, polydipsia, bouts of dehydration (sometimes associated with fever), bone deformities, and impaired growth. Less often, the reasons for investigation are laboratory findings such as proteinuria, hypokalemia, hypophosphatemia, and hyperchloremic metabolic acidosis.

Then remember that due to its effect on bone and kidney production of hormones, Leukemia and Anemia do occur.