The condition is caused by a mutation of the LIPA gene, which is responsible for the gene coding of the lysosomal lipase protein (also called lysosomal acid lipase or LAL), which results in a loss of the proteins normal function. When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL doesnt function, cholesteryl esters and triglycerides build up in the liver, spleen and other organs. The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.Lysosomal acid lipase deficiencies occur when a person has defects (mutations) in both copies of the LIPA gene. Each parent of a person with LAL deficiency carries one copy of the defective LIPA gene. With every pregnancy, parents with a son or daughter affected by LAL deficiency have a 1 in 4 (25%) chance of having another affected child. A person born with defects in both LIPA genes is not able to produce adequate amounts of the LAL enzyme.
Instead, the glomeruli are damaged in an undefined manner, perhaps through the activation of neutrophils in response to ANCA. Type III RPGN may be isolated to the glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most cases of the latter, the systemic disease is an ANCA-associated vasculitis such as granulomatosis with polyangiitis, microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis. Treatment
Therapy consists of a combination of rituximab, corticosteroids, and cyclophosphamide, with a substitution of azathioprine for cyclophosphamide after a ninety-day initial period being another option. When remission is achieved, immunosuppressants are still used, usually corticosteroids with azathioprine or rituximab infusions. Epidemiology
The incidence rate of rapidly progressive glomerulonephritis is approximately 3.9 individuals per million. References
Further reading
Greenhall, George H. B.; Salama, Alan D. (2015-02-19). "What is new in the management of rapidly progressive glomerulonephritis?". Clinical Kidney Journal. 8 (2): 143–50. doi:10.1093/ckj/sfv008. ISSN 2048-8505. PMC 4370308. PMID 25815169. == External links ==