Nephronophthisis

background

Nephronophthisis is an inherited form of progressive kidney disease that affects children. Nephronophthisis is characterized by a progressive destruction of kidney tissue that leads to anemia, which occurs when the level of red blood cells becomes too low; polyuria (frequent urination); polydipsia (excessive thirst); short stature; and eventually kidney failure. If the kidneys fail, waste products accumulate in the blood and the body. As kidney function decreases, symptoms are related to the inability to regulate water and electrolyte balances, to clear waste products from the body, and to promote red blood cell production. Lethargy, weakness, shortness of breath, and generalized swelling may occur.
Nephronophthisis, first described in 1951, is sometimes referred to as familial juvenile nephronophthisis (FJN) or autosomal recessive medullary cystic kidney disease. There are at least four types of nephronophthisis, all of which are associated with the production of large amounts of urine and bedwetting early in life. In type 1 (NPH1), kidney failure develops at about age 13. In type 2 (NPH2), kidney failure usually develops from one to three years of age. In type 3 (NPH3), kidney failure develops at about age 19, and in type 4 (NPH4), kidney failure develops in the teenage years. In addition, about 15% of people with nephronophthisis also experience renal-retinal dysplasia (visual impairment caused by degeneration of the retinas). NPH1 is the most commonly documented type, so this monograph focuses on NPH1.
NPH1 is caused by a mutation or defect in the NPHP1 gene. This gene provides instructions for making the nephrocystin protein, which is essential for normal kidney functioning. This protein serves as a docking protein that interacts with proteins of adherens junctions, which are protein complexes that occur at cell-to-cell junctions, and focal adhesions, which are large groups of cells that serve as a link between a cell and the cell's external environment. In the case of NPH2, the mutated gene INV encodes for inversin, which is normally closely associated with the cytoskeleton and which allows for cell movement. A mutated INV gene may impair the function of cilia, the structures that allow a cell to move around, thereby contributing to cyst development. For NPH3, there is a genetic mutation in the NPHP3 gene, which encodes the protein nephrocystin-3, whose function is unknown. For NPH4, there is a genetic mutation in the NPHP4 gene, which encodes for the nephroretinin protein, whose function is also unknown. All types of nephronophthisis are inherited, or passed down among family members, as an autosomal recessive trait, meaning that an individual must inherit two copies of the defective gene, one from each parent, for the disease to occur.
Nephronophthisis accounts for about 10-20% of chronic kidney failure cases in children and young adults. Both males and females are affected equally, as are all races. It is often discussed with medullary cystic kidney disease, a similar degenerative kidney disease. Both conditions are inherited diseases, with similar renal morphology, characterized by bilateral cysts and end-stage renal disease (ESRD). Medullary cystic kidney disease is a distinct condition inherited as an autosomal dominant trait, and it affects people later in life than nephronophthisis.
There is no known cure for nephronophthisis. Instead, treatment aims to reduce symptoms and prevent complications. Individuals with nephronophthisis generally survive until age 4-15. Cause of death is usually related to kidney failure. As kidney function decreases, symptoms are related to the inability to regulate water and electrolyte balances, to clear waste products from the body, and to promote red blood cell production. As waste products build up in the blood, loss of appetite, lethargy, and fatigue become apparent, and will progress to the point where mental function will decrease and coma may occur. Because the kidneys cannot address the rising acid load in the body, breathing becomes more rapid as the lungs try to buffer the acidity by blowing off carbon dioxide. Blood pressure may rise because of the excess fluid, and this fluid may be deposited in the lungs, causing heart failure.

Related Terms

Autosomal recessive medullary cystic kidney disease, cystic disease of the renal medulla, cysts of the renal medulla-congenital, familial juvenile hyperuricemic nephropathy, familial juvenile nephrophthisis, FJN, medullary cystic kidney disease, NPHP1, polycystic kidney disease-medullary type, renal-retinal dysplasia with medullary cystic disease, Senior-Loken syndrome, uromodulin-associated kidney disease.

types of the disease

General: Nephronophthisis is an inherited form of progressive kidney disease that affects children. Nephronophthisis is characterized by a progressive destruction of the kidney tissue that leads to anemia, or low levels of red blood cells; polyuria (frequent urination); polydipsia (excessive thirst); short stature; and eventually kidney failure. There are four types of nephronophthisis. Types 1 and 4 are known as juvenile nephronophthisis; these may have complications in organs other than the kidneys. Types 1, 2, and 4 are caused by mutations or defects in genes that provide instructions for making the protein nephrocystin, while type 3 is caused by mutation in a gene that provides instructions for making the protein inversin. Treatment aims to reduce symptoms and prevent complications. Individuals with nephronophthisis generally survive until age 4-15. Cause of death is usually related to kidney failure.
Nephronophthisis type 1: Type 1 nephronophthisis (NPH1) is marked by development of kidney failure by about age 13. Besides the general symptoms that occur in all types of nephronophthisis, symptoms specific to this type of the disease include underdevelopment or absence of the cerebellar vermis, the part of the brain responsible for coordination and balance leading to a loss of coordination and balance; coloboma (holes in the optic nerve); degeneration of the optic nerve; development of fibrous tissue in the liver; eye dysfunction; and bone abnormalities.
Nephronophthisis type 2: Type 2 nephronophthisis, also known as infantile nephronophthisis, is characterized by kidney failure and typically develops between ages one and three. All symptoms associated with this type are kidney related.
Nephronophthisis type 3: Type 3 nephronophthisis, also known as adolescent nephronophthisis, is characterized by kidney failure and tends to develop at about age 19. All symptoms associated with this type are kidney related.
Nephronophthisis type 4: Type 4 nephronophthisis (NPH4) is marked by the development of kidney failure during the teenage years. Similar to NPH1, NPH4 may include symptoms that do not involve the kidneys, including underdevelopment or absence of the cerebellar vermis, the part of the brain responsible for coordination and balance, leading to a loss of coordination and balance; coloboma (holes in the optic nerve); degeneration of the optic nerve; development of fibrous tissue in the liver; eye dysfunction; and bone abnormalities.