Nephronophthisis

Nephronophthisis is the name for a group of rare serious genetic diseases of the kidneys. The disease is an autosomal recessive form of tubulointerstitial nephritis. The nephronophthisis leads to cystic kidney at the corticomedullary border of the kidneys. To date, six different genes are known in which mutations or deletions can lead to nephronophthisis. The most common is the familiar juvenile nephronophthisis ( NPHP1 ).

Prevalence

The nephronophthisis is a rare hereditary disease. The prevalence of all six types of diseases together is about 1: 100,000. However, the data in the literature scatter considerably. This is due to the fact that the disease is quite rare and, secondly, that the diagnosis is difficult. There are estimates for the United States that 9 sufferers come to 8.3 million live births. In contrast, the estimates for Canada are at 1:50,000 live births. Male and female patients are equally affected by the disease.

Despite the relatively low frequency of nephronophthisis it is the most common genetic cause of end-stage renal failure in the first three decades of life.

Juvenile nephronophthisis ( NPHP1 )

The person responsible for the juvenile nephronophthisis NPHP1 gene is located on chromosome 2 gene locus in humans q13. Mutations or a gene deletion can lead to a widespread loss of function of the encoded gene from NPHP1 protein nephrocystin -1.

Initial symptoms of the disease arise by polyuria ( abnormally increased urinary excretion ) which usually occurs in 4 to 6 years of age. These children fall through excessive fluid intake at night ( polydipsia, pathologically increased thirst ) on. Since the symptoms are not very pronounced, the disease is usually diagnosed at an advanced stage of chronic renal failure. In an average age of 13 years it comes to end-stage renal failure, which reach all patients up to 25 years.

Infantile nephronophthisis ( NPHP2 )

The responsible for the disease NPHP2 gene is located on human chromosome 9 locus q22 - q31. Mutations or a gene deletion can lead to a widespread loss of function of the encoded protein gene from NPHP2 Inversin. The end-stage renal failure occurs in nephronophthisis type 2 usually before the age of one year, often even prenatally ( before birth), a.

Adolescent nephronophthisis ( NPHP3 )

The adolescent nephronophthisis has its origin on chromosome 3 gene locus q21 - q22. The end-stage renal failure occurs in an average age of 19, which is the case in comparison to NPHP1 and NPHP2 significantly later.

NPHP4, NPHP5, NPHP6, NPHP7

These four forms of nephronophthisis is as yet very little known. The nephronophthisis type 4 has its origin on chromosome 1 locus p36.22. The NPHP4 gene encoding the protein Nephroretinin. The NPHP5 gene, also called IQCB1, is located on chromosome 3 gene locus q21.1 and encodes nephrocystin - fifth NPHP6, also known as CEP290, is located on chromosome 12 locus q21.33. The only in 2007 discovered " NPHP7 gene " is the GLIS2 gene and encoding the zinc finger protein GLIS2.

Diagnosis

Patients with nephronophthisis have as a result of tubular concentrating defect considerable salt loss, which can lead to severe dehydration and electrolyte imbalance. The loss of the ability to concentrate the urine of more than 800 mOsm kg * - 1H2O, is an early symptom of the disease. In the blood of persons affected azotemia ( above average high content of nitrogen-containing metabolites ), anemia can (anemia ), demonstrate hypokalemia (potassium deficiency) and metabolic acidosis ( acidosis ). The poor kidney function may be detected by renal scintigraphy. The diagnosis is made by ultrasonography ( " ultrasound " ) or other imaging techniques such as magnetic resonance imaging, provide.

Atrophic tubules and cystic advanced are in the majority at the corticomedullary border of the kidneys. The cysts usually go out from the distal convoluted tubule and the collecting ducts.

Differentiation from medullary cystic kidney disease

Until the 1970s it is assumed that nephronophthisis and medullary cystic kidney disease, the two (Type 1 2) are the same disease. Both forms can not be distinguished histologically. The inheritance of nephronophthisis is an autosomal recessive trait, while it is autosomal dominant with MCKD1 and MCKD2. Because of the similarity of the disease is commonly known as NPH MCKD complex

Therapy

There is no treatment known to date, which could stop the deterioration of renal function to the chronic renal failure inside. The treatment of nephronophthisis is therefore carried out purely symptomatic. A cure has only a kidney transplant. With the terminal kidney failure renal replacement therapy is needed; either in the form of dialysis or by kidney transplantation.

In addition to the impaired renal function hyperuricemia and gout are still associated with the disease.