Nephronophthisis
Encyclopedia
Nephronophthisis is a genetic disorder
of the kidneys which affects children. It is classified as a medullary cystic kidney disease
.
The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.
It is a form of ciliopathy
.
Its incidence has been estimated to be 0.9 per million people in the United States, and 1 in 50.000 births in Canada.
(production of large volume of urine), polydipsia
(excessive liquid intake), and mild proteinuria
(the abnormal appearance of protein in the urine), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis
or a kidney transplant in order to survive.
Approximately 10% of individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include blindness, liver problems, severe global developmental delay or mental retardation, and neurologic involvement in which the cerebellum
is affected.
From sequencing the DNA
of individuals and families with nephronophthisis, scientists have identified thus far 8 different genes in which mutations can cause the disease. These genes are called NPHP1
, NPHP2, NPHP3
, NPHP4
, NPHP5, NPHP6, NPHP7, and NPHP8, and the proteins for which they encode are known as the nephrocystins. Although the biological function of these proteins is not yet known, they all localize at least in part to an organelle
in the cell
called the primary cilia.
s, both genetic syndromes
and genetic diseases
, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical
root cause of the widely-varying, phenotypically
-observed disorders. Thus, Nephronophthisis is a ciliopathy
. Other known ciliopathies include primary ciliary dyskinesia
, Bardet-Biedl syndrome
, polycystic kidney
and liver disease
, Alstrom syndrome
, Meckel-Gruber syndrome and some forms of retinal degeneration
.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of the kidneys which affects children. It is classified as a medullary cystic kidney disease
Medullary cystic kidney disease
Medullary cystic kidney disease is an autosomal dominant kidney disorder characterized by cysts in both kidneys and tubulointerstitial sclerosis leading to end-stage renal disease...
.
The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.
It is a form of ciliopathy
Ciliopathy
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosomes, it is possible for ciliopathies to be associated...
.
Its incidence has been estimated to be 0.9 per million people in the United States, and 1 in 50.000 births in Canada.
Symptoms
Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, patients typically present with polyuriaPolyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
(production of large volume of urine), polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
(excessive liquid intake), and mild proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(the abnormal appearance of protein in the urine), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
or a kidney transplant in order to survive.
Approximately 10% of individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include blindness, liver problems, severe global developmental delay or mental retardation, and neurologic involvement in which the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
is affected.
Histology
Histologically, nephronophthisis is characterized by fibrosis and the formation of cysts in a specific region of the kidney. In contrast to other cystic diseases of the kidney in which the kidneys are larger than usual, in nephronophthisis the kidneys are small to normal in size.Pathophysiology
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of individuals and families with nephronophthisis, scientists have identified thus far 8 different genes in which mutations can cause the disease. These genes are called NPHP1
NPHP1
Nephrocystin-1 is a protein that in humans is encoded by the NPHP1 gene.-Interactions:NPHP1 has been shown to interact with BCAR1, PTK2B, Filamin and INVS.-Further reading:...
, NPHP2, NPHP3
NPHP3
Nephrocystin-3 is a protein that in humans is encoded by the NPHP3 gene.-Further reading:...
, NPHP4
NPHP4
Nephrocystin-4 is a protein that in humans is encoded by the NPHP4 gene.-Further reading:...
, NPHP5, NPHP6, NPHP7, and NPHP8, and the proteins for which they encode are known as the nephrocystins. Although the biological function of these proteins is not yet known, they all localize at least in part to an organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
in the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
called the primary cilia.
Relation to other rare genetic disorders
Recent findings in genetic research have suggested that a large number of genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s, both genetic syndromes
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
and genetic diseases
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
root cause of the widely-varying, phenotypically
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
-observed disorders. Thus, Nephronophthisis is a ciliopathy
Ciliopathy
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosomes, it is possible for ciliopathies to be associated...
. Other known ciliopathies include primary ciliary dyskinesia
Primary ciliary dyskinesia
Primary ciliary dyskinesia , also known as immotile ciliary syndrome or Kartagener Syndrome ', is a rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract and fallopian tube, and also of the flagella of sperm in...
, Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
, polycystic kidney
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
and liver disease
Polycystic liver disease
Polycystic liver disease usually describes the presence of multiple cysts scattered throughout normal liver tissue, in association with polycystic kidney disease.-Pathophysiology:Associations with PRKCSH and SEC63 have been described....
, Alstrom syndrome
Alstrom syndrome
Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in...
, Meckel-Gruber syndrome and some forms of retinal degeneration
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
.