nephronophthisis 16

Nephronophthisis 16, also known as NPHP16, is a rare genetic disorder that affects the kidneys and can lead to end-stage renal failure.

Characteristics of NPHP16:

• Chronic kidney disease: NPHP16 is characterized by chronic kidney disease that can progress to end-stage renal failure.
• Cystic kidneys: Patients with NPHP16 may present with cystic kidneys of normal size or slightly enlarged kidneys.
• Genetic cause: The disease is caused by a homozygous mutation in the ANKS6 gene on chromosome 9q22.

Other symptoms:

• Severe hypertension
• Anemia
• Skeletal abnormalities
• Increased thirst and urination

Heritability: NPHP16 is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated ANKS6 gene (one from each parent) to develop the disease.

References:

• [1] Any nephronophthisis in which the cause of the disease is a mutation in the ANKS6 gene. Synonyms. ANKS6 nephronophthisis (disease); NPHP16; autosomal recessive ...
• [4] A number sign (#) is used with this entry because nephronophthisis-16 (NPHP16) is caused by homozygous mutation in the ANKS6 gene (615370) on chromosome 9q22. ...
• [6] nephronophthisis 16. Description. Any nephronophthisis in which the cause of the disease is a mutation in the ANKS6 gene. Heritability. Causal Genes. ANKS6.
• [8] NPHP16 Alt IDs: OMIM:615382. Definition: A nephronophthisis that has_material_basis_in homozygous mutation in the ANKS6 gene on chromosome 9q22. Term Browser ...

Early Signs and Symptoms of Nephronophthisis

Nephronophthisis often presents insidiously, with non-specific symptoms that may be easily overlooked. Early signs include:

• Increased thirst (polydipsia)
• Excessive urination (polyuria)
• General fatigue
• These symptoms result from the kidney's impaired ability to concentrate urine, leading to fluid and electrolyte imbalances.

As the disease progresses, more severe symptoms may develop, including:

• Severe hypertension
• Anemia
• Skeletal abnormalities
• Increased thirst and urination

In some cases, nephronophthisis may also involve extra-renal systems, such as liver fibrosis or heart abnormalities. The age of onset for these symptoms can vary widely, from infancy to adulthood.

References:

• [10] Early Signs. Nephronophthisis often presents insidiously, with non-specific symptoms that may be easily overlooked.
• [12] Nephronophthisis is a disorder that affects the kidneys. It is characterized by inflammation and scarring (fibrosis) that impairs kidney function.
• [14] Diagnosing nephronophthisis. Symptoms and signs in NPHP manifest slowly and are subtle.
• [10] Early Signs. Nephronophthisis often presents insidiously, with non-specific symptoms that may be easily overlooked.

Diagnostic Tests for Nephronophthisis

Nephronophthisis (NPHP) can be diagnosed through various diagnostic tests, which are crucial in confirming the presence of this genetic disorder.

• Genetic Testing: Genetic testing plays a pivotal role in diagnosing nephronophthisis. Identifying mutations in the relevant genes confirms the diagnosis and allows for genetic counseling and family planning [11]. Thorough genetic screening is crucial in individuals with a family history of kidney disease or those presenting symptoms suggestive of NPHP.
• Renal Biopsy: The diagnosis can also be made by renal biopsy, which involves examining tissue samples from the kidneys to identify characteristic findings associated with NPHP [12].
• Imaging Tests: Computed tomography (CT) and ultrasonography are imaging tests usually used to detect cysts in the kidneys, a hallmark of NPHP [13]. These tests can help confirm the diagnosis.
• Laboratory Tests: Laboratory tests may indicate poor kidney function, dilute urine, and possibly a low level of sodium or potassium and high level of uric acid in the blood [13].
• Family History: A family history of this type of kidney disease is an important clue to the diagnosis [13].

These diagnostic tests are essential in confirming the presence of nephronophthisis and guiding further management.

Current State of Drug Treatment for Nephronophthisis

Nephronophthisis (NPH) is a rare genetic disorder that affects the kidneys and has no specific curative treatment available. The current drug therapy for NPH is primarily supportive, aimed at managing symptoms related to chronic kidney disease.

• Supportive Care: The management of NPH involves maintaining fluid and metabolic balance, including correction of water and electrolyte imbalances [5].
• Untargeted Therapies: Research has explored various untargeted therapies in NPH model systems, but these have not been proven effective in treating the disease [2].

Emerging Promising Therapies

Recent studies suggest that promising therapeutic approaches may be on the horizon for NPH. These include:

• Ciliopathy-Associated Gene Therapy: Research has shown potential in using gene therapy to target ciliopathy-associated genes, which could lead to a more effective treatment for NPH [7][10].
• Gene Editing Techniques: Gene editing techniques, such as CRISPR/Cas9, may also be used to correct genetic mutations associated with NPH [7].
• Targeted Drug Therapies: Targeted drug therapies are being explored as potential treatments for NPH, including agonists of prostaglandin E2 receptors [4].

Current Research Efforts

Researchers at Newcastle University are actively working on finding a treatment for NPH. They plan to test a panel of candidate drugs to identify potential therapeutic options [8].

The differential diagnosis of nephronophthisis (NPH) involves considering various conditions that can mimic its clinical presentation. Here are some key points to consider:

• Autosomal Recessive Polycystic Kidney Disease (ARPKD): This is a genetic disorder characterized by the development of cysts in both kidneys, leading to kidney enlargement and dysfunction. ARPKD can present with similar symptoms to NPH, including chronic kidney disease and end-stage renal failure [1].
• Early-Onset Autosomal Dominant Polycystic Kidney Disease (ADPKD): This is a genetic disorder that causes the growth of numerous cysts in both kidneys, leading to kidney enlargement and dysfunction. Early-onset ADPKD can present with similar symptoms to NPH, including chronic kidney disease and end-stage renal failure [2].
• Renal Hypodysplasia: This is a rare congenital disorder characterized by underdevelopment of the kidneys, leading to chronic kidney disease and end-stage renal failure. Renal hypodysplasia can present with similar symptoms to NPH, including chronic kidney disease and end-stage renal failure [3].
• Autosomal Recessive Cystic Kidney Diseases: These are a group of genetic disorders characterized by the development of cysts in both kidneys, leading to kidney enlargement and dysfunction. Autosomal recessive cystic kidney diseases can present with similar symptoms to NPH, including chronic kidney disease and end-stage renal failure [4].
• Bardet-Biedl Syndrome (BBS): This is a rare genetic disorder characterized by the development of cysts in both kidneys, leading to kidney enlargement and dysfunction. BBS can present with similar symptoms to NPH, including chronic kidney disease and end-stage renal failure [5].

It's essential to consider these differential diagnoses when evaluating patients with suspected nephronophthisis, as accurate diagnosis is crucial for guiding treatment and management decisions.

References:

[1] 5 [2] 10 [3] 14 [4] 12 [5] 13