nephronophthisis 4

Nephronophthisis 4 (NPHP4) Description

Nephronophthisis 4, also known as juvenile nephronophthisis, is a rare genetic disorder that affects the kidneys. It is characterized by:

• Reduced renal concentrating ability
• Chronic tubulointerstitial nephritis
• Cystic renal disease
• Progression to end-stage renal disease (ESRD) before age 30 years [1]

This condition is caused by homozygous or compound heterozygous mutation in the NPHP4 gene on chromosome 1p36. The same genetic mutation also causes Senior-Loken syndrome, a combination of nephronophthisis with retinitis pigmentosa (SLSN4; 606996) [3].

The symptoms of nephronophthisis 4 include:

• Polyuria
• Growth retardation
• Deterioration of renal function during childhood or adolescence [5]
• Anemia and growth retardation [6][9]

It is a progressive tubulo-interstitial kidney disorder that inevitably leads to end-stage kidney disease [7]. Nephronophthisis 4 is an autosomal recessive condition, meaning it is inherited in an autosomal recessive fashion.

References:

[1] - The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized ...

[3] - A number sign (#) is used with this entry because of evidence that nephronophthisis-4 (NPHP4) is caused by homozygous or compound heterozygous mutation in the NPHP4 gene on chromosome 1p36. The same genetic mutation also causes Senior-Loken syndrome, a combination of nephronophthisis with retinitis pigmentosa (SLSN4; 606996)

[5] - Deterioration of renal function during childhood or adolescence

[6] - Anemia and growth retardation

[7] - It is a progressive tubulo-interstitial kidney disorder that inevitably leads to end-stage kidney disease

[9] - Anemia and growth retardation

Early Signs and Symptoms

Nephronophthisis 4 (NPHP4) often presents with non-specific symptoms that may be easily overlooked. Early signs include:

• Increased thirst ([10])
• Excessive urination (polyuria) ([5], [10])
• General fatigue ([6], [10])

These symptoms result from the kidney's impaired ability to concentrate urine, leading to fluid and electrolyte imbalances.

Additional Symptoms

As NPHP4 progresses, additional symptoms may appear, including:

• Kidney scarring and inflammation ([11])
• Anemia ([7], [9])
• High blood pressure ([7], [9])
• Skeletal abnormalities ([9])

In rare cases, NPHP4 may also involve extra-renal systems, such as the liver, heart, or other organs.

Age of Onset

Symptoms of NPHP4 may start to appear at various ages, ranging from childhood to young adulthood. The age of onset can vary depending on the specific disease and individual factors ([12]).

It's essential to note that these symptoms can be similar to those of other kidney diseases, making diagnosis challenging. A comprehensive medical evaluation, including genetic testing, is necessary to confirm NPHP4.

References:

[5] - Symptoms include polyuria, polydipsia with regular fluid intake, impaired sodium reabsorption that cause hypovolemia and hyponatremia. [6] - General symptoms of renal failure may be present such as fatigue, pruritus, nausea, vomiting, uremic gastritis, anemia and growth retardation. [7] - Bed-wetting is often seen in school-aged children due to increased urine production. Anaemia and high blood pressure are also common. [9] - The disease is characterized by severe hypertension, anemia, skeletal abnormalities and increased thirst and urination. [10] - Early signs include increased thirst , excessive urination (polyuria), and general fatigue. [11] - Kidney scarring and inflammation are both symptoms that can indicate an individual is affected by nephronophthisis. The DNA mutations that occur in affected individuals cause the primary cilia inside of the kidneys to have defects. [12] - Symptoms may begin in a single age range, or during several age ranges. The symptoms of some diseases may begin at any age.

Nephronophthisis type 4 (NPHP4) is a genetic disorder that affects the kidneys. Diagnostic testing for NPHP4 can be crucial in identifying the condition and informing prognosis and clinical management.

According to available information, diagnostic testing for NPHP4 typically involves genetic testing [number 3]. This type of testing can help identify mutations in the NPHP4 gene, which is associated with the disorder. Genetic testing can also inform prognosis and clinical management by providing insights into the potential severity and progression of the condition.

In addition to genetic testing, other diagnostic tests may be used to support a diagnosis of NPHP4. These may include renal biopsy [number 4], which involves taking a sample of kidney tissue for examination under a microscope. Renal biopsy can help confirm the presence of characteristic histological features associated with NPHP4.

Other diagnostic tests that may be used in conjunction with genetic testing and renal biopsy include:

• Blood tests to examine kidney function and detect potential electrolyte imbalances or metabolic disorders [number 7]
• Urine tests to assess kidney function and detect potential abnormalities [number 6]

It's worth noting that a definitive diagnosis of NPHP4 can only be made through renal biopsy or mutation analysis [number 4]. Mutation analysis should be initiated in patients with a clinical suspicion of NPHP4, as it can inform prognosis and clinical management.

References:

• [number 3]
• [number 4]

Based on the provided context, it appears that there are currently no specific drug treatments available for Nephronophthisis type 4.

• According to search result [10], a vasopressin V2 receptor antagonist is being considered as a possible future treatment, but it does not mention any current or existing drug treatment.
• Search result [9] mentions that in early disease, treatment involves management of hypertension, electrolyte abnormalities and acid-base disorders, and anemia, but it does not specify any specific drug treatment for Nephronophthisis type 4.
• Search results [7], [8], and [11] all mention that there is currently no therapeutic alternative other than dialysis and kidney transplantation for NPH-RC forms leading to ESKD, which suggests that there are no effective drug treatments available.

Therefore, it can be concluded that:

• There is currently no specific or targeted drug treatment available for Nephronophthisis type 4.
• Management of symptoms such as hypertension, electrolyte abnormalities and acid-base disorders, and anemia may be part of the treatment plan in early disease.
• Dialysis and kidney transplantation are necessary for ESRD management.

Citations:

[10] mentions a possible future treatment but does not specify any current drug treatment. [9] discusses general treatment options but does not mention specific drugs for Nephronophthisis type 4. [7], [8], and [11] all suggest that there are no effective drug treatments available.

Differential Diagnosis of Nephronophthisis Type 4

Nephronophthisis type 4 (NPHP4) is a rare and autosomal recessive form of cystic kidney disease. The differential diagnosis for NPHP4 includes several conditions that can mimic its clinical presentation.

• Autosomal Recessive Polycystic Kidney Disease (ARPKD): This condition is characterized by the development of cysts in both kidneys, leading to progressive renal dysfunction. ARPKD can present with similar symptoms to NPHP4, including kidney enlargement and impaired kidney function.
• Early-Onset Autosomal Dominant Polycystic Kidney Disease (ADPKD): Although ADPKD is typically inherited in an autosomal dominant pattern, some cases have been reported to occur at a younger age. These early-onset cases can be mistaken for NPHP4 due to their similar clinical presentation.
• Renal Hypodysplasia: This condition involves the underdevelopment of kidney tissue, leading to impaired kidney function and cyst formation. Renal hypodysplasia can present with symptoms similar to NPHP4, including kidney enlargement and impaired kidney function.

Key Points

• The differential diagnosis for NPHP4 includes ARPKD, early-onset ADPKD, and renal hypodysplasia.
• These conditions can mimic the clinical presentation of NPHP4 due to their similar symptoms.
• Accurate diagnosis requires genetic testing and imaging studies to rule out these differential diagnoses.

References

[3] by F Luo · 2018 · Cited by 110 — Early onset autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease are often in the main differential ... [4] Differential diagnosis includes autosomal recessive polycystic kidney disease, early-onset autosomal dominant polycystic kidney disease, and renal ... [10] If no mutations are found additional NPHP genes should be screened depending on phenotype and a differential diagnosis of MCKD, ARPKD and BBS should be considered.