nephronophthisis 2

Nephronophthisis-2 (NPHP2) Description

Nephronophthisis-2, also known as NPHPL2, is an autosomal recessive cystic kidney disease characterized by the onset of progressive renal insufficiency in children. This disorder leads to chronic tubulointerstitial nephropathy and inevitably results in end-stage kidney disease.

Key Features:

• Autosomal recessive inheritance pattern
• Progressive renal insufficiency in children
• Chronic tubulointerstitial nephropathy
• Cysts often develop in the kidneys
• Inevitable progression to end-stage kidney disease

Causes and Genetics: Nephronophthisis-2 is caused by homozygous or compound heterozygous mutation in the inversin gene, which plays a crucial role in maintaining proper ciliary function. This genetic defect leads to impaired kidney function and eventual renal failure.

References:

• [4] A number sign (#) is used with this entry because nephronophthisis-2 (NPHP2) is caused by homozygous or compound heterozygous mutation in the inversin gene ...
• [8] Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy in which cysts often develop. It inevitably leads to end-stage kidney disease.
• [9] A rare, genetic, renal ciliopathy characterized by reduced ability of the kidneys to concentrate solutes, chronic tubulointerstitial nephritis.

Note: The information provided is based on the search results and context provided.

Signs and Symptoms of Nephronophthisis

Nephronophthisis (NPHP) is a genetic disorder that affects the kidneys, leading to end-stage renal disease. The signs and symptoms of NPHP can vary from one individual to another and may be mild or severe, depending on the form of the condition.

Common Signs and Symptoms:

• Kidney-related symptoms: Polyuria (excessive urine production), polydipsia (excessive thirst), weakness, and fatigue are common signs and symptoms of NPHP. [1][4]
• Anemia and growth retardation: Anemia and growth retardation can also occur in individuals with NPHP. [14]
• Hypertension: While hypertension is not typically present in juvenile nephronophthisis, it may be a feature in other forms of the condition. [15]

Other Organ System Involvement:

When other organ systems are affected, symptoms can include:

• Situs inversus: A rare congenital anomaly where the organs are reversed or mirrored on the opposite side.
• Heart abnormalities: Abnormalities such as atrial septal defects and ventricular septal defects may occur in individuals with NPHP. [15]
• Liver fibrosis: Liver fibrosis, a condition characterized by scarring of the liver tissue, can also be associated with NPHP.

Age-Related Symptoms:

The age at which symptoms appear can vary depending on the form of NPHP:

• Infantile nephronophthisis: Symptoms may be present before birth or shortly after birth.
• Juvenile nephronophthisis: Symptoms typically become apparent in childhood, with polyuria and polydipsia being common features. [15]
• Adolescent nephronophthisis: Symptoms may develop later in life, often during adolescence.

It's essential to note that the progression of NPHP can vary significantly among individuals, and some people may experience more severe symptoms than others. If you suspect someone has NPHP, it is crucial to consult a healthcare professional for proper diagnosis and treatment.

Based on the provided context, here are the diagnostic tests for Nephronophthisis (NPHP) 2:

• Genetic testing: A positive genetic test confirms the diagnosis of NPHP (see [4], [9]). The Invitae Nephronophthisis Panel analyzes 27 genes associated with NPHP, including INVS encoding inversin, which causes NPHP type 2 ([10]).
• Renal biopsy: While the role of renal biopsy in diagnosis is controversial, it may be used to distinguish NPHP from other differential diagnoses ([8], [14]). However, molecular genetic analysis is currently the only definitive diagnostic method.
• Clinical evaluation: Establishing care with an engaged and dedicated primary care provider (PCP) can improve care and shorten the time to reach an accurate diagnosis ([12]).
• Imaging studies: Prenatal imaging may reveal cystic kidney disease and other abnormalities in at-risk pregnancies ([10]).

It's worth noting that a 20-gene panel, including assessment of non-coding variants, is ideal for patients with a clinical suspicion of nephronophthisis ([5]). Additionally, next-generation sequencing has revolutionized the molecular diagnosis of individuals affected by genetic kidney diseases ([4]).

Based on the provided context, it appears that there is no specific drug treatment available for Nephronophthisis Type 2 (NPH2). However, research suggests that a vasopressin V2 receptor antagonist may be a potential future treatment option.

According to search result [10], possible future treatment might include a vasopressin V2 receptor antagonist, because in the pcy mouse, this treatment has shown promise. Additionally, search result [12] mentions that potential treatments, targeted towards the collecting duct, may be available for future use.

It's essential to note that these are potential future treatment options and not currently available as a standard treatment for NPH2. The management of NPH2 is primarily supportive, focusing on maintaining fluid and metabolic balance, correcting water and electrolyte imbalances, and managing anemia [3][9].

Therefore, the current drug treatment options for Nephronophthisis Type 2 are limited to supportive care, with no specific targeted therapy available. However, ongoing research may lead to the development of new treatments in the future.

References:

• Search result [10]: Possible future treatment might include a vasopressin V2 receptor antagonist.
• Search result [12]: Potential treatments, targeted towards the collecting duct, may be available for future use.
• Search result [3]: Anemia treatment as the individual's condition warrants.
• Search result [9]: Treatment involves management of hypertension, electrolyte abnormalities and acid-base disorders, and anemia.

Differential Diagnosis of Nephronophthisis Type 2

Nephronophthisis type 2 (NPHP2) is a rare genetic disorder that affects the kidneys and other organs. The differential diagnosis of NPHP2 involves identifying conditions that may present with similar symptoms.

Conditions to Consider:

• Autosomal Recessive Polycystic Kidney Disease (ARPKD): This condition also presents with cysts in the kidneys, but it is more common than NPHP2.
• Congenital Anomalies of the Kidneys and Urinary Tract: These anomalies can cause similar symptoms to NPHP2, such as kidney dysfunction and cyst formation.
• Bardet-Biedl Syndrome (BBS): This rare genetic disorder affects multiple organs, including the kidneys, and may present with similar symptoms to NPHP2.

Key Features to Consider:

• Genetic Testing: Genetic testing is essential for diagnosing NPHP2. A positive test can confirm the diagnosis.
• Clinical Presentation: The clinical presentation of NPHP2 includes kidney dysfunction, cyst formation, and other systemic symptoms.
• Imaging Studies: Imaging studies such as ultrasound or CT scans may show cysts in the kidneys.

References:

• [3] Homozygous NPHP1 deletions are reported as the cause of kidney failure in 0.5% of adults.
• [13] 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.
• [14] DIFFERENTIAL DIAGNOSIS — The presence of the associated extra-renal findings (eg, ... Otto EA, Schermer B, Obara T, et al. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.