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Infantile Nephronophthisis

Disease Details

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Description: Infantile nephronophthisis is a genetic disorder characterized by the progressive loss of kidney function, leading to end-stage renal disease typically before the age of five.
Type: Infantile nephronophthisis is a type of genetic kidney disorder. It is transmitted in an autosomal recessive manner.
Signs And Symptoms: Infantile nephronophthisis is a genetic disorder that affects the kidneys and can lead to renal failure. Signs and symptoms typically become apparent in infancy and may include:

- Excessive thirst (polydipsia)
- Increased urination (polyuria)
- Dehydration
- Growth retardation
- Anemia
- Developmental delay
- Hypertension (in some cases)
- Kidney abnormalities detected via ultrasound

Early diagnosis and management are crucial to address complications and improve quality of life.
Prognosis: Infantile nephronophthisis is a genetic disorder that primarily affects the kidneys and can lead to end-stage renal disease (ESRD) typically within the first decade of life. The prognosis varies depending on the severity and management of the condition. Early diagnosis and supportive treatments, including dialysis or kidney transplantation, can improve the quality of life and long-term outlook for affected individuals. However, the disease often progresses to ESRD despite these interventions.
Onset: Infantile nephronophthisis typically has an onset in the first year of life. It is a rare genetic disorder that affects the kidneys, leading to progressive renal failure.
Prevalence: The prevalence of infantile nephronophthisis is not well-defined due to its rarity, but it is estimated to affect approximately 1 in 50,000 to 1 in 100,000 individuals.
Epidemiology: Infantile nephronophthisis is a rare genetic disorder characterized by the progressive loss of kidney function. Its incidence is estimated at 1 in 50,000 live births. The disease typically presents in early childhood and is inherited in an autosomal recessive pattern, meaning both copies of a gene in each cell have mutations. Early detection and intervention are crucial for managing the condition and delaying end-stage renal disease.
Intractability: Yes, infantile nephronophthisis is considered intractable. It is a genetic disorder characterized by the progressive loss of kidney function, ultimately leading to end-stage renal disease (ESRD). There is currently no cure, and the management focuses on supportive care and, eventually, kidney transplantation.
Disease Severity: Infantile nephronophthisis is a severe hereditary kidney disorder. It typically progresses to end-stage renal disease, usually within the first few years of life. Kidney function deteriorates rapidly, leading to a need for dialysis or kidney transplantation.
Pathophysiology: Infantile nephronophthisis is a genetic disorder that affects kidney function. In terms of pathophysiology, the disease is characterized by the progressive loss of kidney tissue, leading to fibrosis and cyst formation at the corticomedullary junction. This process ultimately impairs the kidneys' ability to concentrate urine and leads to renal insufficiency and eventually chronic kidney disease. NPHP genes, particularly NPHP2 (INVS), are commonly implicated in this condition. These genes are involved in the function of primary cilia, cellular structures critical for signaling pathways that maintain normal kidney development and function. Dysfunction in these cilia leads to the pathological changes seen in nephronophthisis.
Carrier Status: Infantile nephronophthisis is an autosomal recessive disorder. Carrier status for this condition means that an individual has one copy of the mutated gene and typically does not show symptoms of the disease but can pass the mutation to offspring. If both parents are carriers, each child has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected.
Mechanism: Infantile nephronophthisis (NPHP) is a kidney disorder characterized by the progressive loss of kidney function, typically leading to end-stage renal disease. The primary mechanism involves cyst development and fibrosis in the kidneys.

**Molecular Mechanisms:**

1. **Genetic Mutations:** NPHP is frequently associated with mutations in genes encoding proteins that are parts of the primary cilia or basal bodies. These genes include NPHP1, NPHP2, NPHP3, and others. Mutations in these genes disrupt normal renal tubular function.

2. **Ciliopathy:** The affected proteins are involved in the structure and function of primary cilia, which are essential for various signaling pathways in cells. Primary cilia act as sensory organelles, and their dysfunction leads to abnormal signal transduction, resulting in cyst formation and fibrosis in kidney tissues.

3. **Cell Signaling Pathways:** Disruption in ciliary function affects multiple signaling pathways, notably the Hedgehog, Wnt, and mTOR pathways, leading to abnormalities in cell proliferation and differentiation that contribute to the pathogenesis of NPHP.

Overall, the combination of genetic mutations and resultant ciliopathy underlies the molecular mechanisms leading to infantile nephronophthisis.
Treatment: There is no cure for infantile nephronophthisis. Treatment primarily focuses on managing symptoms and slowing disease progression. This can include:

1. **Medications:** To control symptoms such as high blood pressure.
2. **Diet and Supplements:** Managing electrolyte imbalances and ensuring proper nutrition.
3. **Dialysis:** For kidney failure management.
4. **Kidney Transplant:** The definitive treatment once the kidneys fail completely.

Close monitoring by nephrologists and supportive care is crucial.
Compassionate Use Treatment: Infantile nephronophthisis is a genetic disorder affecting the kidneys, leading to progressive kidney failure. Treatment primarily focuses on managing symptoms and slowing disease progression. Here are current approaches regarding compassionate use and experimental treatments:

1. **Compassionate Use Treatment**:
- **Renal Transplantation**: Often considered when the disease progresses to end-stage renal disease (ESRD). Although not curative, a kidney transplant can significantly improve quality of life.
- **Supportive Care**: Includes management of electrolyte imbalances, anemia, and blood pressure control.

2. **Off-Label or Experimental Treatments**:
- **ACE Inhibitors/ARBs**: These medications may be used off-label to help control blood pressure and reduce proteinuria, potentially slowing the progression of kidney damage.
- **mTOR Inhibitors**: Investigational use of drugs like sirolimus and everolimus is being explored for their potential to slow disease progression by affecting cellular pathways involved in cyst formation.
- **Gene Therapy**: Experimental approaches focusing on correcting the underlying genetic defects causing the disease. These are still in early stages of research.
- **Stem Cell Therapy**: Another experimental treatment being researched, focusing on regenerating damaged kidney tissues.

Patients considering these treatments should consult with their healthcare team to discuss options, potential benefits, and associated risks.
Lifestyle Recommendations: For infantile nephronophthisis:

**Lifestyle Recommendations:**
1. **Regular Monitoring**: Frequent medical check-ups to monitor kidney function and overall health.
2. **Proper Hydration**: Encouraging adequate fluid intake to support kidney health, under the guidance of a healthcare provider.
3. **Balanced Diet**: Nutrient-rich diet with appropriate levels of protein, sodium, and potassium, customized by a dietitian.
4. **Physical Activity**: Age-appropriate physical activities that improve overall health while considering the child's energy levels.
5. **Medication Adherence**: Strict adherence to prescribed medications and treatment regimens.
6. **Infection Prevention**: Focus on hygiene and avoidance of infections to prevent additional kidney stress.
7. **Emotional Support**: Psychological support for the child and family to cope with chronic illness.

Specific plans should always be tailored with the guidance of a healthcare professional.
Medication: There is no specific medication to cure infantile nephronophthisis. Treatment primarily focuses on managing symptoms and complications, such as maintaining electrolyte balance, controlling high blood pressure, and supporting kidney function. Ultimately, many patients may require dialysis or a kidney transplant due to progressive kidney failure.
Repurposable Drugs: Repurposable drugs for infantile nephronophthisis are not well-established. This condition is a rare genetic disorder that primarily affects kidney function, leading to cyst formation and fibrosis. Due to its rarity and genetic basis, conventional treatments have limited efficacy, and specific repurposable drugs are not commonly identified. Current management primarily focuses on supportive care, including managing symptoms and addressing kidney failure through interventions such as dialysis or kidney transplantation. Research is ongoing, and emerging therapies may offer potential in the future.
Metabolites: Infantile nephronophthisis is a genetic disorder affecting kidney function. Characteristic metabolites include increased serum creatinine and urea due to impaired kidney filtration. Electrolyte imbalances, such as elevated potassium and phosphorus or reduced bicarbonate, are also common.
Nutraceuticals: Currently, there is no established evidence or research supporting the use of nutraceuticals for treating infantile nephronophthisis. This genetic disorder primarily affects the kidneys, leading to progressive kidney failure. Standard management focuses on supportive care, including managing symptoms and preparing for potential kidney transplantation, since there is no cure for the condition. Discussing any alternative treatments or supplements with a healthcare provider is essential to ensure safety and efficacy.
Peptides: In infantile nephronophthisis, peptides, especially those involved in fibrosis and inflammation, can play a role in disease progression. However, the primary issue in this genetic disorder is the malfunction and eventual failure of the kidneys due to structural abnormalities. Research into peptide-based therapies is ongoing, but they are not yet a standard treatment.