CPSI Disease

#CPSI_disease

It appears you are referring to CPS I deficiency — a serious but very rare metabolic condition affecting the urea cycle, specifically the mitochondrial enzyme carbamoyl phosphate synthetase I (CPS1). Here’s a structured overview:

1. What Is CPS I Deficiency?

• Carbamoyl phosphate synthetase I deficiency (CPS I deficiency) is an autosomal recessive genetic disorder.

• It impairs the first and rate-limiting step of the urea cycle, which converts toxic ammonia into urea for excretion .

• Without functional CPS1, ammonia accumulates in the blood (known as hyperammonemia), causing acute and chronic neurological damage .

2. Causes and Genetics

• Caused by mutations in the CPS1 gene, leading to either a complete or partial absence of active enzyme .

• Patients must inherit two mutated copies (one from each parent)—as carriers are typically asymptomatic .

• Genetic studies show many mutations lead to RNA instability via nonsense-mediated decay (e.g., splicing defects, frameshifts) .

3. Clinical Presentation

Neonatal-Onset Forms (Severe)

• Symptoms emerge within days of birth:

• Lethargy, poor feeding, temperature instability

• Respiratory irregularities, vomiting, seizures, possible coma

• Often leads to rapid clinical deterioration and irreversible brain injury if untreated  .

Late-Onset or Partial Forms (Milder)

• May appear later in childhood or adulthood under metabolic stress (e.g., infection, high protein intake).

• Features include episodic vomiting, confusion, ataxia, and variable neurological impairment.

4. Diagnosis

• Newborn screening may detect low citrulline levels as a biochemical clue .

• Diagnostic tests include:

• Measurement of plasma ammonia, amino acids (elevated glutamine, alanine; low citrulline, arginine)

• Urine orotic acid (typically normal in CPS I deficiency)

• Genetic testing for CPS1 variants  .

5. Treatment & Management

• Emergency management: Rapid reduction of ammonia using:

• Protein restriction, IV glucose/lipids to prevent catabolism

• Nitrogen-scavenging medications (e.g., sodium benzoate, phenylacetate, phenylbutyrate)

• Arginine supplementation

• Hemodialysis in severe hyperammonemic crises  .

• Long-term care: Metabolic specialist oversight with:

• Diet control, medications, monitoring for ammonia levels

• Preventing metabolic decompensation during illness or stress.

• Recent breakthrough: A 2025 NEJM study reported a targeted base-editing therapy using lipid nanoparticles in an infant. The treatment improved protein tolerance and reduced nitrogen scavenger needs without major side effects. Long-term effects are still under study   .

6. Prognosis & Implications

• The neonatal-onset form has a high mortality risk and often severe neurodevelopmental impairment.

• Partial forms may have better outcomes with early diagnosis and strict management.

• Early detection, such as newborn screening and prompt intervention, critically improve outcomes.

Summary Table

항목 내용

질환명 CPS I deficiency (CPSID)

원인

CPS1 유전자 돌연변이, autosomal recessive 유전

병리 기전

요소 회로 첫 단계 효소 결핍 혈중 암모니아 축적

증상 및 발현 시기

신생아기(심각한 경우) / 후기(스트레스 유발 시)

진단 방법

신생아 screening, 혈암모니아, 아미노산 패널, 유전자 검사

치료 전략

단백질 제한,질소 제거제,응급 분쇄,유전자 편집 연구 중

예후

조기 발견 시 관리 가능, 신경 손상 가능성 있음

궁금하신 점이 있으면 예를 들어:

다른 요소 회로 이상과 차이점 (예: OTC deficiency 등)

유전자 변이 별 임상 양상 연관

base-editing 유전자 치료의 세부 내용 및 적용 가능성