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Updated: Dec 25 2021

CPS deficiency

  • Snapshot
    • A 5-day-old boy is brought to the hospital by his parents due to recurrent seizures and increased work of breathing for the past day. The patient was born via vaginal delivery to a G1P0 mother, who had an uncomplicated labor and uneventful prenatal history. The parents note that the baby has had 4 seizures, involving spasms of the upper and lower limbs, throughout the course of the day. The patient's temperature is 100.1°F (37.8°C), pulse is 190/min, and respirations are 68/min. Lab studies reveal a blood ammonia of 1020 mg/dL.
  • Introduction
    • Overview
      • carbamyl phosphate synthetase (CPS) deficiency is a urea cycle defect
        • leads to elevated blood ammonia levels
  • ETIOLOGY
    • Pathophysiology
      • CPS is a hepatocellular enzyme, present in hepatic mitochondria
        • deficiency of CPS impairs the hepatic urea cycle, the major pathway for waste nitrogen disposal
    • Genetics
      • autosomal recessive
  • Epidemiology
    • Incidence
      • rare
    • Demographics
      • has been reported in patients of all ages, from newborns to adults
        • serious disease in newborns with rapid decline
  • Presentation
    • Symptoms
      • anorexia
      • irritability
      • heavy or rapid breathing
      • lethargy
      • vomiting
      • seizures
      • coma
    • Physical exam
      • tachypnea
      • hepatomegaly
      • poor coordination
      • hypotonia or hypertonia
      • ataxia
      • tremor
  • Studies
    • Blood ammonia level
      • sole laboratory criterion for diagnosis
        • ammonia levels usually are 10-20 times higher than reference range
          • values > 1000mg/dL are common
  • Differential
    • Arginosuccinate (ASA) lyase deficiency
      • key distinguishing factor
        • ↑ levels of ASA in the blood and urine
    • Ornithin transcarbamylase (OTC) deficiency
      • key distinguishing factor
        • ↑ levels of urinary orotic acid
        • age of onset is usually after childhood
  • Treatment
    • Lifestyle
      • ↓ protein intake
    • Medical
      • hemodialysis
        • indications
          • patients with an extremely high blood ammonia level
  • Prognosis
    • Severe CNS impairment is likely in patients with neonatal onset
    • Untreated CPS deficiency is likely fatal
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