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Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan
Insights
Urea cycle disorders (UCDs) are common inborn errors of metabolism. Early diagnosis and aggressive treatment, especially controlling blood ammonia levels, are crucial for improving outcomes and reducing neurodevelopmental deficits in patients with UCDs.
Area of Science:
- Metabolic Disorders
- Genetics
- Pediatrics
Background:
- Urea cycle disorders (UCDs) represent a significant group of inborn errors of metabolism in Japan, with a prevalence of approximately 1 in 50,000 live births.
- Ornithine transcarbamylase (OTC) deficiency is the most prevalent UCD, accounting for two-thirds of all cases.
Purpose of the Study:
- To investigate the clinical manifestations and prognosis of UCDs in a large cohort of Japanese patients.
- To identify factors influencing neurodevelopmental outcomes and survival rates in both neonatal-onset and late-onset UCD cases.
Main Methods:
- Retrospective analysis of 216 patients diagnosed and treated for UCDs between 1978 and 1995.
- Categorization of patients into neonatal-onset (92 cases) and late-onset (116 cases) groups.
- Correlation of peak blood ammonia levels during the first hyperammonaemic attack with neurodevelopmental outcomes in 108 cases.
Main Results:
- The 5-year survival rates were 22% for neonatal-onset UCD and 41% for late-onset UCD.
- Among survivors, 90% of neonatal-onset UCD patients exhibited moderate to severe neurodevelopmental deficits, compared to 28% of late-onset UCD survivors.
- Peak blood ammonia levels exceeding 350 mumol/L during the initial hyperammonaemic attack were associated with mortality or severe neurological deficits, while levels below 180 mumol/L were linked to no severe neurological damage.
Conclusions:
- Early diagnosis and aggressive management, particularly controlling hyperammonaemia, are critical for improving the prognosis of UCDs.
- Blood ammonia levels serve as a key indicator for predicting neurodevelopmental outcomes in UCD patients.
- Timely intervention can significantly mitigate the severity of neurological sequelae in individuals with urea cycle disorders.
Abstract:
In Japan, urea cycle disorders (UCDs) are one of the most frequent inborn errors of metabolism, estimated to have a prevalence of 1 per 50,000 live births. In an attempt to develop more effective treatment and enhance the quality of life, we investigated the clinical manifestations and prognosis of 216 patients with UCDs diagnosed and treated between 1978 and 1995. These included 92 cases of neonatal-onset UCD and 116 of late-onset UCD. Two cases of ornithine transcarbamylase (OTC) deficiency in males and 2 cases of argininosuccinase (AL) deficiency were diagnosed prospectively. By far the most common disorder was OTC deficiency, accounting for 2/3 of all cases. At the end of 1995, the 5-year survival rate was 22% for the neonatal-onset type and 41% for the late-onset type. Among the 20 long-term survivors with neonatal-onset UCD, 18 (90%) had moderate to severe neurodevelopmental deficits; this contrasts with 13 of 47 (28%) survivors with the late-onset type. In analysing 108 UCD cases, peak blood ammonia level during the first hyperammonaemic attack was correlated with neurodevelopmental outcome. When the concentration of blood ammonia was less than 180 mumol/L (5 times normal), there was no severe neurological damage. When the concentration of blood ammonia exceeded 350 mumol/L (10 times normal) at the first hyperammonaemic attack, the patients died or had severe neurological deficits. Our data point to the importance of early diagnosis and aggressive treatment.