Neurodevelopmental outcome of long‐term therapy of urea cycle disorders in Japan

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.

Neonatal-onset carbamoyl phosphate synthetase I deficiency

“…Just as other literatures showed that most cases of CPS1D are sporadic. [1–3] Brain MRI data, which were limited in other case reports, were recorded in this case. Meanwhile, a new mutation founded in this case had not previously been described.…”

“…Severe hyperammonemia is common in neonatal-onset patients, with severe clinical manifestations and a poor prognosis. [3–5] It is easy to be misdiagnosed because of atypical symptoms, sudden onset, rapid progression and low morbidity, especially the neonatal-onset types. [1,2] Thus, clinical data, especially the brain magnetic resonance imaging (MRI) was often limited.…”

N-Carbamylglutamate Is an Effective Treatment for Acute Neonatal Hyperammonaemia in a Patient with Methylmalonic Aciduria

“…Hyperammonaemia is a medical emergency that requires urgent treatment as the total duration of coma and peak ammonia correlates with poor neurodevelopmental outcome [1,2]. Methylmalonic aciduria (MMA; OMIM # 251000) is an autosomal recessive disorder of branched-chain amino acid metabolism due to methylmalonyl-CoA mutase deficiency.…”

A case of neonatal-onset carbamoyl-phosphate synthase I deficiency treated by continuous haemodiafiltration

“…On day 19, CHDF was terminated with sodium phenylacetate, sodium benzoate and L-arginine. On day 135, he was discharged with global developmental delay (motor and verbal developmental age was at a level of approximately 3 months).Neonatal-onset fulminant CPSD remains a lethal condition [5]. Peritoneal dialysis (PD) and HD have been attempted, but PD has poor ecacy and HD for neonates is technically dicult due to the risk of disequilibrium syndrome and hypotension.…”

“…Neonatal-onset fulminant CPSD remains a lethal condition [5]. Peritoneal dialysis (PD) and HD have been attempted, but PD has poor ecacy and HD for neonates is technically dicult due to the risk of disequilibrium syndrome and hypotension.…”