Clinical experience with N-carbamylglutamate in a single-centre cohort of patients with propionic and methylmalonic aciduria

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• 作者：Alberto Burlina ; ^{alberto.burlina@unipd.it" class="auth_mail" title="E-mail the corresponding author} ; Chiara Cazzorla ; Elisa Zanonato ; Emanuela Viggiano ; Ilaria Fasan ; Giulia Polo
• 关键词：Metabolic decompensation ; Methylmalonic aciduria ; N-carbamylglutamate ; Organic acidurias ; Propionic aciduria
• 刊名：Molecular Genetics and Metabolism Reports
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：8
• 期：Complete
• 页码：34-40
• 全文大小：492 K

文摘

The effect of long-term N-carbamylglutamate (NCG) treatment on the rate and severity of decompensations due to propionic aciduria (PA) and methylmalonic aciduria (MMA) is unknown. This paper presents clinical experience from a single-centre cohort of patients with PA and MMA who received continuous long-term treatment with NCG.

Methods

The effect of oral NCG treatment (initial dose: 50 mg/kg/day) was investigated in patients with PA or MMA who were experiencing frequent progressive episodes of metabolic decompensation, who had pathological levels of ammonia, and who were referred to the Division of Metabolic Diseases, University Hospital of Padova between August 2014 and December 2015. Clinical and biochemical data, including the number of metabolic decompensations, lactic acid, uric acid and plasma ammonia levels, protein intake and body weight, were collected before and after the initiation of NCG treatment.

Results

Eight patients with PA (n = 4) and MMA (n = 4) aged 2–20 years were treated with NCG (50 mg/kg/day) for 7–16 months. Metabolic decompensation episodes decreased in number and severity, with three of the patients having no episodes (pre-treatment: 24 episodes; post-treatment: 9 episodes). After NCG treatment, all episodes were treated at home and none required hospitalisation, lactic acid values were 1.3–2.1 mmol/L and uric acid values were 0.21–0.36 mmol/L. Significant reductions in blood ammonia levels after NCG initiation were observed in five patients, whereas levels were reduced or maintained in the normal range in the remainder. Over the treatment period, patients had an increase in natural protein intake of 20–50% and gained 0–6.5 kg in bodyweight.

Conclusion

These observations suggest that, in addition to short-term benefits for the acute treatment of hyperammonaemia, NCG may be effective and well tolerated as a long-term treatment in patients with severe PA and MMA, and that further prospective studies are warranted.