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01.12.2018 | Review | Ausgabe 1/2018 Open Access

Orphanet Journal of Rare Diseases 1/2018

Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories

Orphanet Journal of Rare Diseases > Ausgabe 1/2018
Johannes Häberle, Anupam Chakrapani, Nicholas Ah Mew, Nicola Longo



The ‘classic’ organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as increased ammonia levels and accumulating toxic metabolites are associated with life-threatening neurological complications. Repeated and frequent episodes of hyperammonaemia (alongside metabolic decompensations) can result in impaired growth and intellectual disability, the severity of which increase with longer duration of hyperammonaemia. Due to the urgency required, diagnostic evaluation and initial management of patients with suspected OAs should proceed simultaneously. Paediatricians, who do not have specialist knowledge of metabolic disorders, have the challenging task of facilitating a timely diagnosis and treatment. This article outlines how the underlying pathophysiology and biochemistry of the organic acidaemias are closely linked to their clinical presentation and management, and provides practical advice for decision-making during early, acute hyperammonaemia and metabolic decompensation in neonates and infants with organic acidaemias.

Clinical management

The acute management of hyperammonaemia in organic acidaemias requires administration of intravenous calories as glucose and lipids to promote anabolism, carnitine to promote urinary excretion of urinary organic acid esters, and correction of metabolic acidosis with the substitution of bicarbonate for chloride in intravenous fluids. It may also include the administration of ammonia scavengers such as sodium benzoate or sodium phenylbutyrate. Treatment with N-carbamyl-L-glutamate can rapidly normalise ammonia levels by stimulating the first step of the urea cycle.


Our understanding of optimal treatment strategies for organic acidaemias is still evolving. Timely diagnosis is essential and best achieved by the early identification of hyperammonaemia and metabolic acidosis. Correcting metabolic imbalance and hyperammonaemia are critical to prevent brain damage in affected patients.
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