Classification and goals - UCD

The urea cycle consists of six consecutive enzymatic steps and two transporters are required for the urea cycle function¹. Severe deficiency or total absence of activity of the first four enzymes (CPSI, OTC, ASS, ASL) in the urea cycle or the cofactor producer (NAGS) results in the accumulation of ammonia and other precursor metabolites during the first days of life.

The clinical presentation of hyperammonemia is very unspecific, which makes timely diagnosing highly challenging.

Disease names of UCDs and their commonly used synonyms and prevalence¹
Disease name	synonyms	Prevalance
NAGS deficiency	–	Very rare
CPS1 deficiency	–	1:62.000
OTC deficiency	–	1:14.000
ASS deficiency	Citrullinemia type 1, classic Citrullinemia	1:57.000
ASL deficiency	Argininosuccinic aciduria, ASuria	1:70.000
ARG1 deficiency	Hyperargininemia	1:350.000

The clinical presentation ranges from early onset (in the first days after birth) from a hyperammonemic crisis in severe defects to late onset of disease in less severely affected patients, which can occur at any age (including late adulthood) or with an unusual mild clinical presentation or asymptomatic.

Management aims to the establishment of anabolism and the avoidance of protein catabolism, with rapid initiation of parenteral glucose infusion and protein restriction.
Management of UCD consists of lowering of the ammonia levels by:²

Preventing protein catabolism and establishing anabolism by starting soon parenteral glucose infusion and stopping protein intake.
Reduce Nitrogen load in the urea cycle, to prevent hyperammonemia, supplement essential L-amino acids if required
Administering nitrogen scavengers
Promote normal growth and development

Clinical practice varies with respect to dietary management on the level of restriction of natural protein and amino acid supplementation.

The outcome and prognosis of these UCD disorders remain poor and depends on the duration of coma during the initial hyperammonemic decompensation(s). Patients who experienced coma for more than 24hrs often do not survive or suffer severe neurological complications.¹

References

E-IMD. Urea cycle disorders: quick reference guide. http://www.e-imd.org
Häberle J, Rubio V. Hyperammonemias and related disorders. In; Blau N (ed) Physician’s guide to the diagnosis, treatment and follow-up of inherited metabolic diseases, 2nd edn. Springer Heidelberg, 2014:47-62