Urea cycle disorders

Urea cycle disorders (UCD) is a group of diseases with impaired urea synthesis. An accumulation of ammonia ensues. Because of ammonia's neurotoxicity, neurological symptoms and cognitive disorders are observed in these patients. Life-threatening metabolic decompensations may occur if undetected or no properly treated.

Epidemiology

The prevalence of inborn errors of urea metabolism is estimated 1:8,200-39,000.[Error: Macro 'ref' doesn't exist]

Pathogenesis

The urea cycle is a metabolic process by which ammonia, the end product of protein catabolism, is converted into a less toxic substance, urea, that can easily eliminated by the kidneys. Dysfunction of this cycle results in ammonia accumulation and depending on the defect some intermediates may accumulate too. Based on these metabolites early laboratory diagnosis is possible.

The picture below shows the urea cycle with all the enzymes (red oval) and transporters (green box) involved.

Systematic

Hereditary metabolic diseases
	Coenzyme Q10 deficiency
	Congenital disorder of glycosylation
	Disorders of cobalamin metabolism
	Disorders of iron metabolism
	Disorders of urate metabolism
	Disturbances in phosphate metabolism
	Disturbances of glucose metabolism
	Food intolerance
	Genetic hyperbilirubinemia
	Glycolipidosis
	HADH deficiency
	Hereditary disorders protein metabolism
	Hereditary lipid disorders
	Hypercatabolic hypoproteinemia
	Hyperzincemia and hypercalprotectinemia
	Hypomagnesemia
	Hypomethylation syndrome
	Lysosomal storage disease
	MELAS syndrome
	Methionine adenosyltransferase deficiency
	Methylmalonic aciduria
	Urea cycle disorders
		Argininosuccinic aciduria
			ASL
		Citrullinemia
			Citrullinemia type 1
				ASS1
			Citrullinemia type 2
				SLC25A13
		Citrullinemia type 2
			SLC25A13
		Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
			SLC25A15
		Ornithine aminotransferase deficiency
			OAT
		Ornithine carbamoyltransferase deficiency
			OTC

References:

1.	Keskinen P et al. (2008) Hereditary urea cycle diseases in Finland.

2.	Brusilow SW et al. (1996) Urea cycle disorders: diagnosis, pathophysiology, and therapy.

3.	Wikipedia article Wikipedia EN (Urea_cycle)