Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

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.

G cluster_cell liver cell cluster_cellmem cell membrane cluster_cytoplasm cytoplasm cluster_mitochondrialmem mitochondrial membrane cluster_mitochondrion mitochondrion ornt1 ORNT1 o1 ornithine ornt1->o1 slc25a15 SLC25A15 c2 citrulline slc25a15->c2 c1 citrulline c1->slc25a15 otc OTC o1->otc cp1 carbamyl phosphate cp1->otc glut glutamate nags NAGS glut->nags acoa acetyle coenzyme A acoa->nags nag N-acetyleglutamate cps_1 CPS-I nag->cps_1 am1 ammonia am1->cps_1 bic1 bicarbonate bic1->cps_1 otc->c1 nags->nag cps_1->cp1 ass ASS c2->ass o2 ornithine o2->ornt1 slc7a7 SLC7A7 o2->slc7a7 a1 argininsuccinate asl ASL a1->asl a2 arginine arg1 ARG1 a2->arg1 a2->slc7a7 f1 fumarate u1 urea am2 ammonia am2->am1 bic2 bicarbonate bic2->bic1 asp1 aspatate ass->a1 ass->asp1 asl->a2 asl->f1 arg1->o2 arg1->u1 o3 ornithine slc7a7->o3 a3 arginine slc7a7->a3
Urea cycle in a liver cell

Systematic

Hereditary metabolic diseases
Aceruloplasminemia/Hypoceruloplasminemia
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 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.

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2.

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

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3.

Wikipedia article

Wikipedia EN (Urea_cycle) [^]
Update: May 11, 2019