Argininemia

Argininemia
Arginine
Classification and external resources
OMIM	207800
DiseasesDB	29677
eMedicine	ped/132
MeSH	D020162
GeneReviews	Arginase Deficiency

Argininemia, also called arginase deficiency,^[1] is an autosomal recessive^[2] urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood.

Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Diagnosis

Argininemia usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, intellectual disability, seizures, tremor, and difficulty with balance and coordination (ataxia). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.

In some affected individuals, signs and symptoms of argininemia may be less severe, and may not appear until later in life.

Genetics

Argininemia has an autosomal recessive pattern of inheritance.

Mutations in the ARG1 gene cause argininemia.

Argininemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, making a compound called urea that is excreted by the kidneys.

The ARG1 gene provides instructions for making an enzyme called arginase. This enzyme controls the final step of the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency. The accumulation of guanidino metabolites also contribute to the neurotoxicity of the disease.^[3]

This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene are required to inherit the disorder. Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder.

References

↑ Online 'Mendelian Inheritance in Man' (OMIM) 207800
↑ Uchino, Takako; Snyderman, Selma E.; Lambert, Marie; Qureshi, Ijaz A.; Shapira, Stuart K.; Sansaricq, Claude; Smit, Leonard M. E.; Jakobs, Cornelis; Matsuda, Ichiro (1995). "Molecular basis of phenotypic variation in patients with argininemia". Human Genetics 96 (3): 255–60. doi:10.1007/BF00210403. PMID 7649538.
↑ Deignan, Joshua L.; Marescau, Bart; Livesay, Justin C.; Iyer, Ramaswamy K.; De Deyn, Peter P.; Cederbaum, Stephen D.; Grody, Wayne W. (2008). "Increased plasma and tissue guanidino compounds in a mouse model of hyperargininemia". Molecular Genetics and Metabolism 93 (2): 172–8. doi:10.1016/j.ymgme.2007.09.016. PMID 17997338.

External links

GeneReviews/NCBI/NIH/UW entry on Urea Cycle Disorders Overview
GeneReviews/NCBI/NIH/UW entry on Arginase Deficiency or Hyperargininemia
OMIM entries on Arginase Deficiency
Argininemia at NLM Genetics Home Reference

Inborn error of amino acid metabolism (E70–E72, 270)

K→acetyl-CoA

Lysine/straight chain	Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria

Leucine	3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease

Tryptophan	Hypertryptophanemia

G→pyruvate→citrate

Glycine	D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy

G→glutamate→
α-ketoglutarate

Histidine	Carnosinemia Histidinemia Urocanic aciduria

Proline	Hyperprolinemia Prolidase deficiency

Glutamate/glutamine	SSADHD

G→propionyl-CoA→
succinyl-CoA

Valine	Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease

Isoleucine	2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease

Methionine	Cystathioninuria Homocystinuria Hypermethioninemia

General BC/OA	Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia

G→fumarate

Phenylalanine/tyrosine

Phenylketonuria	6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency

Tyrosinemia	Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria

Tyrosine→Melanin	Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome

Tyrosine→Norepinephrine	Dopamine beta hydroxylase deficiency reverse: Brunner syndrome

G→oxaloacetate

Urea cycle/Hyperammonemia (arginine aspartate)	Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency

Transport/
IE of RTT

Other

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