Hyperammonemia

From Wikipedia, the free encyclopedia

Hyperammonemia
Classification and external resources
Ammonia
ICD-10	E72.2
ICD-9	270.6
DiseasesDB	20468
eMedicine	neuro/162 ped/1057
MeSH	D022124

Hyperammonemia (or hyperammonaemia) is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary.

Ammonia is a substance that contains nitrogen. It is a product of the catabolism of protein. It is converted to the less toxic substance urea prior to excretion in urine by the kidneys. The metabolic pathways that synthesize urea are located first in the mitochondria and then into the cytosol. The process is known as the urea cycle, which comprises several enzymes acting in sequence.

Types

Primary vs. secondary

Primary hyperammonemia is caused by several inborn errors of metabolism that are characterised by reduced activity of any of the enzymes in the urea cycle.
Secondary hyperammonemia is caused by inborn errors of intermediary metabolism characterised by reduced activity in enzymes that are not part of the urea cycle (e.g. .Propionic acidemia, Methylmalonic acidemia) or dysfunction of cells that make major contributions to metabolism (e.g. hepatic failure).

Acquired vs. Congential

Acquired hyperammonemia is usually caused by liver diseases such as viral hepatitis or excessive alcohol consumption. A Cirrhosis of the liver is formed, followed by a shunt of blood directly to the Vena Cava vane, resulting less filtration of blood in the liver, which leads to Hyperammonemia.
Congential hyperammonemia is usually due to genetic defects in one of the enzymes of the Urea cycle, which leads to lower production of Urea from Ammonia. The most common genetic defect is in Ornithine transcarbamoylase enzyme, which is X-linked.

Specific types

The following list includes such examples:

Online 'Mendelian Inheritance in Man' (OMIM) 311250 - hyperammonemia due to ornithine transcarbamylase deficiency
Online 'Mendelian Inheritance in Man' (OMIM) 606762 - hyperinsulinism-hyperammonemia syndrome (glutamate dehydrogenase 1)
Online 'Mendelian Inheritance in Man' (OMIM) 238970 - hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (ornithine translocase)
Online 'Mendelian Inheritance in Man' (OMIM) 237310 - hyperammonemia due to N-acetylglutamate synthetase deficiency
Online 'Mendelian Inheritance in Man' (OMIM) 237300 - hyperammonemia due to carbamoyl phosphate synthetase I deficiency (carbamoyl phosphate synthetase I)
Online 'Mendelian Inheritance in Man' (OMIM) 238750 - hyperlysinuria with hyperammonemia (genetics unknown)
Methylmalonic acidemia
Isovaleric acidemia
Propionic acidemia
Carnitine palmitoyltransferase II deficiency
Transient hyperammonemia of the newborn, specifically in the preterm.

Treatment

Treatment centers on limiting intake of ammonia and increasing its excretion. Dietary protein (a source of ammonium) is restricted and caloric intake is provided by glucose and fat. Intravenous arginine (argininosuccinase deficiency) sodium phenylbutyrate and sodium benzoate (ornithine transcarbamoylase deficiency) are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients with urea cycle enzyme deficiencies.^[1] Sodium phenylbutyrate and sodium benzoate can serve as alternatives to urea for the excretion of waste nitrogen. phenylbutyrate, which is the prodrug of phenylacetate, conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Similarly, sodium benzoate reduces ammonia content in the blood by conjugating with glycine to form hippuric acid, which is rapidly excreted by the kidneys.^[2] A preparation containing sodium phenylacetate and sodium benzoate is available under the trade name Ammonul. Acidification of the intestinal lumen using lactulose can decrease ammonia levels by protonating ammonia and trapping it in the stool. This is a treatment for hepatic encephalopathy.

Treatment of severe hyperammonemia (serum ammonia levels greater than 1000 μmol/L) should begin with hemodialysis if it is otherwise medically appropriate and tolerated.^[3]

Sequelae

Hyperammonemia is one of the metabolic derangements that contribute to hepatic encephalopathy.

References

↑ eMedicine - Hyperammonemia : Article by Kazi Imran Majeed
↑ Ammonul (Sodium Phenylacetate and Sodium Benzoate Injection) clinical pharmacology - prescription drugs and medications at RxList
↑ CHAPTER 298 – Inborn Errors of Metabolism and Continuous Renal Replacement Therapy in: John J. Ratey MD; Claudio Ronco MD (2008). Critical Care Nephrology: Expert Consult - Online and Print. Philadelphia: Saunders. ISBN 1-4160-4252-0. ISBN2: 9781416042525

External links

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

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

This article is issued from Wikipedia. The text is available under the Creative Commons Attribution/Share Alike; additional terms may apply for the media files.