Propionic acidemia

DiseaseDisorder infobox
Name = Propionic acidemia
ICD10 = ICD10|E|71|1|e|70
ICD9 = ICD9|270.3
ICDO =


Caption = Propionic acid
OMIM = 606054
MedlinePlus =
eMedicineSubj = ped
eMedicineTopic = 1906
DiseasesDB = 29673
DiseasesDB_mult = DiseasesDB2|29904

Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, [OMIM|606054] is an autosomal recessive [cite journal |pmid=10820128 |year=2000 |month=Jul |author=Ravn K, Chloupkova M, Christensen E, Brandt NJ, Simonsen H, Kraus JP, Nielsen IM, Skovby F, Schwartz M |title=High incidence of propionic acidemia in greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase |volume=67 |issue=1 |pages=203-206 |pmc=1287078 |doi=10.1086/302971 |journal=American journal of human genetics] metabolic disorder, classified as a branched-chain organic acidemia.cite journal |author=Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C |title=Methylmalonic and propionic aciduria |journal=Am J Med Genet C Semin Med Genet. |volume=142 |issue=2 |pages=104-112 |year=2006 |pmid=16602092 |doi=10.1002/ajmg.c.30090 ]

The disorder presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke.cite journal |author=Hamilton RL, Haas RH, Nyhan WC, Powell HC, Grafe MR |title=Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions |journal=Journal of Child Neurology |volume=10 |issue=1 |pages=25-30 |year=1995 |pmid=7769173 ]

Propionic Acidemia is a rare disorder that is inherited from both parents. Being autosomal recessive, neither parent shows symptoms, but both carry a defective gene responsible for this disease. It takes two faulty genes to cause PA, so there is a 1 in 4 chance for these parents to have a child with PA.

Diagnosis

Individuals with PA can not break down parts of protein and some types of fat due to a non-functioning enzyme called PCC. Without the enzyme propionyl CoA carboxylase, four essential amino acids in protein (isoleucine, valine, threonine, and methionine) are only partially processed. Too much protein causes propionic acid to build-up in the bloodstream. This in turn causes a build-up of dangerous acids and toxins, which can cause damage to the organs. In many cases, PA can damage the brain, heart, and liver, cause seizures, and delays to normal development like walking and talking. During times of illness the affected person may need to be hospitalized to prevent breakdown of proteins within the body. Each meal presents a challenge to those with PA. If not constantly monitored, the effects would be devastating. Dietary needs must be closely managed by a metabolic geneticist or metabolic dietician.

Pathophysiology

Mutations in both copies of the PCCA or PCCB genes cause propionic acidemia. [http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm http://mayoresearch.mayo.edu/mayo/research/barry_lab/ropionic-Aciademia.cfm]
Barry Lab - Vector and Virus Engineering. "Gene therapy for Propionic Acidemia"] These genes are responsible for the formation of the enzyme "propionyl-CoA carboxylase" (EC number|6.4.1.3), referred to as "PCC".

PCC is required for the normal breakdown of the essential amino acids valine, isoleucine, threonine, and methionine, as well as certain odd-chained fatty-acids. Mutations in the PCCA or PCCB genes disrupt the function of the enzyme, preventing these acids from being metabolized. As a result, propionyl-CoA, propionic acid, ketones and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia.

ymptoms

Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.

Genetic prevalence

Propionic acidemia is inherited in an autosomal recessive pattern and is found in about 1 in 35,000 live births in the United States. The condition appears to be more common in Saudi Arabia,cite journal |author=Al-Odaib AN, Abu-Amaro KK, Ozand PT, Al-Hellani AM |title=A new era for preventive genetic programs in the Arabian Peninsula |journal=Saudi Medical Journal |volume=24 |issue=11 |pages=1168-1175 |year=2003 |pmid=14647548 ] with a frequency of about 1 in 3,000. The condition also appears to be common in Amish and Mennonite populations.cite journal |author=Kidd JR, Wolf B, Hsia E, Kidd KK |title=Genetics of propionic acidemia in a Mennonite-Amish kindred |journal=Am J Hum Genet. |volume=32 |issue=2 |pages=236-245 |year=1980 |pmid=7386459 ]

References

ee also

* Methylmalonic acidemia
* Isovaleric acidemia
* Maple syrup urine disease

External links

* [http://www.pafoundation.com Propionic Acidemia Foundation]
* [http://www.oaanews.org Organic Acidemia Association]
* [http://www.paresearch.org Propionic Acidemia Research Network (PARnet)]
* [http://www.gwenforacure.com Gwen for a Cure]
*
*RareDiseases|467|Propionic acidemia
*cite web |url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=35 |title=Propionic acidemia |format= |work=Orphanet |accessdate=