Format

Send to:

Choose Destination

Links from PubMed

Propionic acidemia(PROP)

MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
Synonyms: Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; PCC deficiency; PROP; Propionyl-CoA carboxylase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Propionic acidemia (69080001); Propionyl-CoA carboxylase deficiency (69080001); PCC - Propionyl-CoA carboxylase deficiency (69080001); Deficiency of propionyl-CoA carboxylase (124718009); Deficiency of propionyl-coenzyme A carboxylase (124718009); Hyperglycinemia with ketosis and leukopenia (69080001); Ketotic glycinemia (69080001); Ketotic hyperglycinemia (69080001)
 
Genes (locations): PCCA (13q32.3); PCCB (3q22.3)
OMIM®: 606054
HPO: HP:0003571
Orphanet: ORPHA35

Disease characteristics

Excerpted from the GeneReview: Propionic Acidemia
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by a healthy newborn with poor feeding and decreased arousal in the first few days of life, followed by progressive encephalopathy of unexplained origin. Without prompt diagnosis and management, this is followed by progressive encephalopathy manifesting as lethargy, seizures, or coma that can result in death. It is frequently accompanied by metabolic acidosis with anion gap, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Individuals with late-onset PA may remain asymptomatic and suffer a metabolic crisis under catabolic stress (e.g., illness, surgery, fasting) or may experience a more insidious onset with the development of multiorgan complications including vomiting, protein intolerance, failure to thrive, hypotonia, developmental delays or regression, movement disorders, or cardiomyopathy. Isolated cardiomyopathy can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure. [from GeneReviews]
Authors:
Oleg A Shchelochkov  |  Nuria Carrillo  |  Charles Venditti   view full author information

Additional description

From GHR
Propionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.In most cases, the features of propionic acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death.Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time. Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections.  https://ghr.nlm.nih.gov/condition/propionic-acidemia

Clinical features

Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Constipation means that a person has three or fewer bowel movements in a week. The stool can be hard and dry. Sometimes it is painful to pass. At one time or another, almost everyone gets constipated. In most cases, it lasts a short time and is not serious. . There are many things you can do to prevent constipation. They include - Eating more fruits, vegetables and grains, which are high in fiber. - Drinking plenty of water and other liquids. - Getting enough exercise. - Taking time to have a bowel movement when you need to. - Using laxatives only if your doctor says you should. - Asking your doctor if medicines you take may cause constipation. . It's not important that you have a bowel movement every day. If your bowel habits change, however, check with your doctor. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Pancreatitis
MedGen UID:
14586
Concept ID:
C0030305
Disease or Syndrome
The pancreas is a large gland behind the stomach and close to the first part of the small intestine. It secretes digestive juices into the small intestine through a tube called the pancreatic duct. The pancreas also releases the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is serious and can lead to complications. Acute pancreatitis occurs suddenly and usually goes away in a few days with treatment. It is often caused by gallstones. Common symptoms are severe pain in the upper abdomen, nausea, and vomiting. Treatment is usually a few days in the hospital for intravenous (IV) fluids, antibiotics, and medicines to relieve pain. Chronic pancreatitis does not heal or improve. It gets worse over time and leads to permanent damage. The most common cause is heavy alcohol use. Other causes include cystic fibrosis and other inherited disorders, high levels of calcium or fats in the blood, some medicines, and autoimmune conditions. Symptoms include nausea, vomiting, weight loss, and oily stools. Treatment may also be a few days in the hospital for intravenous (IV) fluids, medicines to relieve pain, and nutritional support. After that, you may need to start taking enzymes and eat a special diet. It is also important to not smoke or drink alcohol. NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Poor appetite
MedGen UID:
68562
Concept ID:
C0232462
Sign or Symptom
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Pathologic Function
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Muscular hypotonia of the trunk
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
Hypoglycemia means low blood glucose, or blood sugar. Your body needs glucose to have enough energy. After you eat, your blood absorbs glucose. If you eat more sugar than your body needs, your muscles, and liver store the extra. When your blood sugar begins to fall, a hormone tells your liver to release glucose. In most people, this raises blood sugar. If it doesn't, you have hypoglycemia, and your blood sugar can be dangerously low. Signs include . -Hunger. -Shakiness. -Dizziness. -Confusion. -Difficulty speaking. -Feeling anxious or weak. In people with diabetes, hypoglycemia is often a side effect of diabetes medicines. Eating or drinking something with carbohydrates can help. If it happens often, your health care provider may need to change your treatment plan. You can also have low blood sugar without having diabetes. Causes include certain medicines or diseases, hormone or enzyme deficiencies, and tumors. Laboratory tests can help find the cause. The kind of treatment depends on why you have low blood sugar. NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Hyperammonaemia
MedGen UID:
113136
Concept ID:
C0220994
Pathologic Function
Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.
Hyperglycinemia
MedGen UID:
82817
Concept ID:
C0268559
Disease or Syndrome
An elevated concentration of glycine in the blood.
Hyperglycinuria
MedGen UID:
107456
Concept ID:
C0543541
Disease or Syndrome
The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070).

Conditions with this feature

Propionic acidemia
MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by a healthy newborn with poor feeding and decreased arousal in the first few days of life, followed by progressive encephalopathy of unexplained origin. Without prompt diagnosis and management, this is followed by progressive encephalopathy manifesting as lethargy, seizures, or coma that can result in death. It is frequently accompanied by metabolic acidosis with anion gap, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Individuals with late-onset PA may remain asymptomatic and suffer a metabolic crisis under catabolic stress (e.g., illness, surgery, fasting) or may experience a more insidious onset with the development of multiorgan complications including vomiting, protein intolerance, failure to thrive, hypotonia, developmental delays or regression, movement disorders, or cardiomyopathy. Isolated cardiomyopathy can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure.
3-methylcrotonyl CoA carboxylase 2 deficiency
MedGen UID:
347898
Concept ID:
C1859499
Disease or Syndrome
3-methylcrotonyl-CoA carboxylase deficiency (also known as 3-MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have a shortage of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine.Infants with 3-MCC deficiency appear normal at birth but usually develop signs and symptoms in infancy or early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Many of these complications can be prevented with early detection and lifelong management with a low-protein diet and appropriate supplements. Some people with gene mutations that cause 3-MCC deficiency never experience any signs or symptoms of the condition.The characteristic features of 3-MCC deficiency are similar to those of Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

Recent clinical studies

Etiology

Arrizza C, De Gottardi A, Foglia E, Baumgartner M, Gautschi M, Nuoffer JM
Transpl Int 2015 Dec;28(12):1447-50. Epub 2015 Sep 11 doi: 10.1111/tri.12677. PMID: 26358860
Chapman KA, Bush WS, Zhang Z
Mol Genet Metab 2015 Aug;115(4):174-9. Epub 2015 May 8 doi: 10.1016/j.ymgme.2015.05.004. PMID: 25963861Free PMC Article
Zayed H
Gene 2015 Jun 15;564(2):119-24. Epub 2015 Apr 9 doi: 10.1016/j.gene.2015.04.019. PMID: 25865301
Grünert SC, Müllerleile S, De Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer R, Bodamer OA, Baumgartner MR, Brunner-Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Sperl W, Kraus JP, Superti-Furga A, Schwab KO, Sass JO
Orphanet J Rare Dis 2013 Jan 10;8:6. doi: 10.1186/1750-1172-8-6. PMID: 23305374Free PMC Article
Pena L, Franks J, Chapman KA, Gropman A, Ah Mew N, Chakrapani A, Island E, MacLeod E, Matern D, Smith B, Stagni K, Sutton VR, Ueda K, Urv T, Venditti C, Enns GM, Summar ML
Mol Genet Metab 2012 Jan;105(1):5-9. Epub 2011 Sep 22 doi: 10.1016/j.ymgme.2011.09.022. PMID: 21986446

Diagnosis

Honda M, Sakamoto S, Sakamoto R, Matsumoto S, Irie T, Uchida K, Shimata K, Kawabata S, Isono K, Hayashida S, Yamamoto H, Endo F, Inomata Y
Pediatr Transplant 2016 Sep;20(6):840-5. Epub 2016 Jul 20 doi: 10.1111/petr.12722. PMID: 27436684
Kasapkara CS, Akar M, Yürük Yıldırım ZN, Tüzün H, Kanar B, Ozbek MN
Ren Fail 2014 Apr;36(3):451-2. Epub 2013 Dec 11 doi: 10.3109/0886022X.2013.865484. PMID: 24329397
Grünert SC, Müllerleile S, De Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer R, Bodamer OA, Baumgartner MR, Brunner-Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Sperl W, Kraus JP, Superti-Furga A, Schwab KO, Sass JO
Orphanet J Rare Dis 2013 Jan 10;8:6. doi: 10.1186/1750-1172-8-6. PMID: 23305374Free PMC Article
Kandel A, Amatya SK, Yeh EA
J Child Neurol 2013 Jan;28(1):128-31. Epub 2012 Apr 24 doi: 10.1177/0883073812441057. PMID: 22532545
Lam C, Desviat LR, Perez-Cerdá C, Ugarte M, Barshop BA, Cederbaum S
Mol Genet Metab 2011 Aug;103(4):338-40. Epub 2011 Apr 22 doi: 10.1016/j.ymgme.2011.04.007. PMID: 21549625

Therapy

Charbit-Henrion F, Lacaille F, McKiernan P, Girard M, de Lonlay P, Valayannopoulos V, Ottolenghi C, Chakrapani A, Preece M, Sharif K, Chardot C, Hubert P, Dupic L
Am J Transplant 2015 Mar;15(3):786-91. Epub 2015 Feb 12 doi: 10.1111/ajt.13027. PMID: 25683683
Guenzel AJ, Hillestad ML, Matern D, Barry MA
Hum Gene Ther 2014 Sep;25(9):837-43. Epub 2014 Aug 21 doi: 10.1089/hum.2014.012. PMID: 25046265Free PMC Article
Rafique M
Arq Bras Endocrinol Metabol 2014 Apr;58(3):237-42. PMID: 24863085
Dejean de la Bâtie C, Barbier V, Valayannopoulos V, Touati G, Maltret A, Brassier A, Arnoux JB, Grévent D, Chadefaux B, Ottolenghi C, Canouï P, de Lonlay P
J Child Neurol 2014 Feb;29(2):274-9. Epub 2013 Dec 11 doi: 10.1177/0883073813508812. PMID: 24334345
Zwickler T, Riderer A, Haege G, Hoffmann GF, Kölker S, Burgard P
J Inherit Metab Dis 2014 Jan;37(1):31-7. Epub 2013 Jun 25 doi: 10.1007/s10545-013-9621-3. PMID: 23797949

Prognosis

Honda M, Sakamoto S, Sakamoto R, Matsumoto S, Irie T, Uchida K, Shimata K, Kawabata S, Isono K, Hayashida S, Yamamoto H, Endo F, Inomata Y
Pediatr Transplant 2016 Sep;20(6):840-5. Epub 2016 Jul 20 doi: 10.1111/petr.12722. PMID: 27436684
Arrizza C, De Gottardi A, Foglia E, Baumgartner M, Gautschi M, Nuoffer JM
Transpl Int 2015 Dec;28(12):1447-50. Epub 2015 Sep 11 doi: 10.1111/tri.12677. PMID: 26358860
Kasapkara CS, Akar M, Yürük Yıldırım ZN, Tüzün H, Kanar B, Ozbek MN
Ren Fail 2014 Apr;36(3):451-2. Epub 2013 Dec 11 doi: 10.3109/0886022X.2013.865484. PMID: 24329397
Grünert SC, Müllerleile S, De Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer R, Bodamer OA, Baumgartner MR, Brunner-Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Sperl W, Kraus JP, Superti-Furga A, Schwab KO, Sass JO
Orphanet J Rare Dis 2013 Jan 10;8:6. doi: 10.1186/1750-1172-8-6. PMID: 23305374Free PMC Article
Sánchez-Alcudia R, Pérez B, Ugarte M, Desviat LR
Hum Mutat 2012 Jun;33(6):973-80. Epub 2012 Apr 16 doi: 10.1002/humu.22047. PMID: 22334403

Clinical prediction guides

Chapman KA, Bush WS, Zhang Z
Mol Genet Metab 2015 Aug;115(4):174-9. Epub 2015 May 8 doi: 10.1016/j.ymgme.2015.05.004. PMID: 25963861Free PMC Article
Zayed H
Gene 2015 Jun 15;564(2):119-24. Epub 2015 Apr 9 doi: 10.1016/j.gene.2015.04.019. PMID: 25865301
Gallego-Villar L, Pérez B, Ugarte M, Desviat LR, Richard E
Biochem Biophys Res Commun 2014 Sep 26;452(3):457-61. Epub 2014 Aug 23 doi: 10.1016/j.bbrc.2014.08.091. PMID: 25159844
Sánchez-Alcudia R, Pérez B, Ugarte M, Desviat LR
Hum Mutat 2012 Jun;33(6):973-80. Epub 2012 Apr 16 doi: 10.1002/humu.22047. PMID: 22334403
Shuaib T, Al-Hashmi N, Ghaziuddin M, Megdad E, Abebe D, Al-Saif A, Doubi A, Aldhalaan H, Abouzied ME, Al-Owain M
J Child Neurol 2012 Jun;27(6):799-803. Epub 2011 Dec 7 doi: 10.1177/0883073811426929. PMID: 22156789

Recent systematic reviews

Sutton VR, Chapman KA, Gropman AL, MacLeod E, Stagni K, Summar ML, Ueda K, Ah Mew N, Franks J, Island E, Matern D, Peña L, Smith B, Urv T, Venditti C, Chakarapani A
Mol Genet Metab 2012 Jan;105(1):26-33. Epub 2011 Sep 10 doi: 10.1016/j.ymgme.2011.08.034. PMID: 21963082
Filiano JJ, Bellimer SG, Kunz PL
Pediatr Neurol 2002 Mar;26(3):201-4. PMID: 11955927

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center