Propionic acidemia: Difference between revisions
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{{Infobox medical condition | |||
| name = Propionic acidemia | |||
| image = [[File:Propionic_acid_structure.svg|left|thumb|Propionic acid structure]] | |||
| caption = Structure of propionic acid | |||
| synonyms = Propionic aciduria | |||
| pronounce = | |||
| specialty = [[Medical genetics]] | |||
| symptoms = [[Vomiting]], [[lethargy]], [[hypotonia]], [[seizures]], [[metabolic acidosis]] | |||
| onset = [[Neonatal]] | |||
| duration = Lifelong | |||
| causes = [[Genetic mutation]] in [[PCCA]] or [[PCCB]] genes | |||
| risks = | |||
| diagnosis = [[Newborn screening]], [[blood test]], [[urine organic acid analysis]] | |||
| differential = [[Methylmalonic acidemia]], [[urea cycle disorders]] | |||
| prevention = | |||
| treatment = [[Dietary management]], [[carnitine]] supplementation, [[antibiotics]] | |||
| medication = | |||
| prognosis = Variable, can be life-threatening | |||
| frequency = 1 in 100,000 live births | |||
| deaths = | |||
}} | |||
== '''Alternate Names''' == | == '''Alternate Names''' == | ||
Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; Ketotic glycinemia; PROP; Propionicacidemia | Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; Ketotic glycinemia; PROP; Propionicacidemia | ||
== '''Definition''' == | == '''Definition''' == | ||
Propionic acidemia is an inherited condition in which the body | Propionic acidemia is an inherited condition in which the body can’t breakdown certain parts of [[proteins]] and [[fats]]. This leads to a build-up of toxic substances and to bouts of serious illness called decompensation events or [[metabolic]] crises. | ||
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== '''Summary''' == | == '''Summary''' == | ||
It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as [[Organic acid|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. | It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as [[Organic acid|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. | ||
== '''Epidemiology''' == | == '''Epidemiology''' == | ||
Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians. | Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians. | ||
== '''Cause''' == | == '''Cause''' == | ||
Mutations in the '''PCCA and PCCB genes''' cause propionic acidemia. These genes provide instructions for making two parts (subunits) of an [[enzyme]] called '''propionyl-CoA carboxylase''', which '''plays a role in the normal breakdown of proteins'''. | Mutations in the '''PCCA and PCCB genes''' cause propionic acidemia. These genes provide instructions for making two parts (subunits) of an [[enzyme]] called '''propionyl-CoA carboxylase''', which '''plays a role in the normal breakdown of proteins'''. | ||
Specifically, this enzyme helps '''process several [[amino acids]], which are the building blocks of proteins'''. Propionyl-CoA carboxylase also helps '''break down certain types of fat and [[cholesterol]] in the body'''. | Specifically, this enzyme helps '''process several [[amino acids]], which are the building blocks of proteins'''. Propionyl-CoA carboxylase also helps '''break down certain types of fat and [[cholesterol]] in the body'''. | ||
'''Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules'''. As a result, a substance called propionyl-CoA and other potentially '''harmful compounds can build up to toxic levels in the body'''. This buildup damages the brain and [[nervous system]], causing the serious health problems associated with propionic acidemia. | '''Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules'''. As a result, a substance called propionyl-CoA and other potentially '''harmful compounds can build up to toxic levels in the body'''. This buildup damages the brain and [[nervous system]], causing the serious health problems associated with propionic acidemia. | ||
== '''Inheritance''' == | |||
This condition is inherited in an [[autosomal recessive]] pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | This condition is inherited in an [[autosomal recessive]] pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | ||
== '''Signs and symptoms''' == | == '''Signs and symptoms''' == | ||
The following includes the most common signs and symptoms in people with propionic acidemia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can vary in severity. The lists do not include every symptom or feature that has been described in this condition. | The following includes the most common signs and symptoms in people with propionic acidemia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can vary in severity. The lists do not include every symptom or feature that has been described in this condition. | ||
Propionic acidemia causes episodes of illness called decompensation events caused by the build-up of toxic substances in the blood. Decompensation events are serious bouts of illness that can cause brain damage if not treated quickly. | Propionic acidemia causes episodes of illness called decompensation events caused by the build-up of toxic substances in the blood. Decompensation events are serious bouts of illness that can cause brain damage if not treated quickly. | ||
Symptoms of a decompensation event usually occur a few days after birth and may include: | Symptoms of a decompensation event usually occur a few days after birth and may include: | ||
* Poor feeding and loss of appetite | * Poor feeding and loss of appetite | ||
* Vomiting | * Vomiting | ||
* Weak muscle tone (hypotonia) | * Weak muscle tone (hypotonia) | ||
* Lack of energy (lethargy) | * Lack of energy (lethargy) | ||
* Seizures | * Seizures | ||
* Coma | * Coma | ||
Other complications may include : | Other complications may include : | ||
* Thickened heart muscle (cardiomyopathy) | * Thickened heart muscle (cardiomyopathy) | ||
| Line 50: | Line 64: | ||
* Anemia | * Anemia | ||
In the late-onset form, symptoms appear in childhood and are similar to the neonatal-onset form, but may come and go over time. | In the late-onset form, symptoms appear in childhood and are similar to the neonatal-onset form, but may come and go over time. | ||
For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. | For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. | ||
80%-99% of people have these symptoms | 80%-99% of people have these symptoms | ||
| Line 58: | Line 71: | ||
* Organic [[aciduria]] | * Organic [[aciduria]] | ||
* Propionyl-CoA carboxylase deficiency | * Propionyl-CoA carboxylase deficiency | ||
30%-79% of people have these symptoms | 30%-79% of people have these symptoms | ||
* Abnormality of immune system physiology | * Abnormality of immune system physiology | ||
| Line 65: | Line 77: | ||
* [[Hepatomegaly]](Enlarged liver) | * [[Hepatomegaly]](Enlarged liver) | ||
* [[Intellectual disability]](Mental deficiency) | * [[Intellectual disability]](Mental deficiency) | ||
5%-29% of people have these symptoms | 5%-29% of people have these symptoms | ||
* [[Cardiomyopathy]](Disease of the heart muscle) | * [[Cardiomyopathy]](Disease of the heart muscle) | ||
* Cerebellar [[hemorrhage]] | * Cerebellar [[hemorrhage]] | ||
== '''Diagnosis''' == | == '''Diagnosis''' == | ||
Propionic acidemia can be diagnosed through [[newborn screening]]. Almost every state in the United States screens for this disorder. Additional testing required for diagnosis may include:<ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. | Propionic acidemia can be diagnosed through [[newborn screening]]. Almost every state in the United States screens for this disorder. Additional testing required for diagnosis may include:<ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92946/</ref> | ||
* [[Biochemical testing]] for abnormal levels of specific chemicals | * [[Biochemical testing]] for abnormal levels of specific chemicals | ||
* [[Genetic testing]] for mutations in either the '''PCCA or PCCB gene ''' | * [[Genetic testing]] for mutations in either the '''PCCA or PCCB gene ''' | ||
* PA is caused by '''deficiency of propionyl-CoA carboxylase (PCC)''', the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Newborns with PA tested by expanded newborn screening have elevated C3 (propionylcarnitine). | * PA is caused by '''deficiency of propionyl-CoA carboxylase (PCC)''', the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Newborns with PA tested by expanded newborn screening have elevated C3 (propionylcarnitine). | ||
* Testing of urine [[organic acid]]s in persons who are symptomatic or those detected by newborn screening reveals elevated 3-hydroxypropionate and the presence of [[methylcitrate]], [[tiglylglycine]], [[propionylglycine]], and [[lactic acid]]. | * Testing of urine [[organic acid]]s in persons who are symptomatic or those detected by newborn screening reveals elevated 3-hydroxypropionate and the presence of [[methylcitrate]], [[tiglylglycine]], [[propionylglycine]], and [[lactic acid]]. | ||
* Testing of [[plasma]] amino acids reveals elevated [[glycine]]. | * Testing of [[plasma]] amino acids reveals elevated [[glycine]]. | ||
* Confirmation of the diagnosis relies on detection of biallelic pathogenic variants in PCCA or PCCB or of deficient PCC enzymatic activity. In individuals with equivocal molecular [[genetic test]] results, a combination of enzymatic and molecular diagnostics may be necessary. | * Confirmation of the diagnosis relies on detection of biallelic pathogenic variants in PCCA or PCCB or of deficient PCC enzymatic activity. In individuals with equivocal molecular [[genetic test]] results, a combination of enzymatic and molecular diagnostics may be necessary. | ||
== '''Treatment''' == | == '''Treatment''' == | ||
There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. <ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. | There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. <ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92946/</ref>[https:www.ncbi.nlm.nih.gov/books/NBK92946/]. | ||
Options include: | Options include: | ||
* Aggressive treatment of decompensation events | * Aggressive treatment of decompensation events | ||
* Special [[protein]] managed diet | * Special [[protein]] managed diet | ||
* Medications such as [[carnitine]] | * Medications such as [[carnitine]] | ||
* Avoidance of stressors (such as fasting or illness) that can lead to a decompensation event | * Avoidance of stressors (such as fasting or illness) that can lead to a decompensation event | ||
* [[Liver transplant]] in some cases | * [[Liver transplant]] in some cases | ||
Specialists that may be involved in the care of people with propionic acidemia include [1]: | |||
Specialists that may be involved in the care of people with propionic acidemia include [1]: | |||
Nutritionist | Nutritionist | ||
* Genetics professional | * Genetics professional | ||
| Line 95: | Line 102: | ||
* Neurologist | * Neurologist | ||
* Physical therapist and occupational therapist | * Physical therapist and occupational therapist | ||
== '''References''' == | == '''References''' == | ||
<references /> | <references /> | ||
{{Fatty-acid metabolism disorders}} | {{Fatty-acid metabolism disorders}} | ||
{{DEFAULTSORT:Propionic Acidemia}} | {{DEFAULTSORT:Propionic Acidemia}} | ||
[[Category:Amino acid metabolism disorders]] | [[Category:Amino acid metabolism disorders]] | ||
Latest revision as of 06:07, 8 April 2025
Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD's medical weight loss NYC, sleep center NYC
Philadelphia medical weight loss and Philadelphia sleep clinics
| Propionic acidemia | |
|---|---|
| Synonyms | Propionic aciduria |
| Pronounce | |
| Specialty | Medical genetics |
| Symptoms | Vomiting, lethargy, hypotonia, seizures, metabolic acidosis |
| Complications | N/A |
| Onset | Neonatal |
| Duration | Lifelong |
| Types | N/A |
| Causes | Genetic mutation in PCCA or PCCB genes |
| Risks | |
| Diagnosis | Newborn screening, blood test, urine organic acid analysis |
| Differential diagnosis | Methylmalonic acidemia, urea cycle disorders |
| Prevention | |
| Treatment | Dietary management, carnitine supplementation, antibiotics |
| Medication | |
| Prognosis | Variable, can be life-threatening |
| Frequency | 1 in 100,000 live births |
| Deaths | |
Alternate Names[edit]
Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; Ketotic glycinemia; PROP; Propionicacidemia
Definition[edit]
Propionic acidemia is an inherited condition in which the body can’t breakdown certain parts of proteins and fats. This leads to a build-up of toxic substances and to bouts of serious illness called decompensation events or metabolic crises.
Summary[edit]
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.
Epidemiology[edit]
Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians.
Cause[edit]
Mutations in the PCCA and PCCB genes cause propionic acidemia. These genes provide instructions for making two parts (subunits) of an enzyme called propionyl-CoA carboxylase, which plays a role in the normal breakdown of proteins. Specifically, this enzyme helps process several amino acids, which are the building blocks of proteins. Propionyl-CoA carboxylase also helps break down certain types of fat and cholesterol in the body. Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules. As a result, a substance called propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia.
Inheritance[edit]
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Signs and symptoms[edit]
The following includes the most common signs and symptoms in people with propionic acidemia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can vary in severity. The lists do not include every symptom or feature that has been described in this condition. Propionic acidemia causes episodes of illness called decompensation events caused by the build-up of toxic substances in the blood. Decompensation events are serious bouts of illness that can cause brain damage if not treated quickly. Symptoms of a decompensation event usually occur a few days after birth and may include:
- Poor feeding and loss of appetite
- Vomiting
- Weak muscle tone (hypotonia)
- Lack of energy (lethargy)
- Seizures
- Coma
Other complications may include :
- Thickened heart muscle (cardiomyopathy)
- Enlarged liver
- Intellectual and motor disability
- Movement disorders
- Poor growth
- Anemia
In the late-onset form, symptoms appear in childhood and are similar to the neonatal-onset form, but may come and go over time. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms
- Constipation
- Hyperammonemia(High blood ammonia levels)
- Hypoglycemia(Low blood sugar)
- Organic aciduria
- Propionyl-CoA carboxylase deficiency
30%-79% of people have these symptoms
- Abnormality of immune system physiology
- Arrhythmia(Abnormal heart rate)
- Global developmental delay
- Hepatomegaly(Enlarged liver)
- Intellectual disability(Mental deficiency)
5%-29% of people have these symptoms
- Cardiomyopathy(Disease of the heart muscle)
- Cerebellar hemorrhage
Diagnosis[edit]
Propionic acidemia can be diagnosed through newborn screening. Almost every state in the United States screens for this disorder. Additional testing required for diagnosis may include:<ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92946/</ref>
- Biochemical testing for abnormal levels of specific chemicals
- Genetic testing for mutations in either the PCCA or PCCB gene
- PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Newborns with PA tested by expanded newborn screening have elevated C3 (propionylcarnitine).
- Testing of urine organic acids in persons who are symptomatic or those detected by newborn screening reveals elevated 3-hydroxypropionate and the presence of methylcitrate, tiglylglycine, propionylglycine, and lactic acid.
- Testing of plasma amino acids reveals elevated glycine.
- Confirmation of the diagnosis relies on detection of biallelic pathogenic variants in PCCA or PCCB or of deficient PCC enzymatic activity. In individuals with equivocal molecular genetic test results, a combination of enzymatic and molecular diagnostics may be necessary.
Treatment[edit]
There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. <ref>Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. 2012 May 17 [Updated 2016 Oct 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92946/</ref>[https:www.ncbi.nlm.nih.gov/books/NBK92946/]. Options include:
- Aggressive treatment of decompensation events
- Special protein managed diet
- Medications such as carnitine
- Avoidance of stressors (such as fasting or illness) that can lead to a decompensation event
- Liver transplant in some cases
Specialists that may be involved in the care of people with propionic acidemia include [1]: Nutritionist
- Genetics professional
- Developmental specialist
- Neurologist
- Physical therapist and occupational therapist
References[edit]
<references />
| Inborn error of lipid metabolism: fatty-acid metabolism disorders | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
NIH genetic and rare disease info[edit]
Propionic acidemia is a rare disease.
| Rare and genetic diseases | ||||||
|---|---|---|---|---|---|---|
|
Rare diseases - Propionic acidemia
|
