Summary about Disease
Propionyl-CoA carboxylase (PCC) deficiency is a rare inherited metabolic disorder. It is caused by a defect in the enzyme propionyl-CoA carboxylase, which is essential for the breakdown of certain amino acids, odd-chain fatty acids, and cholesterol. Without sufficient functional PCC enzyme, these substances build up in the body, leading to various health problems, primarily affecting newborns and infants. It falls under the umbrella of organic acidemias.
Symptoms
Symptoms can vary in severity. In severe cases, which usually present in infancy, symptoms may include:
Poor feeding
Vomiting
Lethargy
Hypotonia (floppy muscle tone)
Developmental delay
Seizures
Metabolic acidosis (increased acidity of body fluids)
Hyperammonemia (elevated ammonia levels in the blood)
Coma Milder forms may present later in life with less severe symptoms. Some individuals may remain asymptomatic until triggered by stress, illness, or dietary changes.
Causes
PCC deficiency is caused by mutations in the PCCA or *PCCB* genes. These genes provide instructions for making the two subunits of the propionyl-CoA carboxylase enzyme. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Treatment focuses on managing symptoms and preventing metabolic crises. Specific medications may include:
Carnitine: Helps to remove propionyl-CoA from the body.
Antibiotics: To reduce propionate production by gut bacteria.
Sodium benzoate/sodium phenylacetate: To help reduce elevated ammonia levels.
Biotin: While PCC isn't a biotin-dependent enzyme, biotin supplementation may be tried empirically in some cases.
Insulin and Glucose: To manage metabolic acidosis and hyperammonemia. The primary treatment involves a strict diet limiting the intake of protein (particularly the amino acids isoleucine, valine, methionine, and threonine), odd-chain fatty acids, and cholesterol. Special medical formulas are often required.
Is Communicable
No, propionyl-CoA carboxylase deficiency is not communicable. It is a genetic disorder inherited from parents and cannot be spread from person to person.
Precautions
Precautions are aimed at preventing metabolic crises and managing the condition:
Dietary Management: Strict adherence to a prescribed low-protein diet and avoidance of fasting.
Emergency Protocol: Parents should be educated on recognizing early symptoms of metabolic decompensation (e.g., vomiting, lethargy) and have an emergency protocol in place, including a "sick day" plan involving increased carbohydrate intake.
Regular Monitoring: Regular blood and urine tests to monitor metabolite levels and overall health.
Genetic Counseling: For families with a history of PCC deficiency, genetic counseling is recommended to assess the risk of recurrence in future pregnancies.
Prompt Medical Attention: During illness or stress, affected individuals should seek prompt medical attention to prevent metabolic crises.
How long does an outbreak last?
PCC deficiency does not have outbreaks in the traditional sense of infectious diseases. However, a "metabolic crisis" or decompensation can occur due to illness, stress, dietary indiscretion, or fasting. The duration of a metabolic crisis varies depending on the severity, promptness of treatment, and individual response. It can last from several hours to several days.
How is it diagnosed?
Diagnosis involves a combination of clinical assessment and laboratory tests:
Newborn Screening: Many states include screening for PCC deficiency in their newborn screening programs.
Urine Organic Acid Analysis: Elevated levels of specific organic acids (e.g., 3-hydroxypropionic acid, methylcitric acid) in the urine are suggestive of PCC deficiency.
Plasma Amino Acid Analysis: Abnormal amino acid profiles may be present.
Acylcarnitine Profile: Elevated levels of propionylcarnitine (C3) may be detected.
Enzyme Assay: Measurement of propionyl-CoA carboxylase enzyme activity in cultured fibroblasts or leukocytes.
Genetic Testing: Confirmation of the diagnosis through molecular genetic testing of the PCCA and *PCCB* genes.
Timeline of Symptoms
Neonatal Period/Infancy (Severe Cases): Symptoms typically manifest within days or weeks of birth. Poor feeding, vomiting, lethargy, hypotonia, and respiratory distress are common early signs. Rapid progression to seizures, metabolic acidosis, hyperammonemia, and coma can occur if left untreated.
Later Infancy/Childhood (Milder Cases): Symptoms may be less severe and present later in infancy or childhood. Developmental delay, failure to thrive, and intermittent episodes of vomiting or lethargy during illness are possible.
Adulthood (Rare): Some individuals with milder forms may remain asymptomatic until adulthood, with symptoms triggered by stress, pregnancy, or dietary changes.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis and management are crucial to minimize long-term complications, such as neurological damage, developmental delay, and intellectual disability.
Lifelong Management: PCC deficiency requires lifelong management, including dietary restrictions, medical monitoring, and prompt treatment of metabolic crises.
Multidisciplinary Care: Management involves a multidisciplinary team, including a metabolic specialist, dietician, genetic counselor, and other healthcare professionals.
Carrier Screening and Prenatal Diagnosis: Carrier screening for at-risk couples and prenatal diagnosis for pregnancies at risk are available.
Psychosocial Support: Families affected by PCC deficiency may benefit from psychosocial support to cope with the challenges of managing a chronic metabolic disorder.