Propionic aciduria

Propionic acidemia (AP) is an inherited, autosomal, recessive disease caused by a deficiency of the enzyme propionyl CoA carboxylase, is an organic aciduria caused by deficiencies in the activity of propionyl CoA-carboxylase, and is characterized by life-threatening episodes of metabolic decompensation and dysfunction. neurological that can be complicated by cardiomyopathy . This enzyme is found in the mitochondria of the cell and serves to catalyze the transformation of propionyl CoA to methylmanolyl CoA, this metabolic step is part of the degradation of the amino acids valine, methionine , threonine and isoleucine., is also involved in the metabolization of those fatty acids that have an odd number of carbon atoms. Deficiency of enzyme activity causes a high concentration of propionate in urine and blood . This disorder is included in the group of diseases called congenital errors of metabolism and its frequency varies by region, in the United States there is one case for every 35,000 births, while in Saudi Arabiaaffects 1 in 3,000 born. It is inherited from parents to children in an autosomal recessive pattern, which means that parents are generally healthy, do not have the disorder, but are carriers and pass the abnormality on to their children. The child must receive a copy of the abnormal gene from each parent to present the disease. Propionic acidemia can manifest itself according to different clinical patterns, but the most common form is severe neonatal, in which symptoms appear in the first week of life and are manifested by vomiting , weight loss, neurological symptoms, loss of muscle tone and seizures, all of which can lead to coma. Laboratory tests detect metabolic acidosis and elevation of NH4 + inblood ( hyperammonemia ).


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  • 1 Epidemiology
  • 2 Clinical description
  • 3 Etiology
  • 4 Diagnostic methods
    • 1 Differential diagnosis
    • 2 Prenatal diagnosis
  • 5 Management and treatment
  • 6 Forecast
  • 7 Sources


The prevalence is probably 1 in 100,000 live births worldwide. In some countries, such as Saudi Arabia , a high prevalence rate is observed.

Clinical description

Propionic acidemia can occur in one of the following forms: severe neonatal onset, intermittent late onset, or progressive chronic form. In the severe neonatal onset form, affected children present with symptoms of metabolic intoxication (poor diet, vomiting , altered sensory), and pancytopenia in a period ranging from a few hours to weeks after birth. In the form of intermittent late onset, the disease occurs after a year or more of life with episodes of metabolic decompensation caused by periods of catabolic response to situations of stress such as fever , vomiting and trauma. Patients may also present with acute neurological crisis characterized bydystonia , rigidity, choreoathetosis and dementia (due to infarction of the basal ganglia). In the chronic progressive form, the disease presents as growth retardation, chronic vomiting , psychomotor retardation, hypotonia , seizures, and movement disorders. Other known complications are intellectual disability, optic neuropathy , cardiomyopathy , long QT syndrome , pancreatitis , dermatitis, and immune dysfunction.


AP is caused by mutations in the PCCA (13q32) or PCCB (3q21-q22) genes that encode the α and β subunits of propionyl CoA-carboxylase.

Diagnostic methods

Extended newborn screening tests identify PA by detecting an elevated level of propionylcarnitine. Symptomatic cases are presented during metabolic decompensation with acidosis , ketosis , increased anion concentration, hyperlactatemia , hyperglycinemia , hyperammonemia , hypoglycemia, and cytopenias . Urine analysis by gas chromatography-mass spectrometry reveals a characteristic pattern with 3-hydroxypropionate, methylcitrate , propionylglycine and propionylcarnitinethat persists between crises. Confirmation of the diagnosis is based on the detection of deficiencies in enzyme activity or mutations in the PCCA or PCCB genes.

Differential diagnosis

Differential diagnosis includes the neonatal sepsis, other organic acidurias branched chain, stenosis of the pylorus or other common causes of acidosis by increased anion concentration. In children chronically delayed growth, vomiting chronic and neutropenia can mimic intolerance milk of cow , the celiac disease or immune deficiencies.

Prenatal diagnosis

Prenatal diagnosis can be performed by measuring propionylcarnitine, methyl citrate, and 3-hydroxypropionate in the amniotic fluid or by DNA analysis or direct enzyme analysis in families with a known mutation.

Management and treatment

Confirmation of the diagnosis is not essential to start treatment. The main form of treatment in a crisis is to reverse catabolism by stopping protein intake and administering non-protein calories in the form of intravenous fluids. The hyperammonemia is treated by administering sodium benzoate , carbamylglutamate or hemodialysis . The regulation of nutrition , specifically protein restriction, is a fundamental element in the long-term treatment of patients with AP. Regular growth monitoring should be done. The carnitine supplementaids in detoxification. Avoiding metabolic decompensations and treating episodes promptly with standard treatment can improve intellectual performance.


Early detection and treatment lead to a reduction in the mortality rate during the first year of life and an improvement in the survival rate in early childhood and childhood, but morbidity in terms of delayed cognitive development remains high. The question of whether a liver transplant can be performed in early childhood to improve prognosis is still being investigated.


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