Genetics of Pyruvate Carboxylase Deficiency Clinical Presentation

Updated: Mar 15, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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The following are important aspects in the history of patients with pyruvate carboxylase deficiency (PCD):

  • Birth: Low Apgar scores and small size for gestational age are nonspecific symptoms of metabolic disturbance during gestation.

  • General: The development of poor feeding, vomiting, and lethargy are nonspecific but common symptoms of metabolic illnesses. If these symptoms are instigated by a mild viral illness and are more severe than would be expected, a metabolic disturbance should be considered, especially after a bacterial infection has been ruled out.

  • Development: Mental, psychomotor, and/or growth retardation are nonspecific symptoms of metabolic disease.

  • Neurologic: Poor acquisition or loss of motor milestones, new-onset seizures, episodic incoordination, abnormal eye movements, and poor response to visual stimuli are signs of poor neurologic development or degenerative disease.

  • Respiratory: A history of apnea, dyspnea, or respiratory depression is consistent with neurologic disease or severe lactic acidosis.



Neurologic findings include the following:

  • Hypotonia, ataxia, tremors, and choreoathetosis are consistent with pyruvate carboxylase deficiency.

  • Progressive motor pathway degeneration results in a present Babinski sign and spastic diplegia or quadriplegia.

  • Ophthalmologic examination may reveal poor visual tracking, grossly dysconjugate eye movements, poor pupillary response, and blindness.

  • Prenatal microcephaly or postnatal microcephaly also may be evident on physical examination.

Intermittent hyperpnea at rest, apnea, dyspnea, Cheyne-Stokes respiration, and respiratory failure are nonspecific signs of metabolic and neurologic disease or severe acidosis.

Hepatomegaly is also noted.



The gene that encodes pyruvate carboxylase (PC) has been localized to bands 11q13.4-q13.5.

An autosomal recessive inheritance pattern is characteristic.

Neonatal pyruvate carboxylase deficiency is associated with complete absence of messenger ribonucleic acid (mRNA) and the PC enzyme protein.

Infantile-onset pyruvate carboxylase deficiency is associated with a residual enzyme activity less than 2% of normal levels.