Genetics of Pyruvate Carboxylase Deficiency Clinical Presentation

Updated: Mar 15, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Presentation

History

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.

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Physical

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.

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Causes

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.

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