Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects

Pyruvate carboxylase (PC) deficiency is a rare metabolic disease. Recently, therapeutic possibilities have been introduced. We aimed to report the largest series of the B type of PC deficiency, focusing on some neurological aspects that have not yet been documented.

We retrospectively studied nine patients with the severe neonatal form of PC deficiency diagnosed in our hospital. Detailed clinical features, brain imaging, biochemical characteristics, and global outcome are reported.

All patients had axial hypotonia and tachypnea during the first hours of life. The initial level of consciousness was preserved in most patients. Abnormal movements (high-amplitude tremor and hypokinesia) and bizarre ocular behavior were the most common findings, whereas epilepsy was infrequent. Brain magnetic resonance imaging mostly disclosed cystic periventricular leukomalacia. Hypoglycemia, lactic acidosis, and hypercitrullinemia were invariably found. Hyperammoniemia, hypernatremia, and high proline and lysine were frequently detected. A rapid fatal outcome was observed in most patients.

Clinical and biochemical characteristics of this deficiency are highly suggestive. Abnormal movements such as rigidity and hypokinesia (hypokinetic-rigid syndrome) are an important hallmark and may orientate to PC deficiency when associated with severe lactic acidosis.