Pyruvate Carboxylase Deficiency Type C: A Rare Cause of Acute Transient Flaccid Paralysis with Ketoacidosis

Abstract

Pyruvate carboxylase (PC) is a biotin-containing enzyme that is responsible for the adenosine triphosphate-dependent carboxylation of pyruvate to oxaloacetate, a key intermediate in the tricarboxylic acid cycle. PC deficiency (OMIM 266150) is a rare autosomal recessive metabolic disease, causing elevation of pyruvate, lactate, and alanine. Three types of PC deficiency have been described in the literature; A, B, and C. Type A PC deficiency, also called infantile or North American type, is characterized by infantile onset acidosis, failure to thrive, and developmental delay. The second subtype or type B, the neonatal or French form, presents usually in the neonatal period, mostly in the first 72 hours of life with severe lactic acidosis, truncal hypotonia, and seizures. The third type is called type C, is extremely rare with few cases published in the literature. In this case report, we present an 11-month-old girl who presented with acute flaccid paralysis, lethargy, and constipation with elevated ketones and lactate. She was confirmed genetically and biochemically to have PC deficiency type C. The patient's unusual presentation expands the clinical phenotype of this extremely rare disease.

A Unique Case of Pyruvate Carboxylase Deficiency

“…Lactic acid levels vary depending on the type of PCD. Common ranges are: 2-10 mmol/L for type A, >10 mmol/L for type B, and 2-5 mmol/L for type C. The lactate/pyruvate ratio in type B is elevated (>20) while type A and C usually are normal (<20) [ 2 , 4 ]. In our patient, the lactic acid levels were between 3.5 mmol/L to 8.5 mmol/L, and the lactate/pyruvate ratio was 19, consistent with PCD type A.…”

“…Pyruvate carboxylase (PC) is a metabolic enzyme that catalyzes the irreversible carboxylation of pyruvate into oxaloacetate [ 1 ]. Pyruvate carboxylase deficiency (PCD) is a rare autosomal recessive metabolic disease with an estimated incidence of one in 250,000 births, resulting in abnormally high pyruvate, lactic acid, and alanine levels [ 2 - 3 ]. This inherited disorder is caused by a mutation in the PC gene, which results in the accumulation of toxic substances in the blood, causing multiorgan damage, especially in the nervous system [ 2 ].…”

“…Pyruvate carboxylase deficiency (PCD) is a rare autosomal recessive metabolic disease with an estimated incidence of one in 250,000 births, resulting in abnormally high pyruvate, lactic acid, and alanine levels [ 2 - 3 ]. This inherited disorder is caused by a mutation in the PC gene, which results in the accumulation of toxic substances in the blood, causing multiorgan damage, especially in the nervous system [ 2 ]. This disease can cause failure to thrive, developmental delays, motor disturbance, mental and growth retardation, seizures, and lactic acidosis starting in the neonatal or early infantile period [ 2 , 4 ].…”

“…This inherited disorder is caused by a mutation in the PC gene, which results in the accumulation of toxic substances in the blood, causing multiorgan damage, especially in the nervous system [ 2 ]. This disease can cause failure to thrive, developmental delays, motor disturbance, mental and growth retardation, seizures, and lactic acidosis starting in the neonatal or early infantile period [ 2 , 4 ].…”

“…This type is characterized by severe lactic acidosis, hyperammonemia, truncal hypotonia, coma, and liver failure [ 5 ]. Type C, the benign variety, is extremely rare, and it is characterized by a normal or slight increase in lactic acid levels, with little impact on the nervous system [ 2 , 6 ].…”