Case Report: Prenatal neurological injury in a neonate with pyruvate carboxylase deficiency type B

Abstract

BackgroundPyruvate carboxylase (PC) is a key enzyme for gluconeogenesis. PC deficiency (PCD) is an extremely rare autosomal recessive metabolic disease and is divided into three types. Type B PCD is clinically featured by lactic acidosis, hyperammonemia, hypercitrullinemia, hypotonia, abnormal movement, and seizures.Case presentationHere, we report the first case of type B PCD in China, presenting with intractable lactic acidosis shortly after birth. A compound heterozygous mutation in the PC gene was identified by whole-exome sequencing, NM_001040716.2: c.1154_1155del and c.152G>A, which were inherited from her asymptomatic parents, respectively. Furthermore, prenatal neuroradiological presentations including widened posterior horns of lateral ventricles, huge subependymal cysts, and increased biparietal diameter and head circumference were concerned. Symptomatic treatment was taken and the infant died at 26 days.ConclusionTo our knowledge, this is the minimum gestational age (22w5d) that’s when the prenatal onset of the neuroradiologic phenotype of PCD was observed. PCD has a poor prognosis and lacks an effective treatment, so this paper is shared to highlight the importance of PCD prenatal diagnosis in the absence of family history.

Clinical, biochemical, and molecular profiles of three Sri Lankan neonates with pyruvate carboxylase deficiency

“…All three patients described in the resent case series exhibited several abnormalities in the general biochemical investigations such as elevated serum bilirubin, aspartate transaminase, alkaline phosphatase and creatine kinase. Interestingly similar findings were reported by case report of a neonate with PCD type B [ 19 ].…”

“…Hyperammonemia is also a metabolic phenotype of PCD type B [ 18 ]. Increased tyrosine level observed in patient 1 is a less commonly reported finding in PCD type B [ 19 ].…”

“…High lactate, 4-hydroxyphenylacetate and 4-hydroxyphenyllactate were a constant finding in the urine organic acid profiles of all three patients. Elevated urinary 4-hydroxyphenylacetate and 4-hydroxyphenyllactate levels have been revealed by a recent case report [ 19 ]. In addition, ketotic compounds were in moderate amounts with low levels of tricarboxylic acid compounds.…”

Perfiles clínicos, bioquímicos y moleculares de tres neonatos de Sri Lanka con déficit de piruvato carboxilasa

“…La hiperamonemia es también un fenotipo metabólico de la DPC tipo B [ 18 ]. Por el contrario, la elevación de la tirosina que presentaba el paciente 1 no se suele observar en la DPC tipo B [ 19 ].…”

“…Los niveles elevados de lactato, 4-hidroxifenilacetato y 4-hidroxifenillactato fueron un hallazgo constante en los perfiles de ácidos orgánicos en orina de los tres pacientes. Este hallazgo concuerda con un caso clínico publicado recientemente, en el que se describían niveles elevados de 4-hidroxifenilacetato y 4-hidroxifenillactato en orina [ 19 ]. Esto podría indicar una inhibición secundaria en el catabolismo de la tirosina.…”