Challenges in the management of an ignored cause of hyperammonemic encephalopathy: pyruvate carboxylase deficiency

Abstract

Pyruvate carboxylase (PC) deficiency is a rare autosomal recessive disease and provides clinics in three essential phenotypes. Type B PC deficiency is characterized by lactic acidosis and hyperammonemia. We report a Turkish patient who was diagnosed with type B PC deficiency. Despite the application of anaplerotic treatment with biotin, citrate and arginine-aspartate, continuous veno-venous hemodialysis (CVVHD) treatments were applied due to the failure to keep hyperammonemia and lactic acidosis under control. Ammonia values increasing to 860 μmol/L were observed. A homozygous novel variant was detected in PC gene analyses containing a 12-base pair deletion on exon 8. Although the mutation found was not reported previously, it was accepted as a pathogenic variant due to its presence in a functional region of the protein. In type B PC deficiency, although a high level of ammonia is expected, it rarely exceeds 200 μmol/L. As far as we know, the present case has the highest ammonia values in the literature. This paper has been shared to highlight to keep PC deficiency in mind regarding the differential diagnosis of hyperammonemia, particularly in the presence of lactic acidosis, and to serve as a model for the use of different modalities in the management process of PC deficiency.

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

“…Infrequently, brain damage caused by hyperammonemia cannot be ignored, especially in type B PCD. The level of ammonia in a Turkish PCD patient unexpectedly elevated to 860mM, resulting in hyperammonemic encephalopathy (21).…”

A glance at transient hyperammonemia of the newborn: Pathophysiology, diagnosis, and treatment: A review

“…[20] Increased ammonia production or insufficient ammonia detoxification can result in neonatal hyperammonemia. [21] Hyperammonemia is usually defined as >100 µmol/L in neonates or ≥50 µmol/L in term infants, children and adolescents. [22] When the blood ammonia level in a premature baby is above 150 µmol/L, investigation of possible inherited metabolic diseases is recommended.…”

Table_1.pdf

“…PCD manifests in three main clinical forms: types A, B, and C. The infantile-onset form (type-A) manifests several months after birth; it is characterized by hypotonia, failure to thrive, delayed development, and lactic acidemia, followed by infection, diarrhea, and other symptoms, which eventually result in mortality during infancy or early childhood (4,5). The neonatal-onset form (type-B) is usually characterized by severe lactic acidosis, hyperammonemia, and mortality within the first 3 months of life (6)(7)(8). The late-onset form (type C) presents with normal or mildly delayed neurological development and episodic metabolic acidosis (9,10).…”