Novel mutation causing propionic acidemia associated with unexplained autoimmune thyrotoxicosis

Abstract

Propionic acidemia (PA) is a rare autosomal recessive inborn error of metabolism (IEM) with relatively higher prevalence in the United Arab Emirates (UAE). Absence of propionyl-CoA carboxylase (PCC) enzyme classically leads to acute decompensation in the early neonatal period. We report a novel homozygous frameshift variant c.2158_2159insT; p.Glu720Valfs*14 (NM_000282.3) in the last exon of the PCCA gene which led to a severe presentation of PA in a newborn Emirati female. Uniquely the diagnosis remained unclear since newborn screening revealed an isolated elevation in plasma proprionylcarnitine (C3) while urinary organic acids remained persistently negative for the classic biochemical abnormalities even during the period of critical illness. Additionally, the patient had an unexplained diagnosis of neonatal thyrotoxicosis. This case explores possible underlying causes through an extensive literature search. To date, there have been no similar reported cases in existing literature.

Keywords: AA, Amino Acids; C3, proprionylcarnitine; FT3/FT4, Free T3/Free T4; G-CSF, growth colony stimulating factor; HD, hemodialysis; Hyperammonemia; Hyperthyroidism; IEM, Inborn Errors of Metabolism; MMA, methlymalonic acid; MRI, Magnetic Resonance Imaging; Metabolic acidosis; Neonate; OA, Organic Acids; PA, Propionic Acidema; PCC, Propionyl-CoA Carboxylase; PICU, pediatric intensive care unit; Propionic acidemia; TPN, Total parenteral nutrition; TPO, Thyroid Peroxidase; TRAB, Thyroid Receptor Antibodies; TSH, Thyroid Stimulating Hormone; TSI, Thyroid Stimulating Immunoglobulins; Thyrotoxicosis; UAE, United Arab Emirates.