Propionic Acidemia: Case Report and Review of Neurologic Sequelae

We describe late-onset propionic acidemia in a 12-year-old boy who presented with vomiting, cough, and fever, and manifested a precipitous decline in mental status, accompanied by acute encephalopathy and severe neurologic damage, with bilateral basal ganglia involvement upon neuroimaging. He exhibited metabolic acidosis, hyperammonemia, hypocarnitinemia, and elevated plasma glycine. Urinary organic-acid analysis demonstrated very highly elevated 3-hydroxypropionate, propionylglycine, methylcitrate, and tiglylglycine, without an elevation of methylmalonate. Despite intensive medical care, this particular case proved fatal, highlighting the importance of metabolic testing in cases of acute mental-status changes and encephalopathy of unknown etiology.

Introduction

Propionic acidemia is a rare genetic deficiency of the essential mitochondrial enzyme propionyl-CoA carboxylase that clinically features metabolic acidosis, developmental delay, and neurologic abnormalities [1], [2], [3], [4]. Because mitochondria are vital to neuron survival, neurotransmission, and plasticity, dysfunction often proves devastating [5]. In early-onset propionic acidemia, patients typically present within their first 3 months of age with vomiting, hypotonia, lethargy, metabolic acidosis, seizures, and coma [1], [2]. Late-onset cases tend to run more heterogeneous courses, presenting with episodic acidosis, acute encephalopathy, mental retardation, and movement disorders, with extrapyramidal signs such as choreoathetosis and dystonia, even without metabolic decompensation [1], [2]. Hyperammonemia and hypocarnitinemia are often evident, as are elevated levels of urinary organic acids [2], [3]. Periods free of disease may intertwine with relapses induced by protein overload, infection, fever, or extended fasting [2], [4].

Although about 80% of cases arise during the neonatal period, late-onset cases are more uncommon, especially those proving fatal [2]. We present a 12-year-old boy with late-onset propionic acidemia who developed acute alterations in mental status, and who manifested remarkable encephalopathy with bilateral basal ganglia involvement. To facilitate a better understanding of propionic acidemia, a review of similar cases, neurologic sequelae, and treatments will be provided.