Propionic Acidemia

This video covers propionic acidemia, an autosomal recessive organic acidemia caused by deficiency of propionyl-CoA carboxylase. We build out the metabolic pathway step by step, show where propionyl-CoA comes from, and then walk through the newborn screening findings, the characteristic labs, and full management approach. This video is intended for genetic counselors and clinical or laboratory genetics trainees who are preparing for the ABGC or ABMGG board exam. The video includes a discussion of the following topics: The genetics: autosomal recessive inheritance and the PCCA and PCCB genes, which encode the alpha and beta subunits of propionyl-CoA carboxylase The three sources of propionyl-CoA: branched-chain amino acids (valine, isoleucine, methionine, threonine), gut bacteria, and odd-chain fatty acids The downstream pathway: propionyl-CoA to methylmalonyl-CoA to succinyl-CoA and entry into the citric acid cycle Newborn screening and the elevated C3 (propionylcarnitine), plus the mimics to watch for on the exam (methylmalonic acidemia and maternal B12 deficiency) Clinical presentation: poor feeding, protein intolerance, vomiting, hypotonia, and lethargy, with family history clues such as consanguinity or a sibling who died in the neonatal period Cardiac and neurologic complications: cardiomyopathy, developmental delay, seizures, and coma related to hyperammonemia Characteristic labs: anion gap metabolic acidosis, elevated ammonia, hypoglycemia, and urine ketones ("ketotic hypoglycemia"), along with the metabolic workup (elevated C3 with low free carnitine, and urine organic acids showing propionic acid, methylcitrate, tiglylglycine, and propionylglycine) Management across three categories: dietary (low protein, low odd-chain fatty acids, low polyunsaturated fat), medical (antibiotics, bicarbonate, biotin, sodium benzoate, L-carnitine, carglumic acid, and acute dextrose), and surgical (gastrostomy tube and liver transplant) Timestamps 0:00 Introduction: what propionic acidemia is and the genetics (PCCA and PCCB) 0:27 Where propionyl-CoA comes from: amino acids, gut bacteria, and odd-chain fatty acids 1:37 Onset, incidence, and at-risk populations 1:58 Newborn screening and the elevated C3 (and its mimics) 2:26 History, physical exam, and family history clues 3:04 Cardiac and neurologic complications 3:25 Standard labs: anion gap metabolic acidosis, hyperammonemia, and hypoglycemia 4:34 Metabolic labs: acylcarnitines, urine organic acids, enzyme assay, and sequencing 5:18 Dietary management 5:54 Medical management 7:06 Surgical management More information on diagnosis and management: Propionic acidemia (GeneReviews): https://www.ncbi.nlm.nih.gov/books/NB... Propionic acidemia (MedlinePlus Genetics): https://medlineplus.gov/genetics/cond... Helpful tip: the substrates that feed into propionyl-CoA spell VOMIT: Valine, Odd-chain fatty acids, Methionine, Isoleucine, and Threonine. Fittingly, vomiting is one of the hallmark presenting features. Support our rare disease education efforts by subscribing to the StudyRare newsletter, where we share board-style questions for ABGC and ABMGG exams each month: https://studyrare.substack.com/ You can also support this channel by subscribing on YouTube, following StudyRare on LinkedIn (  / studyrare  , or buying us a coffee: https://ko-fi.com/studyrare Learn more about our work at https://www.studyrare.com Thank you! Daniel #geneticcounseling #genetics #boardexam #metabolicdisorders #organicacidemia #clinicalgenetics