Organic acidaemias — branching viva

Branching viva on the organic acidaemias: recognising the high-anion-gap metabolic acidosis that distinguishes them from the urea cycle disorders, delivering the 'treat on suspicion' emergency protocol with carnitine and toxin removal, trialling cofactor responsiveness in methylmalonic acidaemia, and locking in long-term medical and transplant-based management with family counselling.

branching clinical structured oral3 min readVerification in progress

Prompt

Neonatal unit: a term male infant, well at birth, now 48 hours old with lethargy, poor feeding, vomiting, hypotonia and seizures. Blood gas shows a high-anion-gap metabolic acidosis with ketosis and a lactate of 4.8. The ammonia returns at 310 micromoles per litre. The examiner asks: why is this an organic acidaemia rather than a urea cycle disorder or sepsis, what is the 'treat on suspicion' emergency protocol, how do acylcarnitines and urinary organic acids localise the defect, what is the toxic-organic-acid mechanism of basal-ganglia injury, and when would you use haemofiltration — then branches to the cofactor responsiveness trial in methylmalonic acidaemia, and asks you to explain the B12-responsive versus non-responsive subtypes, the role of transplantation, and the emergency sick-day plan.

Opening framework

My framework has four layers. First, the recognition — a well neonate deteriorating 24 to 72 hours into feeds with a high-anion-gap metabolic acidosis and ketosis is an organic acidaemia until proven otherwise, and the acid-base picture is the discriminator. Second, the emergency protocol — treat on suspicion: stop protein, calorie-load, give carnitine, correct the acidosis, and use haemofiltration if refractory. Third, the biochemistry — the organic acidaemias are branched-chain amino-acid catabolic blocks, and each produces a recognisable acylcarnitine and organic-acid pattern. Fourth, the cofactor responsiveness — methylmalonic acidaemia may be B12-responsive, and the trial defines the prognosis. ^[1]

References5Show

[1]Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis, 2014.PMID 25205257
[3]Nizon M, Ottolenghi C, Valayannopoulos V, Arnoux JB, et al. Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias. Orphanet J Rare Dis, 2013.PMID 24059531
[4]Boy N, Mühlhausen C, Maier EM, Ballhausen D, et al. Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision. J Inherit Metab Dis, 2023.PMID 36221165
[6]Head PE, Meier JL, Venditti CP. New insights into the pathophysiology of methylmalonic acidemia. J Inherit Metab Dis, 2023.PMID 37078237
[8]Sen K, Burrage LC, Chapman KA, Ginevic I, et al. Solid organ transplantation in methylmalonic acidemia and propionic acidemia: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med, 2023.PMID 36534118

Organic acidaemias — branching viva

branching clinical structured oral3 min readVerification in progress

Opening framework

References5Show

[1]Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis, 2014.PMID 25205257
[3]Nizon M, Ottolenghi C, Valayannopoulos V, Arnoux JB, et al. Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias. Orphanet J Rare Dis, 2013.PMID 24059531
[4]Boy N, Mühlhausen C, Maier EM, Ballhausen D, et al. Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision. J Inherit Metab Dis, 2023.PMID 36221165
[6]Head PE, Meier JL, Venditti CP. New insights into the pathophysiology of methylmalonic acidemia. J Inherit Metab Dis, 2023.PMID 37078237
[8]Sen K, Burrage LC, Chapman KA, Ginevic I, et al. Solid organ transplantation in methylmalonic acidemia and propionic acidemia: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med, 2023.PMID 36534118