Organic acidaemias — formative SAQs

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

Prompt

Organic acidaemias

SAQ 1 (10 marks)

A term male infant is well at birth but at 60 hours of age becomes lethargic, vomits repeatedly, is hypotonic, and has a generalised seizure. Blood gas shows a pH 7.18, bicarbonate 10, and a high anion gap of 24, with moderate ketosis and a lactate of 5.2 mmol/L. The ammonia returns at 280 micromoles per litre. Sepsis cultures are pending. ^[1] ^[3]

a) Explain why this picture of a well neonate deteriorating 24 to 72 hours into feeds with a high-anion-gap metabolic acidosis and ketosis is a classic organic acidaemia presentation, and contrast the acid-base profile with that of a urea cycle disorder. (3 marks) ^[1]

b) Describe the first-tier metabolic panel you order to identify the accumulating organic acid, and explain how the acylcarnitine profile and urinary organic acids distinguish propionic acidaemia, methylmalonic acidaemia and isovaleric acidaemia. (3 marks) ^[1]

c) Outline the role of L-carnitine, calorie loading, and extracorporeal removal in this child, including the ammonia and acidosis severity that would prompt haemofiltration. (2 marks) ^[1]

d) Discuss the prognostic significance of the number and severity of acute decompensations, and outline the family emergency sick-day plan that prevents recurrence. (2 marks) ^[3]

References5Show

[1]Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, 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
[10]Schumann A, Belche V, Schaller K, Grünert SC, et al. Mitochondrial damage in renal epithelial cells is potentiated by protein exposure in propionic aciduria. J Inherit Metab Dis, 2021.PMID 34297429

Organic acidaemias — formative SAQs

SAQ 1 (10 marks)

c) Outline the role of L-carnitine, calorie loading, and extracorporeal removal in this child, including the ammonia and acidosis severity that would prompt haemofiltration. (2 marks) ^[1]

d) Discuss the prognostic significance of the number and severity of acute decompensations, and outline the family emergency sick-day plan that prevents recurrence. (2 marks) ^[3]

References5Show

[1]Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, 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
[10]Schumann A, Belche V, Schaller K, Grünert SC, et al. Mitochondrial damage in renal epithelial cells is potentiated by protein exposure in propionic aciduria. J Inherit Metab Dis, 2021.PMID 34297429