Fetal for Monday, April 7th, 2025

Contributed by Cincinnati Children's Hospital & Medical Center
Bhagyashree Rathore, Betul Derinkuyu, Jungwhan Choi, Usha Nagaraj, and Beth-Kline Fath.

History

36 weeks gestational age pregnancy for evaluation of ventriculomegaly, negative TORCH testing, small for age fetal biometry.

Images (Click any image to enlarge)

Question

What is the most common genetic mutation associated with this condition?

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Correct answer

PDHA1

Discussion

Pyruvate dehydrogenase complex deficiency​ is a common cause of congenital lactic acidosis.

Pyruvate Dehydrogenase is an enzyme that links glycolysis and Kreb's cycle.

PDHA1 is the most common associated genetic mutation which encodes E1 alpha subunit.

Common described imaging findings include:

  • Germinolytic cysts
  • Abnormal white matter T2 prolongation and periventricular cysts
  • Corpus callosum dysgenesis 
  • Ventriculomegaly
  • Small pons
  • Reduced brain volumes/ small biometry for age
  • Decreased sulcation/gyration

Germinolytic cysts and corpus callosum dysgenesis with small head biometry in presence of negative TORCH screen should raise concern for Pyruvate Dehydrogenase Complex Deficiency.

Antenatal diagnosis can allow for early intervention including glucose/carbohydrate restriction, 


Differential diagnosis

  1. TORCH infections - specially CMV which commonly has microcephaly. periventricular cysts and calcifications.
  2. Zellweger's Syndrome - PEX gene mutations are most common. Periventricular and germinolytic cysts, peri-sylvian dysgyria and renal cysts are common imaging findings. Macrocephaly is seen.
  3. Aicardi-Goutières Syndrome​ - Also has microcephaly, periventricular cysts and white matter T2 prolongation which progresses to atrophy. Parenchymal and basal ganglia calcification are frequently seen. Germinolytic/caudothalamic groove cysts are not a typical feature. TREX -1 gene mutations are associated.

Additional images

References

  • Coste, T., et al. "Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype." Ultrasound in Obstetrics & Gynecology 60.6 (2022): 805-811.
  • Fortin, Olivier, et al. "Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency." medRxiv (2024).
  • Rahesh, Jasmin, et al. "Pyruvate dehydrogenase complex deficiency mimicking congenital cytomegalovirus infection on imaging." Baylor University Medical Center Proceedings. Vol. 35. No. 2. Taylor & Francis, 2022.
  • Pirot, Nathalie, et al. "Phenotypic and neuropathological characterization of fetal pyruvate dehydrogenase deficiency." Journal of Neuropathology & Experimental Neurology 75.3 (2016): 227-238.
  • Goergen, Stacy K., et al. "The fetus with ganglionic eminence abnormality: head size and extracranial sonographic findings predict genetic diagnoses and postnatal outcomes." American Journal of Neuroradiology 42.8 (2021): 1528-1534.
  • Diaz, Joana, Larry Matsumoto, and Jennifer Kucera Neville. "Prenatal diagnosis of zellweger syndrome by fetal MRI: a case report." Radiology Case Reports 16.12 (2021): 3950-3954.
  • Panigrahy, Nalinikanta, et al. "Aicardi-Goutières syndrome (AGS): recurrent fetal cardiomyopathy and pseudo-TORCH syndrome." BMJ Case Reports CP 15.12 (2022): e249192.