Two siblings with TFAM deficiency, a novel hepatocerebral mtDNA depletion syndrome
Major manifestations were IUGR, hypoglycemia and rapidly progressive liver failure.
Both patients had abnormal newborn screening with elevated methionine or tyrosine.
Exome sequencing uncovered a homozygous variant in TFAM in affected siblings.
Tissue studies show mtDNA depletion, decreased nucleoids and TFAM protein expression.