Log in to add personal notes on this page.
A male infant presents with dilated cardiomyopathy, neutropenia, and failure to thrive. He has recurrent bacterial infections. Urine organic acids show elevated 3-methylglutaconic acid. His maternal uncle died in infancy from heart failure.
XLR; TAFAZZIN (tafazzin, a cardiolipin remodeling enzyme)
- Cardiolipin is a phospholipid critical for mitochondrial inner membrane structure and function
- Deficient cardiolipin remodeling disrupts cristae formation and oxidative phosphorylation
- Affects boys (X-linked); carrier females are typically unaffected
- Dilated cardiomyopathy (most common presentation, can be fatal in infancy)
- Neutropenia (cyclic or persistent): risk for bacterial infections
- Skeletal myopathy (proximal weakness, exercise intolerance)
- Growth delay / failure to thrive
- 3-methylglutaconic aciduria (elevated on urine organic acids, a diagnostic clue)
- Left ventricular noncompaction may be present
- Urine organic acids: elevated 3-methylglutaconic acid (type II)
- Cardiolipin analysis (abnormal cardiolipin species on blood spot or fibroblasts)
- TAFAZZIN gene testing
- CBC showing neutropenia
- Heart failure management (ACE inhibitors, beta-blockers, diuretics)
- Cardiac transplant if refractory
- G-CSF for severe neutropenia
- Prophylactic antibiotics during neutropenic episodes
- Nutritional support
"Bart Simpson": think of Bart Simpson for Barth syndrome:
- Bart's spiky hair looks like cristae (the tight folds of mitochondrial membrane); mitochondrial membrane curvature is affected
- Cardiolipin synthesis is affected: "B-art-h affects the heart"
- Barth is X-linked, so affects boys: Bart is a boy
3-methylglutaconic aciduria: Barth is one of the "3-MGA" disorders; elevated 3-methylglutaconic acid on urine organic acids is the biochemical clue.