A shortfin mako shark (Isurus oxyrinchus) caught in 1996 by sportfishermen in Long Island (New York, USA) had many granulomas containing larval nematodes. Granulomas were present in the myocardium, spleen, pancreas, stomach, spiral intestine, hematopoietic tissue within the anterior kidney, and in the branchial septum and primary lamellae of the gills. Epicardial hyperplasia and granulomatous myocarditis were associated with the larvae. Although identification of the larvae was impossible due to lack of distinct morphological features, they resembled dracunculoid larvae previously reported from sharks.

No abstract

Dilated cardiomyopathy with ataxia (DCMA) syndrome is a rare mitochondrial disorder caused by mutations in the poorly understood DNAJC19 gene. The clinical presentation of DCMA is very diverse with symptoms ranging from mild cardiac dysfunction to intractable heart failure leading to death in early childhood. Although several lines of evidence indicate that DCMA symptoms are linked to mitochondrial function, the molecular underpinnings of this disease are unclear and there is no way to predict which patients are at risk for developing life-threatening symptoms. To address this we developed a metabolic flux assay for assessing the metabolic function of mitochondria in dermal fibroblasts derived from DCMA patients. Using this approach we discovered that fibroblasts from patients with DCMA showed elevated glutamine uptake, increased glutamate and ammonium secretion, and elevated lactate production when compared to controls. Moreover, the magnitude of these metabolic perturbations was closely correlated with patient cardiac dysfunction. This clinical/metabolic correlation was confirmed in a second blinded cohort of DCMA fibroblasts. Moreover, our metabolic flux diagnostic strategy correctly differentiated severe from mild DCMA cases with only one incorrect patient classification (positive predictive value 1.0 and negative predictive value 0.83). These findings suggest that glutamine catabolism is abnormal in DCMA and may serve as an early biomarker for predicting clinical progression.