Discussion

We describe a very unusual neonatal presentation of Barth syndrome with unique echocardiographic findings resulting from the deranged/altered haemodynamic status. Cardiac findings included severe cardiomyopathy including a combination of dilated, hypertrophic cardiomyopathy and left ventricle non-compaction. Echocardiographic findings mimicking tricuspid atresia or “pseudo tricuspid atresia” where the tricuspid valve leaflet did not move at all and there was obligatory right-to-left atrial shunt. Despite no tricuspid valve leaflet excursion and no forward flow in diastole, there was significant regurgitation across this atretic appearing tricuspid valve.

The possible mechanisms for no forward flow across the tricuspid valve and no valve leaflet excursion could be (1) a stiff and tense right ventricle with moderate hypertrophy and severely decreased systolic/diastolic function, (2) persistently elevated pulmonary resistance, or (3) ventricular interaction due to severe left and right ventricle dysfunction. In our case, as the pulmonary vascular resistance decreased with the use of inhaled nitric oxide and milrinone; and with the improvement of right ventricular systolic function, there was an improvement in the forward flow across the tricuspid valve. Prostaglandin was weaned off on day 4 of age to let the ductus arteriosus close spontaneously. However, though the ductus became smaller in size, ductus arteriosus continued to be patent until her death. Wald et al summarised the clinical course of 28 patients with neonatal Ebstein’s anomaly with anatomical and functional pulmonary valve obstruction. Amongst 24 patients who received prostaglandin, 17 patients discontinued prostaglandin after the relief of the pulmonary obstruction, which resulted in uneventful ductal constrictions. They concluded the early ductal closure in the absence of outflow tract obstruction and early limitation of ductal patency after relief of the obstruction may contribute to improved survival in neonates with Ebstein’s anomaly.^{Reference Wald, Adatia, Van Arsdell and Hornberger1}

On a detailed review of the literature, we found only one case reported by Patel and colleagues of functional tricuspid atresia in a neonate with cardiomyopathy who was diagnosed prenatally. This neonate had a normal initial foetal echocardiogram with a strong family history of cardiomyopathy and a follow-up echocardiogram at 30 weeks gestation showed functional tricuspid and pulmonary atresia with biventricular systolic dysfunction and left ventricle non-compaction. The echocardiographic findings were similar to our case, including the mixed type of cardiomyopathy and no forward flow across the tricuspid valve but regurgitation. This supports that a similar ha emodynamic derangement was playing a role for the lack of tricuspid valve leaflet excursion and forward flow resulting in “pseudo tricuspid atresia.” The baby was managed similarly with prostaglandin drip, inotropic, and ventilator support. The authors report improved antegrade tricuspid and pulmonary blood flow by 2 weeks of age and off prostaglandin by 3 weeks of age. In their case, the underlying cause of cardiomyopathy was CAP2 gene mutation, which is implicated in the regulation of actin dynamics, sarcomere organisation in striated muscles, and possibly cardiac conduction disorders.^{Reference Patel and Peterson2} Even though the clinical presentation was strikingly similar, our patient had a lethal outcome, unlike this patient. On molecular testing, our patient was found to have a mutation in the TAZ gene in the distal region of chromosome Xq28 as seen in Barth syndrome. This mutation affects the production of tafazzin, a protein located in mitochondria that alters cardiolipin, which plays a critical role in the mitochondrial inner membrane. This may affect adversely multiple systems in the body, especially those with high energy demands like the heart and skeletal muscles.^{Reference Sabbah3,Reference Dudek and Maack4} Clinical presentation can be highly variable, and cardiomyopathy is the major clinical feature especially dilated cardiomyopathy. The causes of neonatal cardiomyopathy include neonatal asphyxia, myocarditis, arrhythmia, neuromuscular diseases, and other genetic disorders. Identification of the exact cause is usually difficult, and possible in only one-third of the patients. Genetic form of dilated cardiomyopathy occurs in 25–50% of patients.^{Reference Soares, Rocha and Pissarra5} It is likely that neonatal asphyxia contributed to the clinical picture and to the severity and early presentation of cardiomyopathy in our patient.

Our case highlights an interesting haemodynamic phenomenon of “pseudo tricuspid atresia” seen echocardiographically in patients with significant haemodynamic derangement resulting from cardiomyopathy. Regurgitation may be the only “telltale sign” for the patency of the valve in this situation. As cardiac functioning improves, forward flow across the valve is established with judicious use of inotropes, afterload reducing agent, and or pulmonary vasodilator.