“Idiopathic” pulmonary arterial hypertension in early infancy: Excluding NFU1 deficiency

Abstract

NFU1 deficiency is a rare metabolic disorder affecting iron–sulfur cluster synthesis, an essential pathway for lipoic acid-dependent enzymatic activities and mitochondrial respiratory chain complexes. It is a little-known cause of pulmonary arterial hypertension (PAH), while PAH is a prominent feature of the disease. We herein report on a female infant diagnosed as having idiopathic PAH since 1 month of age, who did not respond to bosentan plus sildenafil. NFU1 deficiency was only suggested and confirmed at 10 months of age when she demonstrated neurological deterioration along with high glycine levels in body fluids. Unexplained PAH in early infancy should prompt clinicians to perform amino acid chromatography searching for high glycine levels. Early recognition will avoid further invasive procedures and enable appropriate genetic counseling to be offered. No effective treatment is currently able to prevent the fatal course of this metabolic condition.

Efficacy of Beraprost Sodium Combined with Sildenafil and Its Effects on Vascular Endothelial Function and Inflammation in Patients Experiencing Left Heart Failure Complicated with Pulmonary Arterial Hypertension

“…As a 5-phosphodiesterase inhibitor [ 16 ], sildenafil can effectively inactivate 5-phosphodiesterase to raise the level of cyclic guanosine monophosphate in the body [ 17 ], and selectively act on the pulmonary vascular smooth muscle to effectively dilate pulmonary vessels [ 18 ], so it is combined with beraprost sodium to treat left heart failure complicated with pulmonary arterial hypertension. Since lung tissues are rich in 5-phosphodiesterases, after oral administration, sildenafil has a long half-life, long duration of action, and high specificity and causes few adverse reactions.…”

The effects of lipoic acid on respiratory diseases

“…Several clinical cases and animal experiments have demonstrated that deficiency in the mitochondrial iron-sulfur scaffold protein NFU1 may lead to pulmonary hypertension. In humans with idiopathic pulmonary hypertension, the impaired activity of lipoic acid synthesis due to defective NFU1 function may be associated with the occurrence of pulmonary hypertension [200] , [201] , [202] . In animal models, the NFU1 mutation resulting in lipoic acid synthase (LAS) deficiency was associated with PH [203] .…”

Comparison of the Effectiveness of Bosentan and Sildenafil in the Management of Persistent Pulmonary Arterial Hypertension in Neonates

“…Additional typical medications for PPHN include inotropes including intravenous dopamine, dobutamine, epinephrine, as well as norepinephrine. Dopamine raises the systemic blood pressure and seems to have adrenergic consequences (10) . Dobutamine enhances cardiac contractility while decreasing left ventricular capacity.…”