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A5626 - Multiple Mitochondrial Dysfunctions Syndrome Type 1: A Rare Cause of Pulmonary Hypertension in Infancy
Author Block: N. Villafranco1, A. Birjiniuk2, N. P. Varghese3; 1Pediatric Pulmonary, Baylor College of Medicine, Houston, TX, United States, 2Pediatrics, Baylor College of Medicine, Houston, TX, United States, 3Dept of Pulmonary Medicine, Baylor Coll of Med/Texas Childrens Hosp, Houston, TX, United States.
Intro: Pulmonary hypertension (PH) in infancy is most often seen as secondary to congenital heart disease and premature lung disease. It is rarely described in infants who have no history of these conditions, making up less than 1% of current registry data. We present a case of PH presenting in early infancy secondary to an inherited mitochondrial disorder.
Case: A 3-month-old female infant presented to the emergency department with irritability, poor feeding for 1-2 months, and weight loss. Family history was significant for a brother who died suddenly at 5 months of age from a “heart condition” after having a similar progression of worsening feeding and failure to thrive. The infant had an EKG done on presentation due to her brother’s history and it was notable for right ventricular hypertrophy. Follow up echocardiogram was consistent with severe PH with septal flattening and bowing during systole, right ventricular hypertrophy and dilation and right atrial dilation, estimating systemic to suprasystemic pulmonary pressures. She was admitted for nutritional management and right heart catheterization. Due to the family history, genetic studies were done which revealed 2 mutations of the NFU-1 gene consistent with the diagnosis of Multiple Mitochondrial Dysfunctions Syndrome Type 1 (MMDS1). Clinical deterioration, worsening echo findings and concern for tolerance of anesthesia prompted cancellation of cardiac catheterization and empiric therapy with sildenafil and bosentan. For her mitochondrial disease, she was started on ketogenic diet and vitamin B1 supplementation. The patient is now 6 months old, has developmental regression and continued poor feeding. Her echo remains severe but unchanged on dual therapy and she is hemodynamically stable on room air.
Discussion:MMDS1 is an autosomal recessive disease characterized by NFU-1 mutation. The NFU-1 gene is involved in the assembly of iron sulfur clusters within the mitochondrial respiratory chain. To date, fewer than 30 cases of this disease have been reported worldwide. It is associated with PH but this is not typically the presenting feature of this disease. Other characteristic features of this disease include lactic acidosis, failure to thrive, progressive encephalopathy, and death before age 2. The mechanism of PH in mitochondrial disease is still under investigation, however current theories include suppressed glucose oxidation leading to suppressed apoptosis, increased cell proliferation, and mitochondrial induced inflammasomes. Trial of therapy with sildenafil, bosentan has not been described in this disease. To date, the child appears to be tolerating therapy well and echocardiogram remains stable.