Persistent pulmonary arterial hypertension in the newborn (PPHN): A frequent manifestation of TMEM70 defective patients

Michela Catteruccia, Daniela Verrigni, Diego Martinelli, Alessandra Torraco, Teresa Agovino, Luisa Bonafé, Adele D'Amico, Maria Alice Donati, Rachele Adorisio, Filippo Maria Santorelli, Rosalba Carrozzo, Enrico Bertini, Carlo Dionisi-Vici

Research output: Contribution to journalArticlepeer-review


Introduction: Mutations in the TMEM70 are the most common cause of nuclear ATP synthase deficiency resulting in a distinctive phenotype characterized by severe neonatal hypotonia, hypertrophic cardiomyopathy (HCMP), facial dysmorphism, severe lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria (3-MGA). Methods and results: We collected 9 patients with genetically confirmed TMEM70 defect from 8 different families. Six were homozygous for the c.317-2A>G mutation, 2 were compound heterozygous for mutations c.317-2A>G and c.628A>C and 1 was homozygous for the novel c.701A>C mutation. Generalized hypotonia, lactic acidosis, hyperammonemia and 3-MGA were present in all since birth. Five patients presented acute respiratory distress at birth requiring intubation and ventilatory support. HCMP was detected in 5 newborns and appeared a few months later in 3 additional children. Five patients showed a severe and persistent neonatal pulmonary hypertension (PPHN) requiring Nitric Oxide (NO) and/or sildenafil administration combined in 2 cases with high-frequency oscillatory (HFO) ventilation. In 3 of these patients, echocardiography detected signs of HCMP at birth. Conclusions: PPHN is a life-threatening poorly understood condition with bad prognosis if untreated. Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient. This report further expands the clinical and genetic spectrum of the syndrome indicating PPHN as a frequent and life-threatening complication regardless of the type of mutation. Moreover, in these children PPHN appears even in the absence of an overt cardiomyopathy, thus representing an early sign and a clue for diagnosis.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number3
Publication statusPublished - Mar 2014


  • Mitochondrial diseases
  • Persistent pulmonary neonatal hypertension
  • TMEM70 defect

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Fingerprint Dive into the research topics of 'Persistent pulmonary arterial hypertension in the newborn (PPHN): A frequent manifestation of TMEM70 defective patients'. Together they form a unique fingerprint.

Cite this