FATAL CONGENITAL MYOPATHY AND GASTROINTESTINAL PSEUDO-OBSTRUCTION DUE TO POLG1 MUTATIONS

Abstract

Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase γ ( POLG1 ) are associated with a range of clinical syndromes characterized by secondary mtDNA defects, including mtDNA depletion and multiple mtDNA deletions.1 The phenotypic spectrum of POLG1 -associated disease ranges from fatal childhood encephalopathy with intractable epilepsy and liver failure (Alpers-Huttenlocher syndrome)2 to late-onset clinical disease affecting a single organ (for a review, see reference 3). We describe a fatal skeletal and visceral myopathy in the neonatal period associated with recessive POLG1 mutations. ### Case report. A newborn boy of healthy nonconsanguineous parents was delivered at 37 weeks’ gestation by cesarean section. His mother (primipara, 32 years old) had been admitted to our hospital 2 weeks previously because of reduced fetal intrauterine movements and polyhydramnios. The child’s birthweight was 2,330 g (<10th percentile), length 47 cm, and head circumference 33.2 cm (25th percentile). He had low-set ears and bilateral clubfoot. Apgar scores were 2, 6, and 7 at 1, 5, and 10 minutes. The child presented with severe hypotonia and generalized muscle weakness, requiring ventilatory assistance and total parenteral nutrition. Weaning failed because of inadequate pulmonary ventilation and respiratory acidosis. Hearing loss was detected by auditory evoked potentials, while cranial MRI showed mildly enlarged ventricles and liquor spaces. Two days …