ESPE Abstracts

Context: Mitochondrial encefalo-cardio-myopathy due to TMEM70 mutation is a very rare disease with frequent neonatal onset accompanied by laptic acidosis, hyperammonemia and 3-methylglutaconic aciduria.

Case presentation: Patient DT presented at 7.5 years due to short stature (height -3.11 SDS, MPH -1.09 SDS; weight -4.41 SDS), in the context of a complex syndromic picture characterized by intrauterine growth retardation, oligohydramnios, prenatal onset microcephaly; dysmorphism (carinated chest, irregular palmar folds, long poorly designed filter, thin vermilion, wide nostrils, thick and arched eyebrows, operated umbilical hernia, camptodactyly, congenital clubfoot), neurologic and neuromuscular involvement (mild mental retardation with mixed specific learning disorder-mixed type; chronic peripheral sensory neuropathy, with myoclonia, mild hypotonus and ligamentous laxity, vermian hypoplasia Dandy Walker like), cardiac involvement (repaired interatrial septal defect, aortic arch dilation, interventricular septum thickening, Wolff-Parkinson-White syndrome), audiological involvement (mean bilateral hearing impairment for acute frequencies). At the age of 14, DT was hospitalized for metabolic coma during a viral gastroenteritis with finding of metabolic acidosis, hyperlactacidemia, hyperammonemia with subsequent diagnosis of a mitochondrial disease (homozygous pathogenetic variant in the TMEM70 gene associated with type 2 ATP synthase deficiency inherited in an autosomal recessive manner) for which he started integration with iron, thiamine, carnitine, riboflavin. Since the age of 8, DT started growth hormone (GH) treatment due to a partial growth hormone deficiency (Peak-stimulated GH: 9.76 mg/l and 4.65 mg/l, n.v. >10 mg/l, IGF1: 54 ng/ml, n.v. 64-345 ng/ml); MRI showed a normal hypothalamic-pituitary region. The remaining pituitary tropins were always normal; puberty was regular in its onset and course. GH therapy was well tolerated and effective. At the last visit (16 years), height was 163 cm (-1.46 SDS), weight 44.3 kg (-2.49 SDS), Tanner stage P4G4, testicular volume 15 ml.

Discussion: Endocrine dysfunction is often observed in genetic mitochondrial diseases, including growth hormone insufficiency. According to the literature, faltering growth is present in 94% of surviving children with TMEM70 deficiency and short stature in 89%, while hypospadia and/or cryptorchidism are present in 50% of males. To the best of our knowledge, growth hormone deficiency and good response to GH treatment in these patients have not been reported so far.