ESPE Abstracts

Background: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a newly reported inborn error of metabolism caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). TRNT1 mutations cause a complex multisystem disease leading to manifestations in most organs. We here described the effect of growth hormone (GH) treatment on short stature in two siblings with TRNT1 deficiency.

Case presentation: The two siblings presented with developmental delay, anemia, elevated transaminases, recurrent infection, hearing loss, macrocephaly and severe failure to thrive. Both were initially diagnosed with SIFD (sideroblastic anemia, immunodeficiency, fever, developmental delay) and later confirmed to have TRNT1 mutation by whole exome sequencing. Patient 1 is 6 years old female who initially presented to endocrine clinic at age 18 months of age for severe short stature and episodes of hypoglycemia. Her lab evaluation was only remarkable for low IGFI. Other pituitary evaluation and hypoglycemia workup were unrevealing. She was started on GH treatment at 18 months of age. Her hypoglycemia resolved and growth velocity is also improving. As of now, she has been on GH treatment for 3 and half years. Her height SDS has increased from pretreat - 4.22 to current - 3.22. Patient 2 is the younger male sibling of patient 1. He has more severe phenotypes than patient 1’s. He presented to endocrine clinic at 14 months of age also for severe short stature evaluation. His lab evaluation revealed low IGF I without other pituitary deficiency. He was started on GH treatment at 15 months of age and tolerated well. Since age of 20 months, he has been ill due to recurrent infection and severe anemia. As a result, his GH has been on hold.

Literature review: TRNT1 mutations cause a spectrum of disease ranging from a childhood-onset complex disease with manifestations in most organs to an adult-onset isolated retinitis pigmentosa presentation. The severity of the signs and symptoms vary widely. The clinical manifestations in children can include cyclical, aseptic febrile episodes, sideroblastic anaemia, B lymphocyte immunodeficiency, retinitis pigmentosa, hepatosplenomegaly, exocrine pancreatic insufficiency and renal tubulopathy, sensorineural deafness, cerebellar atrophy, brittle hair, partial villous atrophy and nephrocalcinosis. About 20 cases have been reported in the literature so far.

Conclusion: This is the first report of growth hormone treatment on short stature in the patients with TRNT1 deficiency. So far, the result of patient 1 appears to be encouraging although more long term data are needed.