# Anaplerotic Therapy Using Triheptanoin in Two Brothers Suffering from Aconitase 2 Deficiency

## TL;DR

Two brothers with a rare mitochondrial disease showed improved motor abilities after treatment with triheptanoin, which helps bypass a defective enzyme in their energy metabolism.

## Contribution

Demonstrates successful anaplerotic therapy using triheptanoin in patients with ACO2 deficiency.

## Key findings

- Triheptanoin improved motor abilities in two brothers with ACO2 deficiency.
- Homozygous deletion in the ACO2 gene was confirmed in the patients.
- Treatment bypassed defective aconitase 2 and supported citric acid cycle function.

## Abstract

Citric acid cycle deficiencies are extremely rare due to their central role in energy metabolism. The ACO2 gene encodes the mitochondrial isoform of aconitase (aconitase 2), the second enzyme of the citric acid cycle. Approximately 100 patients with aconitase 2 deficiency have been reported with a variety of symptoms, including intellectual disability, hypotonia, optic nerve atrophy, cortical atrophy, cerebellar atrophy, and seizures. In this study, a homozygous deletion in the ACO2 gene in two brothers with reduced aconitase 2 activity in fibroblasts has been described with symptoms including truncal hypotonia, optic atrophy, hyperopia, astigmatism, and cerebellar atrophy. In an in vivo trial, triheptanoin was used to bypass the defective aconitase 2 and fill up the citric acid cycle. Motor abilities in both patients improved.