10- year-follow-up in patients with Long-Chain 3-Hydroxy Acyl CoA Dehydrogenase Deficiency (LCHADD) treated with heptanoate (C7)

Manuela Zlamy (1), Karin Pichler (1), Miriam Michel (1), Sabine Scholl-Bürgi (1), Daniela

Karall (1)

(1) Department of Pediatrics I, Inherited Metabolic Disorders ,Medical University of Innsbruck, Austria Corresponding author:

Manuela, Zlamy, MD PhD

Department of Pediatrics I, Inherited Metabolic Disorders Medical University of Innsbruck

Innsbruck, Austria

e-mail: manuela.zlamy@i-med.ac.at Phone: +0043 512 504 23600

Long-chain 3-hydroxy acyl CoA dehydrogenase deficiency (LCHADD) is an autosomal recessive disorder. In patients with LCHADD the accumulation of toxic intermediates of β- oxidation causes either  immediate symptoms likehypoketotic hypoglycaemia as well as long- term complications. Therapy with heptanoate (C7) utilizes the anaplerotic effect of this  substance, wherethe allocation of an odd-carbon numbered substrate for  the citric acid cycle and the electron transport chain enhances ATP production.

We retrospectively evaluated clinical and biochemical parameters of 3 patients treated with heptanoate and a fat-defined diet over a time period of almost 10 years. All patient have confirmed LCHADD and  are  homozygous for the common mutation c.1528G>C.

The treatment dose of heptanoate equates 0.6-0.8 g/kg/d. Patients treated with heptanoate appeared clinically more stable than before therapy. Hospitalization rates and days of hospitalisations decreased in all 3 patients after initialization of therapy. Patient 1 showed no more CK  peaks  after  heptanoate  was  started.  Patient  2  still showed episodes of rhabdomyolysis but the associated  CK  concentrations  were  lower  than  before. Patient 3 showed laboratory signs of hepatopathy during infections, without any significant changes of the CK concentrations.

Our data shows, that with ongoing age patients treated with heptanoate clinically stabilize. However,  it  is unclear if this stabilization is due to the anaplerotic effect of heptanoate or less infection rates with increasing age.

Furtherprospective placebo-controlled studies as well as development of in-vitro and in-vivo test models are needed to evaluate the exact impact of heptanoate supplementation and  to  clarify the cellular mechanisms in the use of heptanoate.

Reference: Karall D, et al. Clinical outcome, biochemical and therapeutic follow-up in 14 Austrian patients with Long-Chain 3-Hydroxy Acyl CoA Dehydrogenase Deficiency (LCHADD). Orphanet Journal of Rare Diseases. 2015; 10:21.

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