3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency and Hyperinsulinemic Hypoglycemia: Characterization of a Novel Mutation and Severe Dietary Protein Sensitivity

• DOI: 10.1210/jc.2009-0423
• Publication Date: 2009-05-06T02:34:11Z
• Authors: Ritika R. Kapoor; Chela James; Sarah E. Flanagan; Sian Ellard; Simon Eaton; Khalid Hussain
• Keywords: Hyperinsulinemic hypoglycemia

HADH encodes for the enzyme 3-hydroxyacyl-coenzyme A dehydrogenase (HADH) and catalyses penultimate reaction in beta-oxidation of fatty acids. All previously reported patients with mutations gene hyperinsulinemic hypoglycemia (HH) showed raised plasma hydroxybutyrylcarnitine urinary 3-hydroxyglutarate.The aims study were: 1) to report a novel mutation not associated abnormal acylcarnitine or organic acid profile; 2) observation severe protein-sensitive HH three mutations.The index case presented at 4 months age hypoglycemic seizures. Her responded diazoxide, but she continued have episodes even on especially when consuming high-protein foods.Investigations confirmed (blood glucose level 1.8 mmol/liter simultaneous serum insulin 58 mU/liter) normal acylcarnitines urine Sequencing identified homozygous missense (c.562A>G; p.Met188Val). Hydroxyacyl-coenzyme activity was significantly decreased compared controls (index patient, mean +/- sem, 26.8 4.8 mU/mg protein; controls, 48.0 8.1 P = 0.029) skin fibroblasts. This patient severely protein sensitive. Two other children due also demonstrated marked sensitivity.Mutations are protein-induced HH, may