Dietary therapy for a patient affected with 3-hydroxy-3-methylglutaric aciduria

Abstract

3-Hydroxy-3-methylglutaric aciduria (OMIM 246450) is an extremely rare genetic metabolic disorder of leucine caused by deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase). Affected patients present with life-threatening metabolic acidosis, hyperammonemia, and nonketotic hypoglycemia. Optimal outcome for patients depends on early diagnosis and treatment, prompt management of acute metabolic decompensation during the chronic stage, and long-term interprofessional health care programs. Nutritionists play a pivotal role in the care of metabolic disorders throughout the rest of a patient’s life. A 4-year-old intubated Bunun tribe female patient was admitted to the pediatric intensive care unit of the Buddhist Tzu Chi General Hospital (Hualien, Taiwan) due to status epilepticus, hypoglycemia, and severe metabolic acidosis. Results of urine gas chromatography with mass spectrometry revealed markedly elevated 3-methylglutaric acid, 3-hydroxy-3-methylglutaryl-CoA, and 3-hydroxyisovaleric acid, a finding consistent with a diagnosis of HMG-CoA lyase deficiency. She received an interdisciplinary health care program after acute management. Dietary therapy was the major part of the transdisciplinary health delivery process. Total daily calories were increased from 1400 kcal/day (targeted 60e80%) to 2100e2200 kcal/day (targeted 100%). The ratio of protein lipid and carbohydrate was 13%:24%:63% as recommended for healthy children. Lifelong protein restriction was essential. Total daily protein was given at a dose of 1.5e2 g/kg/day (target: above 50 g/day after the age of 4 years) and was administered at different growth and developmental stages. The daily leucine dose was 1000 mg (suggested dose ¼ 700e900 mg/day), 1.5% of the total protein amount was designed for her. Because leucine is an essential amino acid, close monitoring of optimal serum levels through blood sampling should be reached for better growth and development. Food avoidance was a major focus on restriction of protein from milk, meat, cheese, fish, poultry (including egg), beans, and nutlets, and even any foods containing milk and egg. Partial limited foods included sprouts (alfalfa, clover), radish, red bean, and murgbean. Unlimited fruits included vegetables and low protein starch such as green bean noodles, rice flour, pearl sago, lotus root powder, cornstarch, and corn flour, and low leucine foods such as potato powder were advised. The patient’s major protein source was from a special formula (I-Valex I and II; Abbott, Chicago, USA). Other nutrients such as multivitamins and minerals were prescribed. Daily oral L-carnitine was also prescribed to increase excretion of organic acid. The ability to recognize food labeling was taught to the parents, the patient, and school nurses. Servings for daily dietary content (Table 1) and sample meal plans were designed (Table 2).