VERY LOW FAT DIET WITH SUPPLEMENTATION OF HIGH GTO: GTE RATIO OIL IN THE DIETARY MANAGEMENT OF PATIENTS WITH ADRENOLEUKODYSTROPHY

Backgroud Adrenoleukodystrophy is a severe progressive genetic disease that predominantly affects adrenal glands, spinal cord and myelin of the nervous system.1 It is an X-linked disease affecting the ABCD1 gene located on X chromosome long arm: Xq28. More than 940 pathological variants of this gene exist. The ABCD1 gene encodes for the ABCD1 protein, a peroxisomal transporter with high specificity for VLCFAs (very long-chain fatty acids; ≥C20)2. Adrenoleukodystrophy is characterized by inability of cells to metabolize/degrade VLCFAs, leading to accumulation in particular in the brain, spinal cord, testis, and adrenal glands3. VLCFAs are normally present 65 as constituents of brain membranes and myelin. They are also present in different food sources (oils, milk, dairy products, bran, fruits, vegetables) and are produced by elongation of shorter fatty acids. The accumulation of VLCFAs induces depolarization of mitochondria, deregulation of intracellular calcium homeostasis, causing oxidative damage and inducing microglia apoptosis4. CASE 1A 61-year-old patient was referred to our clinic for nutritional status evaluation for overweight and adrenomyeloneuropathy (AMN) with adrenal insufficiency (2018) management. The onset of clinical symptomatology (2003) was characterized by motor impairment, with subsequent spastic lower limb paraparesis (2010), and ataxic gait. The dietary history reveals an inadequate energy and nutrient intake compared to daily requirements according to the indications for his current pathology. The patient reported poor adherence to the dietary prescription. The Physical Activity Level was estimated as 1.45 (sedentary behaviour) according to LARN 2014 (Reference intake levels of nutrients and energy for the Italian population). The following data were collected: Anthropometry: body weight (BW): 84kg, height: 171cm, BMI (Body Mass Index): 28,7 kg/m2; Waist circumference: 98cm. Mid-arm circumference: 32cm. Calf circumference: 83cm. DXA: FM (Fat mass) 22kg (26% of BW); LBM (lean body mass) 62,6kg (74% of BW); left femoral neck BMD (Bone Mineral Density) T-score -1,2 (osteopenia); lumbar spine BMD T-score +1,5. Handgrip strength: right arm (right-handed sbj) mean: 16kg, left arm mean 16kg. Sit-to-stand test: not performed due to patient motor difficulties. SPPB (Short Physical Performance Battery) score: 2/12MNA (Mini Nutritional Assessment) score: 22/30 (at risk of malnutrition) Altered Blood Tests: Total cholesterol 235.8mg/dl (r.v. 1-235.5mg/dl), LDL 155.7mg/dl (r.v.. 100-129 mg/dl), Hb 13g/dl (r.v.. 13.5-16.5g/dl), Folate 3.6ng/mL (r.v.. 3.8-16.0), Activated protein C resistance Funct. 140% (r.v.. 64-128), PT 9.72sec (r.v. 11.0-16.0), Factor V 187% (r.v. 62-150), Factor VII 121% (r.v. 70-120). CASE 2A 60-years-old patient with diagnosis of AMN (April 2022), adrenal insufficiency (July 2022), and insulin resistance (2023) was referred to our clinic for nutritional evaluation. Dietary history revealed an inadequate energy and nutrient intake based on daily requirements and indications for his current disease. Based on the 24-hour dietary recall the patient reported reduced frequency of 66 VI Congress SINuC (Società Italiana di Nutrizione Clinica e Metabolismo) frontiersin.org pulse consumption and excessive consumption of foods high in saturated fats and processed foods compared to Mediterranean dietary pattern. The Physical Activity Level was estimated as 1.51 according to LARN 2014. The following data were collected: Anthropometry: BW 71.2kg, height 170cm, BMI: 24.6 kg/m; Waist circumference: 99cm. Left Arm Circumference: 30cm. Left calf circumference 38.5cmDXA: FM 17.5kg (22.1% of BW). FFM 59,6kg (79,9% of BW). ALM/W (Appendicular Lean Mass/Weight): 37.6%(n.r. > 28.27%); left femoral neck BMD T-score -0.3; lumbar spine BMD T-score -1.5 (osteopenia). Handgrip strength: right arm (right-handed sbj): 48.7kg; left arm: 43.4kg. Sit-to-stand test: 10.41sec (score 4/4). SPPB score: 12/12. MNA score: 28/30 (normal nutritional status). Altered Blood Tests: Lipase 61 U/L (n.r. 13-60U/L), ALT 74 U/L (n.r. 10-40U/L.), Direct Bilirubin 0.43mg/ dl (n.r. <20mg/dl), Total cholesterol 261.7mg/dl (n.r. 81-235.5mg/dl), LDL 174.5mg/dl (n.r. b 100-129mg/dl), Urate 7.56mg/dl (n.r. 3.36-7.22mg/dl), Ferritin 545μg/l (n.r. 30-400μg/dl), Activated protein C resistance Funct. 150% (n.r.64-128%), PT 10.23sec (n.r. 11.0-16.0sec), factor VII 155% (n.r. 70-120%), free protein S 135% (n.r. 58-128%). MANAGMENT For both patients dietetic therapy was prescribed considering a fat intake from foods equal to 10% of energy intake + 20% fat intake from Aldixyl® and Aldixyl OiLife®, with 5-10 g/day of C26:0. Finally, the dietetic prescription, considering the respective metabolic nutritional requirements, provided 1700 total kcal/day, including carbohydrates 276g, fats 19g, proteins 106 g, Aldixyl®25mg/day for case 1 and 40mg/day for case 2, Aldixyl OiLife®20ml/day for case 1 and 30ml/day for case 2. Both patients received nutritional advice to minimize dietary intake of VLCFAs: to consume fruits and vegetables without peel or seeds, to avoid vegetable oils and nuts, to avoid processed foods, whole grains, and whole or semi-skimmed milk and dairy products, to prefer skimmed milk and dairy products, and to avoid egg yolk. The following laboratory and instrumental investigations were requested to complete the diagnostic procedure: - Circulating VLCFAs lipid profile - Circulating Vitamin A, E, K - PDFF (Proton Density Fat Fraction) bone marrow adipose tissue67 Conclusion There is no curative treatment for adrenoleukodystrophy. To improve nutritional status and to reduce the clinical impact of the disease, it is necessary to pay attention on appropriate nutritional metabolic requirements by ensuring the correct intake of micro- and macronutrients, in particular fat-soluble vitamins (A,D,K,E) and lipids. The therapeutic focus is a lipid intake of 10% through the diet + 20% with Aldixyl®and Aldixyl Oilife®, minimizing dietary intake of VLCFAs7 and not exceeding 5-10g/day of C26:0. Dietary advices and nutritional counselling are an essential part of the nutritional approach to improve the adherence to dietary prescription and, therefore, to minimize, the risk of malnutrition and complications of adrenoleukodystrophy. References [1] Di Biase A, Avellino C, Salvati S. Adrenoleucodistrofia: genetica, fenotipi, patogenesi e trattamento [Adrenoleukodystrophy: genetics, phenotypes, pathogenesis, and treatment]. Ann Ist Super Sanita. 1999;35(2):185-92. Italian. PMID:10645651. [2] https://adrenoleukodystrophy.info [3] Singh I, Moser HW, Moser AB, Kishimoto Y. Adrenoleukodystrophy: impaired oxidation of long chain fatty acids in cultured skin fibroblasts an adrenal cortex. Biochem Biophys Res Commun. 1981 Oct 30;102(4):1223-9. doi: 10.1016/s0006-291x(81)80142-8. PMID:6797420.68 VI Congress SINuC (Società Italiana di Nutrizione Clinica e Metabolismo) frontiersin.org [4] Whitcomb RW, Linehan WM, Knazek RA. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Invest. 1988 Jan;81(1):185-8. doi:10.1172/JCI113292. PMID:2891726; PMCID:PMC442491. [5] Van Duyn MA, Moser AE, Brown FR 3rd, Sacktor N, Liu A, Moser HW. The design of a diet restricted in saturated very long-chain fatty acids: therapeutic application in adrenoleukodystrophy. Am J Clin Nutr. 1984 Aug;40(2):277-84.doi:10.1093/ajcn/40.2.277. PMID:6465061. [6] https://www.osservatoriomalattierare.it/malattie-rare/ adrenoleucodistrofia [7] Moser, Hugo W., and Janet Borel. “Dietary management of X-linked adrenoleukodystrophy.” Annual review of nutrition 15.1(1995):379-397.