Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo'soil"

Objectives-X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder o f peroxisomal fatty acid oxidation, biochemically characterised by the accu mulation of saturated very long chain fatty acids (VLCFAs), particularly he xacosanoic acid (C26:0). Dietary treatment with a 4:1 mixture of glyceroltr ioleate and glyceroltrierucate ("Lorenzo's oil") normalises plasma VLCFA co ncentrations, but neither ameliorates nor arrests the rapid progression of neurological symptoms in the cerebral variants of X-ALD. The efficacy of "L orenzo's oil" in the milder phenotypes of X-ALD was assessed, as this has b een much less investigated. Methods-Twenty two patients who were treated with "Lorenzo's oil" for at le ast 12 months for a median period of 2.5 (range 1.0-6.0) years were studied . Two had asymptomatic ALD, four the "Addison only" variant, 13 adrenomyelo neuropathy (AMN), and three were symptomatic female carriers. Results-The plasma C26:0 concentration normalised or near normalised in 19 patients (86%), in the three others it decreased significantly. Nevertheles s, disability as measured with the extended disability status scale score i ncreased mildly (0.5 (95% confidence interval (95% CI) 0.25-1.0)) in the 16 patients with neurological symptoms. Furthermore, one "Addison only" patie nt and one patient with AMN developed cerebral demyelination, and another " Addison only" patient developed AMN. Adrenocortical insufficiency evolved i n one patient with AMN, and hypogonadism in one patient with asymptomatic A LD and two patients with AMN. Nerve conduction, evoked potential studies (S EP, BAEP, VEP), and abnormalities on cerebral MRI did not improve. On the o ther hand, side effects were often noted-namely, mild increases in liver en zymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). We also found a mild decrease in haemoglobin concentrati on and leucocyte count. Conclusions-The data suggest that treatment with "Lorenzo's oil" neither im proved neurological or endocrine function nor arrested progression of the d isease. Furthermore, the oil often induced adverse effects. Therefore, it i s advocated that "Lorenzo's oil" should not be prescribed routinely to pati ents with X-ALD who already have neurological deficits.