ADRENOLEUKODYSTROPHY, DIETARY SUPPORT THERAPY IS A FUNDAMENTAL HELP
The latest generation foods for medical purposes can penetrate the blood-brain barrier, acting on the central nervous system
“To date, early diagnosis and dietary support therapy are fundamental in the treatment of adrenoleukodystrophy”, explains Prof. Marco Cappa, Head of the Endocrinology Multispecialty Department at the Department of Paediatric Medicine of Rome’s Bambino Gesù Hospital. X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disease that forms part of the leukodystrophy family and has an estimated incidence of approximately once case per 20,000 births. It is a metabolic disease that affects not just the brain, the spinal cord and the peripheral nerves, but also the cortex of the adrenal glands and, at times, the testicles. The symptoms correlate to an anomalous accumulation of VLFCA (Very Long Chain Fatty Acids) in certain cells of the nerve tissue or in the adrenal gland.
“There is only one definitive cure for this disease: the replacement of the diseased gene with a healthy one”, points out Prof. Marco Cappa. “This is all done with gene therapy, which, however, is not always an option. If this approach is applied to patients who already suffer from alterations in the central nervous system, the risk of causing damage is higher than the possibility of benefits. That is why a ‘score’ has been developed, i.e. a scale for assessing the grade of neuroradiological compromise which makes it possible to select the patients who, as they present an early stage of deterioration, can undergo gene therapy or a marrow transplant. In all other cases, since adrenoleukodystrophy is a metabolic disease, support treatment consists mainly in dietary and anti-inflammatory therapy”.
X-ALD can appear at various ages and present clinical manifestations of various grades of severity:
– X-linked cerebral adrenoleukodystrophy (X-CALD). It is the most severe form and only appears during childhood. The initial signs of X-CALD are a moderate cognitive deficit, followed by reduction of visual acuity, central deafness, ataxia, and, sometimes, convulsions and dementia. It can lead the young patients to a neurovegetative state or death in a few years. Cerebral adrenoleukodystrophy in adults is identical to X-CALD that manifests during childhood, but it appears at a more advanced age.
– Adolescent X-linked adrenoleukodystrophy (X-ALD). It appears in adolescent males or in young male adults, accompanied by adrenal insufficiency (AI). With time, it often degenerates in adrenomyeloneuropathy (AMN).
– Adrenomyeloneuropathy (AMN). It appears later (average age: 30 years) and is characterised by slowly progressing symptoms that may include limb rigidity, weakness and pain in the hands and feet, spasms, urinary problems, and sexual dysfunction.
– Adrenoleukodystrophy with isolated adrenal insufficiency. It is sometimes confused with Addison’s disease (due to the accumulation of long and very long chain fatty acids in the adrenal gland) and manifests with tiredness, bronze colouring of the skin, nausea, weight loss, hypotension, and hypoglycaemia. Of these patients, 50% may, over time, also develop neurological symptoms.
– Adrenoleukodystrophy in women who carry X-ALD. It is characterised by less severe symptoms compared to male sufferers from the disease and it manifests later (after 40 years of age). In general, women present symptoms that are typical of adrenomyeloneuropathy. The cerebral or adrenal forms are rare (2% and 1%, respectively). “The disease is transmitted with the X chromosome”, explains Prof. Cappa. “Theoretically, therefore, women who carry it should have another X that compensates for the diseased one. In actual fact and due to a complex mechanism, known as “skewed X inactivation”, it is possible that the diseased X prevails over the healthy one and allows, partly, the disease to manifest. A study that we performed in 2019 shows how, after forty years of age, the incidence of this condition can even reach 70%”.
“In general – continues the Bambino Gesù expert – dietary support therapy is an important help for all types of adrenoleukodystrophy. Before all else, we prescribe a diet low in VLFCA, put together by a nutritionist. As a second step, we administer the foods known as “foods for special medical purposes”. The three medications that have mostly been used over time are: Lorenzo’s Oil, Adrenomix, and Aldixyl. They are oil mixes that can lower VLCFA levels. However, while the old Lorenzo’s Oil could reduce the levels of fatty acids in the blood but could not pass through the blood-brain barrier, new generation products, such as Aldixyl, can achieve that”.
“Specifically – continues Prof. Cappa – the composition of Aldixyl makes for a direct action on the central nervous system (CNS). In fact, this formulation, which uses glycerol trioleate and erucic acid, which are effective in the peripheral reduction of fatty acid levels, has been supplemented with conjugated linoleic acid (CLA) triglycerides, that allow the product to pass through the blood-brain barrier and to regulate VLCFA metabolism at the level of the central nervous system. Lastly, the presence of a mix of powerful anti-oxidants at high doses (alpha lipoic acid, reduced L-glutathione, and vitamin E) reinforces the anti-inflammatory action in the entire body”.
In fact, inflammationis the ‘motor’ of adrenoleukodystrophy. The accumulation of fatty acids in the central nervous system causes phlogosis and leads to the condition manifesting. “This is why it is crucially important to combine dietary therapy with a treatment with anti-inflammatories, such as N-acetylcysteine”, clarifies Prof. Cappa.
“This type of combined therapy must start as soon as possible, even in patients who are candidates for a marrow transplant”, underlines the expert. “This is fundamental in order to immediately reduce the accumulation of long chain fatty acids before the symptoms of the disease start manifesting. For this reason, in collaboration with the Italian Adrenoleukodystrophy Association NPO (AIALD), the Italian United Adrenoleukodystrophy Association (AILU), and ELA Italia ONLUS – European Association against Leukodystrophy, we are fighting to get approval in Italy of neonatal screening for adrenoleukodystrophy. In fact, given that the disease’s mechanism is caused by an increase in fatty acids, an early diagnosis and a prompt intervention could slow down the development of the condition or even check it. This is what we hope”.