What is ALD
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder.
The disease is caused by mutations in the ABCD1 gene (located on the X chromosome) that encodes the peroxisomal membrane protein ALDP, which is involved in the transmembrane transport of very long chain fatty acids (VLCFA; C22).
A defect in ALDP results in elevated levels of VLCFA in plasma and tissues. The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to increasingly severe cerebral demyelination. Most heterozygous females will develop symptoms by the age of 60. In individual patients, the course of the disease remains unpredictable.
EPIDEMIOLOGY
X-ALD is the most common peroxisomal disease with an incidence of 1 in 17,000 newborns.
The introduction of neonatal screening could lead to an increase in the detected incidence of X-ALD.
GENETIC TRANSMISSION
The disease is linked to the X chromosome. Affected carrier mothers transmit the genetic disorder to 50% of their sons and daughters, causing them to acquire affected status. Male patients, on the other hand, transmit the mutation to all their daughters, who acquire the status of affected carriers, but never to a son. If a patient is diagnosed with X-ALD, screening and family counselling are recommended.
ROLE OF VLCFA (VERY LONG CHAIN FATTY ACIDS)
X-ALD is caused by mutations in the ABCD1 gene, which encodes a protein that transports very long chain fatty acids. The accumulation of these fatty acids can cause destabilisation of the myelin sheath and impair axonal function, eventually leading to demyelination. The excess of fatty acids also stimulates an overproduction of free radicals, causing oxidative damage to proteins.
DIAGNOSIS
Neonatal screening is now technically feasible. It is based on the measurement of lysophosphatidylcholine C26:0 (26:0-lyso-PC) in dried blood spots. This test leads to the identification of pre-symptomatic patients with X-ALD. The implementation of such screening is regulated individually by each country.
If X-ALD is suspected in a male with neurological symptoms or Addison’s disease, the finding of elevated VLCFA levels in plasma confirms the diagnosis. For women with X-ALD, the preferred diagnostic test is the mutation analysis of the ABCD1 gene, because 15% of women with X-ALD have normal levels of VLCFA in plasma. Family screening follows the same recommendations.
PHENOTYPES – MALE PATIENTS WITH X-ALD
Isolated Addison's disease
Adrenal insufficiency
Symptoms
- Fatigue
- Nausea
- Weight Loss
- Hypotension
- Hypoglycaemia
- Difficulties in writing and reading
Cerebral ALD (C-ALD)
Rapid progression and increase in severity
Symptoms
- Withdrawn behaviour
- Hyperactive behaviour
- Apraxia
- Astereognosis
- Hearing impairment
- Decreased visual acuity
- Hemiparesis or Tetraparesis
- Cerebellar ataxia
- Convulsions
Adrenomyeloneuropathy
Developed by almost all patients in adulthood
Symptoms
- Progressive spastic paraparesis
- Sensory ataxia
- Sphincter dysfunction
- Leg pain
- Impotence
PHENOTYPES - FEMALE PATIENTS WITH X-ALD
Women develop symptoms similar to AMN (Adrenomyeloneuropathy), although, as in many X-linked diseases, female carriers are assumed to remain asymptomatic.
Physical examination of a large group of female carriers attending family conferences in the US revealed that more than 50 per cent had some kind of abnormality on neurological examination. An increasing number of symptomatic heterozygous women have been identified as the first member of their family to be affected by X-ALD, and the true incidence of AMN in heterozygous women is about 65% by the age of 60.
The onset of neurological symptoms mainly occurs between the fourth and fifth decade and are very similar to those observed in adult males with AMN. Sensory ataxia, faecal incontinence and pain in the legs are, however, often more prominent in symptomatic women with AMN. Brain involvement and adrenocortical insufficiency are rare, 2% and 1%, respectively.
The importance of nutritional therapy
“In general, dietary support therapy is an important aid for all types of adrenoleukodystrophy.”
First of all, substances are prescribed to help lower plasma VLCFA levels. A low VLCFA diet, developed by a nutritionist, is then drawn up and prescribed.
‘This type of combination therapy should be started as early as possible, even in marrow transplant candidates,’ the expert* emphasises. ‘This is essential to reduce the accumulation of long-chain fatty acids before the symptoms of the disease even begin to appear.’
SOURCE: Adrenoleukodystrophy, dietary support therapy is a key aid https://www.osservatoriomalattierare.it/malattie-rare/adrenoleucodistrofia/16693-adrenoleucodistrofia-la-terapia-di-supporto-dietetico-e-un-ausilio-fondamentale (*) Professor Marco Cappa Endocrinoloy Complex Operative Unit (UOC) University-Hospital Paediatric Department Bambino Gesù Children's Hospital - Scientific Institute for Research, Hospitalisation and Health Care (Rome - Italy)
Aldixyl® metabolic treatment for ALD
Aldixyl® is a food for special medical purposes indicated for the treatment of patients suffering from adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). The daily inclusion of Aldixyl® in the diet of patients with ALD and AMN brings significant benefits to the patient’s clinical picture.
Its daily use is essential in combination with Aldixyl® OILife.
The unique formulation of Aldixyl® crosses the blood-brain barrier and makes it possible to:
- Lower plasma levels of VLCFA
- Lower VLCFA levels in the CNS (Central Nervous System)
- Increase peroxisomal beta-oxidation
- Reduce IL-6 in the FCS (Cerebro-Spinal Fluid)
- Prevent the propagation phase of the peroxidative process
- Prevent protein oxidation
GTO and GTE
Triglycerides of oleic acid and erucic acid in a 4:1 ratio
Alfaxyl®
Antioxidants in Pharmaelle’s patented blend
TGCLA
Triglycerides of Conjugated Linoleic Acid
Vitamin E
Powerful fat-soluble
antioxidant
How does Aldixyl®work?
The action of Aldixyl® is determined by its composition, which ensures the optimal balance between Oleic and Erucic acid, by the presence of Triglycerides of Conjugated Linoleic Acid (TGCLA), which are able to exert their fat metabolism regulating action directly on the nervous system, and finally by the presence of the unique blend of selected and powerful antioxidants, Alfaxyl® (alpha-lipoic acid) and Vitamin E.
Attention to product quality led to the choice of the amber bottle
The inviolability of Aldixyl® is ensured by the use of a dark bottle suitable for containing the product and preventing damage from sun exposure, with a cap that, thanks its ring nut, guarantees a perfect seal.
The bottle is placed in a package designed and developed to preserve the correct chemical, physical and organoleptic features of the mixture.
The case enclosing the bottle is designed to avoid exposure to light, which could trigger deterioration processes in the product. Moreover, the 300 ml format is the most suitable for a long shelf life.
Thanks to the technology used in product development and the care and controls also present in the packaging processes, the stability of Aldixyl® is guaranteed for at least 36 months from the date of production.
ALDIXYL
Aldixyl è un alimento destinato a fini medici speciali indicato per il trattamento di pazienti affetti da Adrenoleucodistrofìa (ALD) e Adrenomieloneuropatia (AMN).
Permette di:
- Abbassare i livelli VLCFA nel plasma e nel SNC (Sistema Nervoso Centrale)
- Incrementare la beta-ossidazione perossisomale
- Ridurre le IL-6 nel FCS (Fluido Cerebro-Spinale)
- Prevenire la fase di propagazione del processo perossidativo
- Prevenire l’ossidazione delle proteine
COME AGISCE
L’azione di Aldixyl…
… è determinata dalla sua composizione, che garantisce il bilancio ottimale fra acido Oleico e acido Erucico, dalla presenza dei Trigliceridi dell’acido Linoleico coniugato (TGCLA) che sono in grado di esercitare direttamente sul sistema nervoso la Ioro azione regolatrice del metabolismo dei grassi ed infine dalla presenza deII’esclusiva miscela di selezionati e potenti antiossidanti, Alfaxyl® (acido alfa-lipoico) e Vitamina E.
Dal punto di vista nutrizionale è necessario comunque ridurre l’apporto di alimenti contenenti acidi grassi a catena molto lunga (VLCFA). La messa a punto di diete a basso contenuto di VLCFA deve essere eseguita da un nutrizionista. Il processo produttivo ha reso possibile il perfezionamento della formula attraverso l’aggiunta di sostanze che permettono la riduzione degli stress ossidativi.
Questa innovativa associazione permette inoltre un netto miglioramento delle compliance del paziente.
L’aroma neutro e naturale del prodotto ne garantisce una migliore palatabilità.
La miscela GTO/GTE (esteri trigliceridi dei due composti) si ottiene attraverso un delicato processo di esterificazione e purificazione.
PACKAGING
L’inviolabilità di Aldixyl è assicurata dall‘utilizzo di un flacone scuro idoneo a contenere il prodotto e prevenire i danni dovuti all‘esposizione solare, dotato di tappo che, grazie alla ghiera in esso contenuta, garantisce una perfetta chiusura ermetica. Il flacone viene inserito in una confezione progettata e sviluppata per preservare la corretta conservazione delle caratteristiche chimico-fisiche ed organolettiche della miscela. L‘astuccio che racchiude il flacone ha Io scopo di evitare l’esposizione alla Iuce, la quale potrebbe innescare i processi di deterioramento del prodotto. Inoltre, il formato da 300 ml è il più adatto a garantire la migliore conservazione.
Grazie alla tecnologia utilizzata per Io sviluppo del prodotto, alla cura ed ai controlli presenti anche nei processi di packaging, la stabilità di Aldixyl è garantita per almeno 36 mesi dalla data di produzione.
Tipo
Alimento destinato a fini medici speciali
Capacità
300 ml
Aldixyl® OILife
ESSENTIAL AID TO METABOLIC THERAPY
Aldixyl® OILife, rich in oleic acid (long-chain triglyceride, LCT) is to be used as a fat replacement source as part of a fat-restricted diet.
For use in the dietary management of patients with ALD and AMN.
From a nutritional point of view, it is necessary to reduce the intake of foods containing very long chain fatty acids (VLCFA). ALDIXYL® OILife is a nutritional food with a specific formulation indicated for the dietary treatment of patients suffering from adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN).
The daily use of ALDIXYL® OILife in the diet of ALD and AMN patients, in combination with the use of Aldixyl®, makes it possible to reduce the intake of very long chain fatty acids (VLCFAs), the main cause of the neurodegenerative process of adrenoleukodystrophy and adrenomyeloneuropathy.
USE AND TASTE
Aldixyl® OILife, rich in pure oleic acid and flavoured with olive oil, can be used by patients who are following a low-fat diet/dietetic regime. Suitable for seasoning dishes and cooking, it comes in a dark 750 ml bottle that is also very practical at the table, for use during meals. The low VLCFA diets must be devised by a qualified dietician.
Classification
Food for special medical purposes – Seasoning oil
Bottle
750 ml
PRESCRIPTION PROCEDURE
Aldixyl® and Aldixyl® OiLife cannot be purchased without a doctor’s prescription.
In Italy, in order to obtain the treatment, the specialist doctor who made the diagnosis must draw up the treatment plan. Once the treatment plan has been obtained, depending on regional regulations, one can request metabolic treatment directly at the pharmacy by showing the referral from the specialist or general practitioner.
If you live outside Italy, contact your specialist doctor or patient association to find out how to obtain Aldixyl®.
Aldixyl® is produced and bottled regularly and is always available for direct delivery to pharmacies or local health authorities.
Doctors and pharmacists
To request more information, please write to the email address:
info@aldixylald.com
QUOTES
FAQ
Pursuant to Regulation (EU) 609/2013 (Art. 2.2.g), an FSMP is a food product expressly prepared or formulated and intended for the dietary management of patients, including infants, to be used under medical supervision; it is intended for the complete or partial feeding of patients with a limited, disturbed or impaired ability to take in, digest, absorb, metabolise or eliminate ordinary foodstuffs or certain nutrients contained therein or metabolites, or with other nutritional requirements determined by clinical conditions and whose dietary management cannot be achieved solely by modification of the normal diet.
Aldixyl® is a food for special medical purposes indicated for the treatment of patients suffering from adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). Its daily use is essential in combination with Aldixyl® OILife.
Visit the appropriate section of the website for more information
Visit the appropriate section of the website for more information
FOOD FOR SPECIAL MEDICAL PURPOSES (FSMP). TO BE USED ONLY UNDER MEDICAL SUPERVISION. ALWAYS REFER TO YOUR DOCTOR.
Consult your specialist doctor for information
FOOD FOR SPECIAL MEDICAL PURPOSES (FSMP). TO BE USED ONLY UNDER MEDICAL SUPERVISION. ALWAYS REFER TO YOUR DOCTOR.
For oral use only. Aldixyl® can be consumed in a single intake, or divided into several daily doses. It may be useful to supplement the diet with essential fatty acids.
Consult your specialist doctor for information
FOOD FOR SPECIAL MEDICAL PURPOSES (FSMP). TO BE USED ONLY UNDER MEDICAL SUPERVISION. ALWAYS REFER TO YOUR DOCTOR.
Adults and children: take Aldixyl® according to your doctor’s instructions, using the handy dosage dispenser on the bottle cap.
Aldixyl® is to be used under medical supervision. For oral use only, it should not be administered parenterally. It cannot be used as a sole source of nutrition. Do not inject or administer in any other way. Always take Aldixyl® in accordance with your doctor’s instructions. If in doubt, always consult your doctor.
If you take more Aldixyl® than you should or if you accidentally ingest an excessive dose of Aldixyl® consult your doctor, although there is no risk of overdose.
Consult your doctor for information on possible interactions with other drugs.
Consult your specialist doctor for information
When the product is still sealed and unopened, store it in a cool and dry place, protected from light, in its own packaging. After opening, store preferably in the refrigerator, taking care to bring to room temperature before administering. Carefully close the bottle after use. Once opened, consume within a month.
Aldixyl® MUST ONLY BE TAKEN ON PRESCRIPTION FROM A SPECIALIST.
Aldixyl® OILife is an essential aid to metabolic therapy in combination with the use of Aldixyl®.
Visit the appropriate section of the website for more information
Source overview of pathology:
X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management Marc Engelen1,3*, Stephan Kemp2,3, Marianne de Visser1, Björn M van Geel1,4, Ronald JA Wanders2, Patrick Aubourg5,6 and Bwee Tien Poll-The1,3
© 2012 Engelen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.