The long chain fatty acid buildup causes damage to the myelin sheath of the neurons of the brain, resulting in seizures and hyperactivity.

The other forms of ALD vary in timing of onset and in clinical severity, ranging from adrenal insufficiency alone to progressive paraparesis in early adulthood.

For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course.

[1] Initial symptoms in boys affected with the childhood cerebral form of ALD include emotional instability, hyperactivity and disruptive behavior at school.

[1] The incidence of new mutations in ALD (those occurring spontaneously, rather than being inherited from a carrier parent) is estimated at 4.1%, with the possibility that these are due to germline mosaicism.

[1] The lack of Coenzyme A does not permit the disintegration of the VLCFA, accumulating the same in the white matter, adrenal glands, and the testes more specifically in the Leydig cells not allowing the proper function of these organs.

Successful treatment of the demyelination process that affects the brain with either stem cell transplant or gene therapy does not immediately normalize the VLCFA levels in body tissues.

[4] When ALD is suspected based on clinical symptoms, the initial testing usually includes plasma very long chain fatty acid (VLCFA) determination using gas chromatography-mass spectrometry.

[3] Because the characteristic elevations associated with ALD are present at birth, well before any symptoms are apparent, there have been methods developed[9][10] in the interests of including it in newborn screening programs.

The accepted treatment for affected boys presenting with the cerebral childhood form of the disease is a bone marrow transplant, a procedure which carries significant risks.

[12] Initial attempts at dietary therapy in ALD involved restricting the intake of very-long chain fatty acids (VLCFA).

The parents of Lorenzo Odone, a boy with ALD, spearheaded efforts to develop a dietary treatment to slow the progression of the disease.

[2][7] Supplementation with Lorenzo's oil has been found to normalize the VLCFA concentrations in the body, although its effectiveness at treating the cerebral manifestations of the disease is still controversial and unproven.

CLA, through the activation of peroxisome beta oxidation, increases the catabolism of pro-inflammatory molecules and ROS, acting as an anti-inflammatory and antioxidant.

A group of Italian researchers of the Bambino Gesù Pediatric Hospital in Rome showed that the administration of Adrenomix (GTO, GTE and CLA), in addition to decreasing levels of VLCFA throughout the body, reduces neuro inflammation and improves somatosensory evoked potential, found unchanged or worsened with only administration of GTO and GTE.

Researchers at the IDIBELL- Hospital Duran i Reynals in Barcelona have shown that the early administration of a cocktail of powerful antioxidants, able to overcome the blood-brain barrier and thus carry out its activity at the CNS level, prevents the oxidative stress typical of the disease, intervenes on the initial axonal dysfunctions and therefore on locomotor damage.

In particular, CLA, in addition to overcoming the blood-brain barrier and regulating at the CNS level the metabolism of VLCFA is able to influence the catabolism of pro-inflammatory eicosanoids and lipid peroxidation products.

[22] While dietary therapy has been shown to be effective to normalize the very-long chain fatty acid concentrations in the plasma of individuals with ALD, allogeneic hematopoietic stem cell transplants is the only treatment that can stop demyelination that is the hallmark of the cerebral forms of the disease.

[24][25][26][27] There are also reports of hematologic cancer development in patients receiving this gene therapy, including myelodysplastic syndrome and acute myeloid leukemia.

It's not understood how they can have an ABCD1 gene variant and possess elevated VLCFAs and not exhibit either Cerebral ALD, Adrenal Insufficiency, or Adrenomyeloneuropathy symptoms.