Editing Adrenoleukodystrophy (section)

==Pathogenesis==

The exact cause for the varied collection of symptoms found in the different ALD phenotypes is not clear.  The [[white matter]] of the brain, the [[Leydig cells]] of the [[testes]] and the adrenal cortex are the most severely affected systems.<ref name=scriver /> The excess VLCFA can be detected in almost all tissues of the body, despite the localization of symptoms.<ref name=scriver /> 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.<ref name="transplantreview"/>  The levels of VLCFA can be normalized by treatment with [[Lorenzo's oil]], but this does not alter the progression of the disease.<ref name=bergerreview />  It is unclear whether the accumulation of VLCFA is associated with the pathogenesis of the disease in a specific way, or if it is a biochemical phenotype, useful for identification.<ref name=scriver /> Several studies link inflammation from viral infection or head trauma to development or worsening of symptoms.<ref>{{Cite journal |last1=Raymond |first1=Gerald V. |last2=Seidman |first2=Roberta |last3=Monteith |first3=Teshamae S. |last4=Kolodny |first4=Edwin |last5=Sathe |first5=Swati |last6=Mahmood |first6=Asif |last7=Powers |first7=James M. |date=March 2010 |title=Head trauma can initiate the onset of adreno-leukodystrophy |url=https://linkinghub.elsevier.com/retrieve/pii/S0022510X09009460 |journal=Journal of the Neurological Sciences |language=en |volume=290 |issue=1–2 |pages=70–74 |doi=10.1016/j.jns.2009.11.005|pmid=19945717 |url-access=subscription }}</ref><ref>{{Cite journal |last1=Bouquet |first1=Floriane |last2=Dehais |first2=Caroline |last3=Sanson |first3=Marc |last4=Lubetzki |first4=Catherine |last5=Louapre |first5=Céline |date=December 2015 |title=Dramatic worsening of adult-onset X-linked adrenoleukodystrophy after head trauma |url=https://www.neurology.org/doi/10.1212/WNL.0000000000002173 |journal=Neurology |language=en |volume=85 |issue=22 |pages=1991–1993 |doi=10.1212/WNL.0000000000002173 |pmid=26537054 |issn=0028-3878|url-access=subscription }}</ref><ref>{{Cite journal |last1=Budhram |first1=Adrian |last2=Pandey |first2=Sachin K. |date=September 2017 |title=Activation of Cerebral X-linked Adrenoleukodystrophy After Head Trauma |url=https://www.cambridge.org/core/product/identifier/S031716711700052X/type/journal_article |journal=Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques |language=en |volume=44 |issue=5 |pages=597–598 |doi=10.1017/cjn.2017.52 |pmid=28534457 |issn=0317-1671}}</ref><ref>{{Cite journal |last1=Wang |first1=Qiu-Hong |last2=Wang |first2=Jing |last3=Wang |first3=Yang-Yang |last4=He |first4=Wen |last5=Feng |first5=Chen |last6=Gao |first6=Jing |last7=Lu |first7=Qian |last8=Wang |first8=Yi |last9=Dun |first9=Shuo |last10=Zhang |first10=Qi |last11=Zou |first11=Li-Ping |date=March 2024 |title=Accelerated Course of Cerebral Adrenoleukodystrophy After Coronavirus Disease 2019 Infection |url=https://linkinghub.elsevier.com/retrieve/pii/S0887899423004629 |journal=Pediatric Neurology |language=en |volume=152 |pages=87–92 |doi=10.1016/j.pediatrneurol.2023.12.021|pmid=38237318 |url-access=subscription }}</ref>