Editing Adrenoleukodystrophy (section)

==Diagnosis==
The clinical presentation of ALD can vary greatly, making diagnosis difficult.  With the variety of phenotypes, clinical suspicion of ALD can result from a variety of different presentations.  Symptoms vary based on the disease phenotype, and even within families or between twins.<ref name=omim>{{cite web|title=#300100 - Adrenoleukodystrophy |url=http://www.omim.org/entry/300100?search=x-ald&highlight=xald |archive-url=https://web.archive.org/web/20150924060356/http://www.omim.org/entry/300100?search=x-ald&highlight=xald |url-status=dead |archive-date=2015-09-24 |publisher=Johns Hopkins University |access-date=2012-06-27 }}</ref>  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]].  The concentration of unsaturated VLCFA, particularly 26 carbon chains is significantly elevated in males with ALD, even prior to the development of other symptoms.<ref name=plasmavlcfa>{{cite journal |last1=Moser |first1=Ann B. |last2=Kreiter |first2=Nancy |last3=Bezman |first3=Lena |last4=Lu |first4=Shou-En |last5=Raymond |first5=Gerald V. |last6=Naidu |first6=Sakkubai |last7=Moser |first7=Hugo W. |title=Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls |journal=Annals of Neurology |date=January 1999 |volume=45 |issue=1 |pages=100–110 |doi=10.1002/1531-8249(199901)45:1<100::aid-art16>3.0.co;2-u |pmid=9894883 |s2cid=24516921 }}</ref> Confirmation of ALD after positive plasma VLCFA determination usually involves molecular genetic analysis of ''ABCD1''.  In females, where plasma VLCFA measurement is not always conclusive (some female carriers will have normal VLCFA in plasma),<ref name="plasmavlcfa"/> molecular analysis is preferred, particularly in cases where the mutation in the family is known.<ref name=scriver /><ref name=genereviews />  Although the clinical phenotype is highly variable among affected males, the elevations of VLCFA are present in all males with an ''ABCD1'' mutation.<ref name=genereviews />

Because the characteristic elevations associated with ALD are present at birth, well before any symptoms are apparent, there have been methods developed<ref name=nbsxald2>{{cite journal |last1=Sandlers |first1=Yana |last2=Moser |first2=Ann B. |last3=Hubbard |first3=Walter C. |last4=Kratz |first4=Lisa E. |last5=Jones |first5=Richard O. |last6=Raymond |first6=Gerald V. |title=Combined extraction of acyl carnitines and 26:0 lysophosphatidylcholine from dried blood spots: Prospective newborn screening for X-linked adrenoleukodystrophy |journal=Molecular Genetics and Metabolism |date=March 2012 |volume=105 |issue=3 |pages=416–420 |doi=10.1016/j.ymgme.2011.11.195 |pmid=22197596 }}</ref><ref name=nbsxald3>{{cite journal |last1=Hubbard |first1=Walter C. |last2=Moser |first2=Ann B. |last3=Liu |first3=Anita C. |last4=Jones |first4=Richard O. |last5=Steinberg |first5=Steven J. |last6=Lorey |first6=Fred |last7=Panny |first7=Susan R. |last8=Vogt Jr. |first8=Robert F. |last9=Macaya |first9=Daniela |last10=Turgeon |first10=Coleman T. |last11=Tortorelli |first11=S |last12=Raymond |first12=GV |title=Newborn screening for X-linked adrenoleukodystrophy (X-ALD): Validation of a combined liquid chromatography–tandem mass spectrometric (LC–MS/MS) method |journal=Molecular Genetics and Metabolism |date=July 2009 |volume=97 |issue=3 |pages=212–220 |doi=10.1016/j.ymgme.2009.03.010 |pmid=19423374 }}</ref> in the interests of including it in [[newborn screening]] programs.<ref name=nbsxald>{{cite journal |last1=Raymond |first1=Gerald V. |last2=Jones |first2=Richard O. |last3=Moser |first3=Ann B. |s2cid=21323198 |title=Newborn Screening for Adrenoleukodystrophy |journal=Molecular Diagnosis & Therapy |date=16 August 2012 |volume=11 |issue=6 |pages=381–384 |doi=10.1007/BF03256261 |pmid=18078355 }}</ref>  One of the difficulties with ALD as a disease included in universal newborn screening is the difficulty in predicting the eventual phenotype that an individual will express.  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.<ref name=bergerreview /><ref name="transplantreview"/>  However, because most affected males will demonstrate adrenal insufficiency, early discovery and treatment of this symptom could potentially prevent complications and allow these patients to be monitored for other treatment in the future, depending on the progression of their disease.<ref name=nbsxald />

The Loes score is a rating of the severity of abnormalities in the brain found on MRI. It ranges from 0 to 34, based on a point system derived from the location and extent of disease and the presence of atrophy in the brain, either localized to specific points or generally throughout the brain. A Loes score of 0.5 or less is classified as normal, while a Loes score of 14 or greater is considered severe. It was developed by neuroradiologist Daniel J. Loes MD and is an important tool in assessing disease progression and the effectiveness of therapy.<ref>{{cite journal |last1=Loes |first1=Daniel J. |last2=Hite |first2=S |last3=Moser |first3=H |last4=Stillman |first4=A E |last5=Shapiro |first5=E |last6=Lockman |first6=L |last7=Latchaw |first7=R E |last8=Krivit |first8=W |date=October 1994 |title=Adrenoleukodystrophy: a scoring method for brain MR observations |journal=American Journal of Neuroradiology |volume=15 |issue=9 |pages=1761–1766 |pmid=7847225 |pmc=8333737 |url=http://www.ajnr.org/content/15/9/1761.abstract |access-date=January 17, 2013 |archive-date=September 1, 2015 |archive-url=https://web.archive.org/web/20150901213750/http://www.ajnr.org/content/15/9/1761.abstract |url-status=live }}</ref>