x - linked adrenoleukodystrophy ( x - ald ) is the most common peroxisomal disorder , it is a rapidly progressive , neurodegenerative , and recessive disease that characteristically primarily affects the central nervous system white matter and the adrenal cortex1,2 ) . the prevalence of this condition is generally reported to be between 1:100,000 and 1:20,000 , although its overall frequency may be as high as 1:17,0003,4 ) . there are three major phenotypic forms of the disease , which is rapidly progressive childhood cerebral form , a milder adrenomyeloneuropathy in adults , and addison disease only5 ) . these clinical features are manifestation of impaired peroxismal -oxidation , which results in increased levels of saturated unbranched very long chain fatty acid ( vlcfa ) in the plasma and tissue , and particularly in the cholesterol ester , ganglioside , and proteolipid fractions of the brain white matter and in the cholesterol ester fraction of the adrenal cortex2 ) . x - ald is diagnosed with clinical , radiological , and serological tests , including tests for elevated plasma vlcfa such as c24:0 and c26:0 , and high c24:0/c22:0 and c26:0/c22:0 ratios1,2,3,4,5 ) , which are complemented with genetic analyses . the x - ald gene , abcd1 , has 10 exons and is located on chromosome xq28 , and was identified with a positional cloning strategy1 ) . to date , more than 600 abcd1 mutations have been identified . we report a 7.5-year - old korean boy with the childhood cerebral form of x - ald and an unpublished mutation in the abcd1 gene , despite normal plasma concentrations of vlcfa . a 7.5-year - old boy was admitted to to department of pediatrics , chungnam national university hospital with weakness of the bilateral lower extremities . the patient was a healthy child , born at term . he appeared to be healthy for his first six years , and his developmental milestones were normal . two months before admission , he occasionally fell over his foot and showed leg weakness . neurological examinations revealed that grade was four per five of motor - power at upper extremities and three per five at lower extremities . brain magnetic resonance imaging revealed a confluent t2-weighted high - signal - intensity lesion in the parieto - occipitofronto - temporal periventricular white matter , especially , around the atrium of the lateral ventricle , the posterior half of the corpus callosum , and posterior limb of internal capsule , and along the pyramidal tract of the brainstem ( fig . 1 ) . the proband was clinically suspected of suffering ald . laboratory tests revealed normal morning serum cortisol ( 8.72 g / dl ; normal , 5 - 25 g / dl ) and elevated adrenocorticotropic hormone ( 126.3 pg / ml ; normal , 9 - 52 pg / ml ) . the 1 g - synacthen test showed a peak cortisol response of 17.02 g / dl , confirming primary partial adrenal insufficiency . the fasting plasma levels of vlcfa , measured with gas chromatography - mass spectrometry , were : c22:0 , 11.954 mol / l ( normal , 0 - 96.300 mol / l ) ; c24:0 , 19.234 mol / l ( normal , 0 - 91.400 mol / l ) ; and c26:0 , 0.893 mol / l ( normal , 0 - 1.310 his c24:0/c22:0 and c26:0/c22:0 ratios were significantly elevated at 1.609 ( normal , 0 - 1.390 ) and 0.075 ( normal , 0 - 0.023 ) , respectively . genemic dna was extracted from peripheral whole blood samples collected from the patient and his family . the splice junctions and all coding regions of the abcd1 gene of the proband were amplified by polymerase chain reaction ( pcr ) using specific primers , but only exon 1 was amplified and sequenced in family members i-1 , i-2 , ii-2 , and ii-3 ( fig . the pcr products were directly sequenced using the same primer pairs and the bigdye terminator v3.1 cycle sequencing kit ( applied biosystems , foster city , ca , usa ) , according to the manufacturer 's instructions . the abcd1 gene in the proband revealed a missense mutation ( p.arg163leu ) caused by the nucleotide change 488g > t in exon 1 ( fig . the c.488g > t ( p.arg163leu ) substitution is a previously unpublished mutation in the abcd1 gene . he treated with lorenzo 's oil ( 3 - 4 spoon / day , 1 vial / mo ; scientific hospital supplies co. , san juan , trinidad and tobago ) , hydrocortisone , lovastatin , and coenzyme - q . after 2 years , he is in wheel - chair based doing , not bed - ridden . and he treats with rehabilitation for four limb rigidity and spasticity , swallowing difficulty , and decreased cognition . although this patient showed imaging findings of typical ald , his biochemical findings revealed vlcfa levels within normal limit . this mutation in the abcd1 gene , c.488g > t ( p.arg163leu ) in exon 1 , has been reported by dr . steinberg through the internet - accessible mutation database for x - ald ( http://www.x-ald.nl ) . this is the first published report of the c.488g > t mutation in exon 1 of the abcd1 gene . since the establishment of the x - ald database , 1236 mutations have been reported in the abcd1 gene , 582 ( 47% ) of which appear to be cryptic , but these mutations are not distributed evenly throughout the entire gene6 ) . they included 51% missense mutations , 11% nonsense mutations , 28% frameshift mutations , 6% amino acid insertions / deletions , and 3% deletion of one or more exons7 ) . there is no clear correlation between these mutations and the phenotypes of ald patients6,7 ) . the main biochemical abnormality and reliable diagnostic tool is a high plasma concentration of vlcfa in exclusively male x - ald patients . plasma vlcfa can be evaluated with three parameters : the concentration of c26:0 , the ratio of c26:0 to c22:0 , and the ratio of c24:0 to c22:0 . all three vlcfa parameters are elevated in 99% of male with x - ald8 ) . the database website for x - ald ( http://www.x-ald.nl ) demonstrated that approximately 10% to 20% of obligate carriers ( women with x - ald ) have normal levels of vlcfa . however , a normal plasma vlcfa level thus does not exclude heterozygosity for x - ald . in our patient , his plasma c26:0 , c24:0 , and c22:0 levels were all in the normal ranges , and only his c26:0/c22:0 and c24:0/c22:0 ratios were elevated . asian reports with abcd1 gene mutation in exon1 revealed that all males with x - ald had increased levels of vlcfa9 ) . interestingly , only our case showed normal range of vlcfa levels . because it is difficult to assess the correlation between phenotype and genotype , the role and meaning between missense mutation and normal levels of vlcfa has not solved in our case . kennedy et al.10 ) reported that the sensitivity of measures of plasma vlcfa levels is less than 100% for x - ald . they also categorized x - ald into three subgroups , according to the plasma vlcfa levels : " typical ald " , " normal " , and " in need of further study " . in the borderline results , that define the subgroup , " in need of further study " , our patient falls into the " in need of further study " subgroup of x - ald , and we designed this disease " atypical x - ald " . the concentrations of plasma vlcfa levels do not also correlated with the phenotypes of the ald patients8,10 ) . in conclusion , if the clinical suspicion of x - ald is strong plasma vlcfa levels are highly diagnostic measure . however , if the results for vlcfa are consistent with atypical ald , mutational analysis of the abcd1 gene can confirm the proper diagnosis of x - ald . we have reported a korean boy with atypical x - ald , confirmed by a previously unpublished datum from the x - ald database , c.488g > t ( p.arg163leu ) in exon 1 of abcd1 .
x - linked adrenoleukodystrophy ( x - ald ) is a rare peroxisomal disorder , that is rapidly progressive , neurodegenerative , and recessive , and characteristically primary affects the central nervous system white matter and the adrenal cortex . 
 x - ald is diagnosed basaed on clinical , radiological , and serological parameters , including elevated plasma levels of very long chain fatty acids ( vlcfa ) , such as c24:0 and c26:0 , and high c24:0/c22:0 and c26:0/c22:0 ratios . 
 these tests are complemented with genetic analyses . 
 a 7.5-year - old boy was admitted to department of pediatrics , chungnam national university hospital with progressive weakness of the bilateral lower extremities . 
 brain magnetic resonance imaging confirmed clinically suspected ald . 
 a low dose adrenocorticotropic hormone stimulation test revealed parital adrenal insufficiency . 
 his fasting plasma levels of vlcfa showed that his c24:0/c22:0 and c26:0/c22:0 ratios were significantly elevated to 1.609 ( normal , 0 - 1.390 ) and 0.075 ( normal , 0 - 0.023 ) , respectively . 
 genomic dna was extracted from peripheral whole blood samples collected from the patient and his family . 
 all exons of abcd1 gene were amplified by polymerase chain reaction ( pcr ) using specific primers . 
 amplified pcr products were sequenced using the same primer pairs according to the manufacturer 's instructions . 
 we identified a missense mutation ( p.arg163leu ) in the abcd1 gene of the proband caused by the nucleotide change 488g > t in exon 1 . 
 his asymptomatic mother carried the same mutation . 
 we have reported an unpublished mutation in the abcd1 gene in a patient with x - ald , who showed increased ratio of c24:0/c22:0 and c26:0/c22:0 , despite a normal vlcfa concentrations .