ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations

Probably not a substantial claim: may not pass S3 (load-bearing).

Childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN) account for approximately 80% of all X-ALD cases.

“Clinically, X-ALD is characterized by a striking and unpredictable variation in phenotypic expression, with childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN) accounting for approximately 80% of all cases [van Geel et al., 1997].”

• cites van Geel et al., 1997 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

In Saccharomyces cerevisiae, the two orthologs of ALDP, Pxa1p and Pxa2p, heterodimerize to form a functional ABC transporter.

“In the yeast Saccharomyces cerevisiae the two orthologs of ALDP, Pxa1p, and Pxa2p, heterodimerize to form a functional ABC transporter [Shani and Valle, 1996].”

• cites Shani and Valle, 1996 sourcePartly supported

  The paper’s opening text says Pxa1p and Pxa2p heterodimerize to form a yeast peroxisomal ABC transporter involved in fatty-acid β-oxidation. But the Discussion identifies Pxa1p as a putative ortholog of ALDP and suggests Pxa2p may instead be the yeast ortholog of PMP70. It does not support calling both proteins orthologs of ALDP. (LLM, conf=0.91)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In vitro, homodimerization and heterodimerization of the carboxyl-terminal halves of ALDP, ALDRP, and PMP70 have been demonstrated.

“In vitro, homodimerization, and heterodimerization of the carboxyl-terminal halves of ALDP, ALDRP, and PMP70 have been demonstrated using co-immunoprecipitation assays and the yeast two-hybrid system [Smith et al., 1999;Liu et al., 1999].”

• cites Smith et al., 1999 sourceNot checked — no full text of the source
• cites Liu et al., 1999 sourceSupported

May combine two claims.

There is no correlation between adrenal involvement and the type of neurologic involvement or the rate of neurologic progression in X-ALD.

“There is no correlation between adrenal involvement and the type of neurologic involvement or the rate of neurologic progression.”

Probably not a substantial claim: may not pass S3 (load-bearing).

As of June 2001, the X-ALD mutation database contained 406 mutations.

“As of June 2001, the X-ALD mutation database contained 406 mutations, which have been identified by various groups”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the Kennedy Krieger Institute series, the earliest age at which neurologic involvement became manifest was in a boy of two and a half years.

“In the Kennedy Krieger Institute series the earliest age at which neurologic involvement became manifest (a seizure) was in a boy of two and a half years.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Approximately 65% of male X-ALD patients remain free of neurologic symptoms by 10 years of age, but nearly all develop neurologic symptoms in adulthood.

“Approximately 65% of male X-ALD patients remain free of neurologic symptoms by 10 years of age, but nearly all develop neurologic symptoms in adulthood (Fig. 1).”

May combine two claims.

As shown in Table 1, cerebral forms of X-ALD occur most frequently in children, and AMN in adults.

“As shown in Table 1, the cerebral forms occur most frequently in children, and AMN in adults.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The majority of X-ALD database visits were from the United States and Canada (79%), 12% from Europe, 5% from Asia, 2% from both Australia and Latin America, and 0.5% from Africa.

“The majority of visits were from the United States and Canada (79%), 12% came from Europe, 5% from Asia, 2% from both Australia and Latin America, and 0.5% from Africa.”

Probably not a substantial claim: may not pass S3 (load-bearing).

At this time there is no evidence for major differences in the frequency of X-ALD in specific ethnic groups.

“At this time there is no evidence for major differences in the frequency of X-ALD in specific ethnic groups.”

May combine two claims.

There is a clustering of ABCD1 mutations in the transmembrane domain (40%), in the ATP-binding domain (30%), and in exon 5 (14%), with the remaining 16% spread throughout the gene.

“There is a clustering of mutations in the transmembrane domain (40%), in the ATP-binding domain (30%), and in exon 5 (14%).The remaining 16% of mutations are spread throughout the gene.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Motifs known to be associated with short deletion or insertion mutations have not been identified in the region flanking the 1415delAG mutation.

“Motifs known to be associated with short deletion or insertion mutations have not been identified in the region flanking this mutation.”

May combine two claims.

Amplicons exon1b and exon1c each harbor 20% of ABCD1 mutations, amplicon 8/9 covers 14%, and 13% of mutations can be identified in amplicon 5.

“Amplicons exon1b and exon1c each harbor 20% of mutations, amplicon 8/9 covers 14%, and 13% of mutations can be identified in amplicon 5.”

May combine two claims.

Of all X-ALD mutations in the database, 227 (55.9%) are missense, 110 (27.1%) are frame shift, 37 (9.1%) are nonsense, 16 (3.9%) are small in-frame amino acid insertions or deletions, and 16 (3.9%) are large deletions of one or more exons.

“Of all X-ALD mutations, 227 (55.9%) are missense, 110 (27.1%) are frame shift, 37 (9.1%) are nonsense, 16 (3.9%)are small in-frame amino acid insertions or deletions, and 16 (3.9%)are large deletions of one or more exons.”

May combine two claims.

No promoter mutations or complete ABCD1 gene deletions have been reported.

“No promoter mutations or complete gene deletions have been reported.”

May combine two claims.

The 216 informative X-ALD cell lines represent 78 non-recurrent ABCD1 mutations, and 62 of these (79.5%) result in absence of detectable ALDP.

“The 216 informative cell lines represent 78 non-recurrent mutations.Sixty two of these (79.5%) result in absence of detectable protein levels.”

May combine two claims.

A family in The Netherlands has the missense mutation R389H and normal levels of ALDP; all heterozygotes in this kindred are asymptomatic, and all male patients are either asymptomatic at old age or show mild phenotypes including gonadal insufficiency and AMN without cerebral involvement.

“For example, a family has been identified in The Netherlands with a missense mutation, R389H, and normal levels of ALDP.All heterozygotes in this kindred are asymptomatic, and all male patients are either asymptomatic at old age or show mild phenotypes including gonadal insufficiency and AMN without cerebral involvement.”

May combine two claims.

In some ABCD1 exons (1a, 2, 4, 5, and 10) fewer than expected missense mutations have been identified, while in other exons (1b, 1c, 6, 7, 8, and 9) more than expected missense mutations were found.

“In some exons (1a, 2, 4, 5, and 10) fewer than expected have been identified, while in other exons (1b, 1c, 6, 7, 8, and 9) more than expected missense mutations were found.”

May combine two claims.

Single base pair substitutions or point mutations represent 69.1% of X-ALD mutations, and the remaining 30.9% are deletions or insertions of one or more nucleotides.

“Single base pair substitutions or point mutations represent the majority (69.1%) of mutations.The remaining 30.9% are deletions or insertions of one or more nucleotides.”

May combine two claims.

A total of 227 missense mutations have been reported in the ABCD1 gene; expression data are available on 137 missense mutations, representing 52 unique missense mutations.

“A total of 227 missense mutations have been reported in the ABCD1 gene.Expression data is available on 137 missense mutations, which represent 52 unique missense mutations.”

May combine two claims.

Only 31% of all non-recurrent missense mutations did not affect ALDP stability, 11% resulted in strongly reduced expression levels, and 58% resulted in unstable and absent levels of ALDP.

“Only 31% of all non-recurrent missense mutations did not affect the stability of ALDP, 11% resulted in strongly reduced expression levels, and 58% resulted in unstable and absent levels of ALDP.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

No disease has been associated yet with mutations in the ABCD2 gene.

“No disease has been associated yet with mutations in the ABCD2 gene.”

May combine two claims.

84 of the 91 (92%) identified disease-causing unique missense mutations in ALDP affect amino acid residues that are identical between ALDP and ALDRP, whereas only 61 are expected on the basis of the 66% sequence identity.

“This is supported by the observation that 84 of the 91 (92%) identified disease causing unique missense mutations in ALDP affect amino acid residues that are identical between ALDP and ALDRP, whereas only 61 are expected to be found on the basis of the 66% sequence identity.”

May combine two claims.

Screening of 4,169 at-risk family members led to the identification of 594 additional X-ALD hemizygotes, 250 of whom were asymptomatic, and of 1,270 heterozygotes.

“Screening of 4,169 at-risk family members led to the identification of 594 additional X-ALD hemizygotes, 250 of whom were asymptomatic, and of 1,270 heterozygotes.”

May combine two claims.

Neurologic deficits in X-ALD almost never develop before three years of age and in most instances considerably later.

“neurologic deficits almost never develop before three years of age and in most instances considerably later (Fig. 1)”

Probably not a substantial claim: may not pass S3 (load-bearing).

Approximately 50% of women heterozygous for X-ALD develop AMN-like symptoms in middle age or later.

“Approximately 50% of women heterozygous for X-ALD develop AMN-like symptoms in middle age or later.”

• cites Moser, 1997 sourceNot checked — no full text of the source
• cites Restuccia et al., 1997 sourceNot checked — no full text of the source
• cites el Deiry et al., 1997 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Seventy percent of male X-ALD patients have primary adrenocortical insufficiency (Addison's disease).

“Seventy percent of male X-ALD patients have primary adrenocortical insufficiency (Addison's disease) [van Geel et al., 2001].”

• cites van Geel et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

ABCD1 encodes a peroxisomal ATP-binding cassette transporter, ALDP, and not VLCS.

“This gene encodes a peroxisomal ATP-binding cassette transporter, the ALD protein (ALDP), and not VLCS [Mosser et al., 1993].”

• cites Mosser et al., 1993 sourceNot checked — no full text of the source

May combine two claims.

At least 20% of patients with AMN will develop cerebral involvement at a later age, which may have the same rapidly progressive course as in CCALD.

“A study by van Geel et al. [2001], showed that at least 20% of patients with AMN will develop cerebral involvement at a later age, which may have the same rapidly progressive course as in CCALD.”

• cites van Geel et al., 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

AMN is the most common X-ALD phenotype.

“AMN is the most common X-ALD phenotype [van Geel et al., 1994].”

• cites van Geel et al., 1994 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The minimum incidence of X-ALD in males is 1:21,000.

“X-linked adrenoleukodystrophy (X-ALD: MIM# 300100) is the most common peroxisomal disorder with a minimum incidence of 1:21,000 males [Bezman et al., 2001].”

• cites Bezman et al., 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

X-ALD is the most common peroxisomal disorder.

“X-linked adrenoleukodystrophy (X-ALD: MIM# 300100) is the most common peroxisomal disorder with a minimum incidence of 1:21,000 males [Bezman et al., 2001].”

• cites Bezman et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

The predicted ALDP from the 1415delAG mutation lacks the ATP-binding domain and is both unstable and inactive.

“The predicted ALDP lacks the ATP-binding domain and is both unstable and inactive.”

May combine two claims.

X-ALD fibroblasts transfected with an ALDP deletion mutant lacking amino acids 693 to 745 had similar β-oxidation activity as X-ALD fibroblasts transfected with wild type ALDP cDNA, and deletion of the 52 carboxyl-terminal amino acids did not affect protein stability.

“Smith and coworkers [1999] demonstrated that X-ALD fibroblasts transfected with a cDNA construct encoding an ALDP deletion mutant that lacks amino acids 693 to 745 (ALDPdel693-745) had similar β-oxidation activity as X-ALD fibroblasts transfected with a wild type ALDP cDNA construct.In addition, the deletion of the 52 carboxyl-terminal amino acids did not affect the stability of the protein.”

• cites Smith et al., 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The ABCD1 gene is approximately 19 kb long, contains 10 exons, and encodes a protein of 745 amino acids.

“The gene is approximately 19 kb long, contains 10 exons and encodes a protein of 745 amino acids.”

• cites Mosser et al., 1993 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Asymptomatic X-ALD patients and those with the AMN or Addison-only phenotype continue to be under-diagnosed.

“Asymptomatic patients and those with the AMN or “Addison-only” phenotype continue to be under-diagnosed.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The ABCD1 gene is located on Xq28.

“The X-ALD gene (ABCD1), identified by positional cloning strategies, is located on Xq28 [Mosser et al., 1993].”

• cites Mosser et al., 1993 sourceNot checked — no full text of the source

May combine two claims.

Cerebral involvement and adrenocortical insufficiency are rare in women heterozygous for X-ALD.

“Cerebral involvement and adrenocortical insufficiency are rare [Moser, 1997;Restuccia et al., 1997;el Deiry et al., 1997].”

• cites Moser, 1997 sourceNot checked — no full text of the source
• cites Restuccia et al., 1997 sourceNot checked — no full text of the source
• cites el Deiry et al., 1997 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The fourth ABCD1 polymorphism is present at cDNA position 2246, eight nucleotides downstream of the stop codon (2246C/G).

“The fourth polymorphism is present at cDNA position 2246, eight nucleotides downstream of the stop codon (2246C/G) [Kemp et al., 1994].”

• cites Kemp et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

The frequency of women heterozygous for X-ALD cannot be determined reliably by surveys because most affected women remain asymptomatic until middle age, and symptomatic women often remain undiagnosed unless they have a symptomatic affected male relative.

“The frequency of women heterozygous for X-ALD cannot be determined reliably by surveys because most affected women remain asymptomatic until middle age, and those who are symptomatic often remain undiagnosed unless they have a symptomatic affected male relative.”

May combine two claims.

The region of ALDP downstream of amino acid 693 does not appear to be important for protein stability or normal VLCFA β-oxidation.

“Therefore, this region of the protein does not appear to be important for protein stability or normal VLCFA β-oxidation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Earlier reports from The Netherlands, Australia, and Spain reported an X-ALD incidence of approximately 1:100,000.

“In earlier reports from The Netherlands, Australia, and Spain [Bezman and Moser, 1998], an incidence of approximately 1:100,000 was reported.”

• cites Bezman and Moser, 1998 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The discrepancy between the 1:21,000 and 1:100,000 X-ALD incidence numbers is not understood but is probably due to incomplete ascertainment.

“The discrepancy between the two incidence numbers is not understood, but is probably due to incomplete ascertainment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The most recent X-ALD incidence value from France is 1:15,000 and may be the most accurate value available so far.

“The most recent value from France, where the referral network has been centralized to an increasing extent, is 1:15,000 (P.Aubourg, personal communication), and may be the most accurate value available so far.”

• cites P.Aubourg, personal communicationNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

A similar X-ALD frequency of 1:20,000 was reported in France.

“A similar frequency (1:20,000) was reported in France [Dubois-Dalcq et al., 1999].”

• cites Dubois-Dalcq et al., 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Reports of varying phenotypes in identical twins suggest that environmental factors may be involved in X-ALD phenotypic variation.

“However, reports of varying phenotypes in identical twins suggest that environmental factors may be involved [Sobue et al., 1994;Korenke et al., 1996].”

• cites Sobue et al., 1994 sourceNot checked — no full text of the source
• cites Korenke et al., 1996 sourceNot checked — no full text of the source

May combine two claims.

The exon 5 hot spot mutation involves deletion of two nucleotides (AG) at cDNA position 1415-16, causing a frame shift at Glu471 and a premature stop codon at position 554.

“This mutation involves the deletion of two nucleotides (AG) at cDNA position 1415-16.This results in a frame shift at amino acid residue Glu471 (fs E471) and a premature stop codon at position 554.”

• cites Kemp et al., 1994 sourceNot checked — no full text of the source
• cites Kok et al., 1995 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

ALDP, with one membrane spanning region and one ATP-binding domain, has the structure of an ABC half-transporter.

“ALDP with one membrane spanning region and one ATP-binding domain has the structure of an ABC half-transporter.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The nucleotide binding fold of ALDP is located toward the cytoplasmic surface of the peroxisomal membrane.

“The nucleotide binding fold of ALDP is located toward the cytoplasmic surface of the peroxisomal membrane [Mosser et al., 1994;Watkins et al., 1995].”

• cites Mosser et al., 1994 sourceNot checked — no full text of the source
• cites Watkins et al., 1995Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

ALDRP is encoded by the ABCD2 gene, which is located on chromosome 12q11.12.

“The protein is encoded by the ABCD2 gene, which is located on chromosome 12q11.12[Savary et al., 1997].”

• cites Savary et al., 1997 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In Drosophila melanogaster, uptake of metabolic precursors necessary for synthesis of brown and red eye pigments in pigment cells is controlled by different heterodimer combinations of ABC half-transporters in the cell membrane.

“In the fruit fly Drosophila melanogaster, the uptake of metabolic precursors that are necessary for the synthesis of the brown and red eye pigments in pigment cells is controlled by the presence of different heterodimer combinations of ABC half-transporters in the cell membrane of these cells.”

• cites Ewart et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

ALDRP shares 66% identity and 88% homology with ALDP.

“ALDRP shares 66% identity and 88% homology with ALDP.”

May combine two claims.

The disease-causing effect of at least some X-ALD missense mutations may be due to inhibition of dimer formation, and this is likely to affect protein stability.

“The disease-causing effect of at least some of these missense mutations may be due to inhibition of dimer formation, and this is likely to affect protein stability.”

May combine two claims.

Overexpression of ALDRP cDNA in human and mouse X-ALD fibroblasts completely restores VLCFA β-oxidation and results in normal levels of VLCFAs.

“Overexpression of ALDRP cDNA in human and mouse X-ALD fibroblasts completely restores VLCFA β-oxidation and results in normal levels of VLCFAs [Kemp et al., 1998;Netik et al., 1999].”

• cites Kemp et al., 1998 sourceNot checked — no full text of the source
• cites Netik et al., 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Red color pigment precursors are imported by the guanine transporter that contains heterodimers of subunits encoded by the white and brown genes.

“Red color pigment precursors are imported by the guanine transporter that contains heterodimers of subunits encoded by the white and brown genes.”

• cites Ewart et al., 1994 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Proteins from the white and scarlet genes heterodimerize to form the tryptophan transporter, involved in the import of metabolites for the synthesis of brown color pigments.

“Proteins from the white and scarlet genes heterodimerize to form the tryptophan transporter, involved in the import of metabolites for the synthesis of brown color pigments [Ewart et al., 1994].”

• cites Ewart et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

In brain, ALDP is expressed predominantly in glial cells, while ALDRP is primarily expressed in neurons.

“In brain, ALDP is expressed predominantly in glial cells, while ALDRP is primarily expressed in neurons.”

May combine two claims.

For two missense mutations in functional regions of the ALDP ATP-binding domain, S606L resulted in decreased ATP-binding capacity and G512S resulted in reduced ATPase activity.

“For two missense mutations located in functional regions of the ATP-binding domain it was demonstrated that the mutations resulted in either decreased ATPbinding capacity (S606L) or reduced ATPase activity (G512S) [Roerig et al., 2001].”

• cites Roerig et al., 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The nucleotide-binding fold of ALDP acts as an ATP-binding subunit with ATPase activity.

“It was demonstrated recently that the nucleotide-binding fold of ALDP acts as an ATP-binding subunit with ATPase activity [Roerig et al., 2001].”

• cites Roerig et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

PMP70 and PMP69/P70R share 38% and 27% identity, respectively, with ALDP.

“The two other members of the peroxisomal ABC half-transporter sub-family, PMP70, and PMP69/P70R, are more distantly related; they share 38% and 27% identity, respectively.”

May combine two claims.

Among the three peroxisomal ALDP homologs, ALDRP is most closely related and of greatest interest with respect to X-ALD.

“Of the three peroxisomal ALDP homologs that have been identified, ALDRP is most closely related and of greatest interest with respect to X-ALD.”

Probably not a substantial claim: may not pass S3 (load-bearing).

ALDP belongs to the superfamily of ABC transmembrane transporter proteins.

“ALDP belongs to the superfamily of ABC transmembrane transporter proteins [Mosser et al., 1993].”

• cites Mosser et al., 1993 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Three additional mammalian peroxisomal ABC half-transporters closely related by nucleic acid and protein sequence have been identified: ALDRP, PMP70, and PMP69 (or P70R).

“Three additional mammalian peroxisomal ABC half-transporters closely related by nucleic acid and protein sequence have been identified: ALDRP, an ALDP-related protein [Lombard-Platet et al., 1996;Holzinger et al., 1997a]; PMP70, a 70-kDa peroxisome membrane protein [Kamijo et al., 1990;Gartner et al., 1992]; and PMP69 (or P70R), a 69-kDa peroxisome membrane protein [Shani et al., 1997;Holzinger et”

• cites Lombard-Platet et al., 1996 sourceNot checked — no full text of the source
• cites Holzinger et al., 1997aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Kamijo et al., 1990 sourceNot checked — no full text of the source

May combine two claims.

Over-expression of VLCS alone in human X-ALD fibroblasts does not improve VLCFA β-oxidation, while coexpression of both VLCS and ALDP in X-ALD fibroblasts increased VLCFA β-oxidation synergistically.

“Over-expression of VLCS alone in human X-ALD fibroblasts does not improve VLCFA β-oxidation, while coexpression of both VLCS and ALDP in X-ALD fibroblasts increased VLCFA β-oxidation synergistically [Steinberg et al., 1999].”

• cites Steinberg et al., 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Functional eukaryotic ABC transporters contain two homologous halves, each with a transmembrane domain and an ATP-binding domain.

“Functional eukaryotic ABC transporters contain two homologous halves, each with a transmembrane domain (TMD) and an ATPbinding domain (ATP) [Higgins, 1992].”

• cites Higgins, 1992 sourceNot checked — no full text of the source

May combine two claims.

Increased VLCFA levels occur also in patients with other peroxisomal disorders, but these can be distinguished on the basis of clinical manifestations and additional laboratory analyses using a laboratory flow chart.

“Increased VLCFA levels occur also in patients with other peroxisomal disorders, such as the disorders of peroxisome biogenesis and patients with other defects of peroxisomal β-oxidation, but these can be distinguished on the basis of clinical manifestations and additional laboratory analyses using a laboratory flow chart as described by Wanders and associates [Wanders et al., 2001].”

• cites Wanders et al., 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

These considerations, combined with a relatively high incidence, make X-ALD a candidate for neonatal mass screening in males.

“These considerations, combined with a relatively high incidence, make X-ALD a candidate for neonatal mass screening in males.”

May combine two claims.

Extended family screening can lead to the identification of males at a time when therapy has the greatest chance of being successful, and the identification of heterozygotes can aid disease prevention through genetic counseling.

“Thus, extended family screening can lead to the identification of males at a time when therapy has the greatest chance of being successful, and the identification of heterozygotes can aid disease prevention through genetic counseling.”

Classified as probably not a substantial claim. May combine two claims.

Neonatal screening for X-ALD in males would be of value since it would permit early identification of adrenocortical insufficiency and cerebral involvement, and consequently would facilitate therapeutic intervention.

“Neonatal screening for X-ALD in males would be of value since it would permit early identification of adrenocortical insufficiency and cerebral involvement, and consequently would facilitate therapeutic intervention.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Gonadal mosaicism has been reported in X-linked disorders.

“Gonadal mosaicism has been reported in Xlinked disorders [Bowling et al., 1999]”

• cites Bowling et al., 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Gonadal mosaicism theoretically can occur in mothers without a mutation in the ABCD1 gene who have children with X-ALD.

“and theoretically can occur in mothers without a mutation in the ABCD1 gene who have children with X-ALD.”