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Cited by 7Retinal Development and DisordersMetabolism and Genetic DisordersHereditary Neurological Disorders

ACBD5‐related retinal dystrophy with leukodystrophy due to novel mutations in ACBD5 and with additional features including ovarian insufficiency

Open access
Rudaks, Laura Ivete, Triplett, James, Morris, Katrina, Reddel, Stephen, Worgan, Lisa·2024·American Journal of Medical Genetics Part A
DOI 10.1002/ajmg.a.63433
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Abstract

Acyl‐CoA‐binding domain‐containing protein 5‐related retinal dystrophy with leukodystrophy (ACBD5) is a peroxisomal disorder due to deficiency of ACBD5. Presenting features include retinal dystrophy, progressive leukodystrophy, and ataxia. Only seven cases of ACBD5‐related retinal dystrophy have been reported in the literature to date, including one other case diagnosed in adulthood. Here we report a case with novel compound heterozygous ACBD5 mutations, presenting with the common features of rod monochromatism and progressive leukodystrophy with spasticity and ataxia. Additional novel clinical features included head and neck tremor and ovarian insufficiency. The patient's symptoms were present since infancy, but a diagnosis was only reached in adulthood when whole exome sequencing was performed. This case, which reports two novel mutations and additional clinical manifestations, contributes to the emerging phenotype of ACBD5‐related retinal dystrophy with leukodystrophy, and delineation of the natural history and disease progression.

AI snapshot

Written from the paper’s full text.

TL;DR

This case report describes a 30-year-old woman with ACBD5-related retinal dystrophy with leukodystrophy, diagnosed at age 27 after trio exome sequencing identified two novel compound heterozygous truncating *ACBD5* variants. It expands the phenotype with dystonic head/neck tremor and primary ovarian insufficiency and documents progressive retinal, neurologic, and imaging findings.

Key findings

  • The patient had novel compound heterozygous truncating *ACBD5* variants: c.979G>T, p.Gly327* and c.399del, p.Ile134Leufs*6; both were absent from gnomAD and ClinVar and classified pathogenic by ACMG criteria (PVS1, PM2, PM3).
  • Core features included rod monochromatism diagnosed at 18 months, nystagmus from 2 months, progressive ataxia and lower-limb spasticity/weakness from 2 years, wheelchair use by 6 years, dysarthria from 3 years, dysphagia from 10 years, urinary incontinence by 12 years, and urinary retention requiring suprapubic catheter at 25 years.
  • Additional previously unreported features were dystonic head and neck tremor and primary ovarian insufficiency; at age 23, estradiol was low at 29.7 pmol/L with elevated LH 85.3 IU/L and FSH 197.4 IU/L.
  • Plasma VLCFAs at age 15 were normal: hexacosanoate 0.83 μmol/L [0.33–1.13], C26:C22 ratio 0.020 [0.007–0.024], and C24:22 ratio 0.97 [0.60–1.02]. Serial MRI showed progressive leukodystrophy and atrophy, with Evans index 22.6% at age 10, 27.0% at age 18, and 27.7% at age 27; third ventricular width was 6.7 mm at age 18 and 8.5 mm at age 27.

Methods

  • Single case report of a 30-year-old female born to non-consanguineous parents of Scottish and Irish heritage, with one healthy brother.
  • Clinical data included serial brain and spinal MRI, ERG, electrophysiology, hormonal testing, plasma VLCFA testing, chromosomal microarray, and trio exome sequencing.
  • Trio exome sequencing was performed at SEALS Genetics with reads aligned to GRCh38, variant calling via Dragen Server in Illumina Basespace, and filtering/prioritization/reporting using the in-house GAIA pipeline; variants were classified using ACMG criteria.

Limitations

  • The paper does not include a dedicated limitations section; it states that comparable 3D imaging for volumetrics was not available and that MRI studies were performed on three different scans with variation in slice width and alignment, so they are not directly comparable.
  • As a single case report, the findings cannot establish prevalence, genotype–phenotype correlation, or causality for the newly reported features; this limitation is evident from the design.
  • The association of ovarian insufficiency with the peroxisomal disorder is hypothesized, with no alternative cause identified, but not functionally proven; plasma VLCFAs were normal in this case despite being typically abnormal in ACBD5-related disease.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/ajmg.a.63433

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

18 of 31 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    The c.979G > T variant is not present in gnomAD or ClinVar.

    “The variant is not present in the normal population database gnomAD, nor the ClinVar database.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Karczewski et al., 2020 source

      The Data availability section describes gnomAD and its variant browser, but does not report whether c.979G>T is present. Searches for “c.979G > T,” “979G,” and the variant’s absence from ClinVar found no passage addressing either database lookup. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites Landrum et al., 2018 source

      The VCV accession numbers section discusses a different, explicitly identified variant, while the New and improved VCF files section describes ClinVar data fields. Searches for c.979G>T, 979G, and gnomAD found no passage establishing whether the claimed variant is absent from either database; page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Findingcitation

    The c.399del variant is not present in gnomAD or ClinVar.

    “This variant is not present in gnomAD, or ClinVar databases”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Karczewski et al., 2020 source

      The Data availability section describes the gnomAD dataset and its variant browser, but does not report whether c.399del is present. Searches of our copy for “c.399del” and “ClinVar” found no passage establishing the variant’s absence from either database. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites Landrum et al., 2018 source

      The ‘VCV accession numbers for Variation IDs’ section discusses a different variant, NM_007294.3:c.4038_4041delAAGA. Searches for c.399del and gnomAD found no passage assessing whether c.399del is present in either database; the paper’s description of ClinVar cannot establish its absence. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Findingcitation

    The c.399del variant is classified as pathogenic by ACMG criteria (PVS1, PM2, PM3).

    “This variant is classified as pathogenic by ACMG criteria (PVS1, PM2, PM3)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Richards et al., 2015 source
  • Premisecitation

    Other features of ataxia, dysarthria, cleft palate, facial dysmorphisms, progressive microcephaly, and seizures are reported sporadically in ACBD5-related retinal dystrophy with leukodystrophy.

    “Other features of ataxia, dysarthria, cleft palate, facial dysmorphisms, progressive microcephaly, and seizures are reported sporadically (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Abu-Safieh et al., 2013 source

      The Results section ('Exome as a discovery tool for novel RD genes'; page not provided) reports an ACBD5 variant in siblings with cone-rod dystrophy, psychomotor delay, and significant white-matter involvement. It does not report the listed additional features—ataxia, dysarthria, cleft palate, facial dysmorphisms, progressive microcephaly, or seizures—so this source supports the disease context but not those features. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Bartlett et al., 2021 source
    • cites Ferdinandusse et al., 2017 source
  • Premisecitation

    The condition was first identified in three affected siblings presenting with cone-rod dystrophy, spastic paraparesis, psychomotor delay, and leukodystrophy.

    “This condition was first identified in three affected siblings presenting with cone-rod dystrophy, spastic paraparesis, psychomotor delay, and leukodystrophy (Abu-Safieh et al., 2013).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Abu-Safieh et al., 2013 source

      The Results section (page not provided) describes three affected siblings in Family CRSPW with cone-rod dystrophy, psychomotor delay, and significant white-matter involvement. The Discussion calls the association apparently novel, but our copy does not identify spastic paraparesis or explicitly diagnose leukodystrophy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 11
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Rod-cone dystrophy, delayed or regression of motor development, progressive cognitive decline, and imaging features of a progressive leukodystrophy are common features of ACBD5-related retinal dystrophy with leukodystrophy.

    “Rod-cone dystrophy, delayed or regression of motor development, progressive cognitive decline, and imaging features of a progressive leukodystrophy are common features (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Abu-Safieh et al., 2013 source

      The Results section (page unavailable) reports cone-rod dystrophy, psychomotor delay, and significant white-matter involvement in three siblings with an ACBD5 variant. It does not describe rod-cone dystrophy, motor regression, progressive cognitive decline, or imaging evidence of progressive leukodystrophy, nor does this single family establish those findings as common features. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Bartlett et al., 2021 source
    • cites Ferdinandusse et al., 2017 source

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

    Findingcitation

    Early motor development was normal in this case, but can be variable, with both normal and delayed milestones reported in other cases.

    “Early motor development was normal in our case, but can be variable, with both normal and delayed milestones reported in other cases (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Abu-Safieh et al., 2013 source

      The Results section (“Exome as a discovery tool for novel RD genes”; page unavailable) reports psychomotor delay in three affected siblings, supporting the delayed-development part of the cited statement. It does not report normal motor milestones in other cases or establish the claimed variation between normal and delayed milestones. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites Bartlett et al., 2021 source
    • cites Ferdinandusse et al., 2017 source

  • May combine two claims.

    Premisecitation

    Peroxisomes proliferate or decrease in number in response to environmental stimuli, while impaired membrane growth related to ACBD5-deficiency may affect this dynamic process and reduce the responsiveness of the peroxisomal system to physiologic stressors.

    “Peroxisomes proliferate or decrease in number in response to environmental stimuli, while impaired membrane growth related to ACBD5-deficiency may affect this dynamic process and reduce the responsiveness of the peroxisomal system to physiologic stressors (Darwisch et al., 2020;Schrader et al., 2006).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Darwisch et al., 2020 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites Schrader et al., 2006 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Only seven cases of ACBD5-related retinal dystrophy with leukodystrophy have been reported to date, including one other case diagnosed in adulthood.

    “Only seven cases of ACBD5-related retinal dystrophy have been reported in the literature to date, including one other case diagnosed in adulthood.”
    • Also stated in: § 1 | INTRODUCTION · plain
      “Seven cases of ACBD5-related retinal dystrophy with leukodystrophy have been reported to date, including one case diagnosed as an adult (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Abu-Safieh et al., 2013 source

      The Results section reports three affected siblings with cone-rod dystrophy, significant white-matter involvement, and an ACBD5 variant. It does not establish that seven cases had been reported in the literature or identify a case diagnosed in adulthood. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites Bartlett et al., 2021 source
    • cites Ferdinandusse et al., 2017 source

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

    Premisecitation

    Peroxisomes are suspected to play a role in the maintenance of ovarian redox balance, preventing reactive oxygen species-related meiotic arrest and permitting successful progression through folliculogenesis.

    “Peroxisomes are suspected to play a role in the maintenance of ovarian redox balance, preventing reactive oxygen species-related meiotic arrest and permitting successful progression through folliculogenesis (Wang et al., 2022).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Wang et al., 2022 source

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

    Premisecitation

    Peroxisomes are thought to be involved in gonadotropic steroid and cholesterol synthesis.

    “Ovarian peroxisomal function remains incompletely understood, but peroxisomes are thought to be involved in gonadotropic steroid and cholesterol synthesis (Wang et al., 2022).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Wang et al., 2022 source

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

    Premisecitation

    Premature ovarian insufficiency has been previously described in association with other peroxisomal disorders, although is not a common feature.

    “Premature ovarian insufficiency has been previously described in association with other peroxisomal disorders, although is not a common feature (Karlberg et al., 2018;Wang et al., 2022).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Karlberg et al., 2018 source
    • cites Wang et al., 2022 source

      Section 6 (page unavailable) describes smaller ovaries and infertility in female peroxisomal gene-knockout mice, supporting an association between peroxisomal dysfunction and impaired ovarian function. It does not describe premature ovarian insufficiency in people with peroxisomal disorders or establish that it is uncommon; its statement that few studies investigate the female ovary concerns the research literature, not how often the condition occurs. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Further hypothesized roles of peroxisomes include maintenance of fatty acid species homeostasis, and provision of ATP and nutrition through beta-oxidation.

    “Further hypothesized roles include maintenance of fatty acid species homeostasis, and provision of ATP and nutrition through beta-oxidation (Wang et al., 2022).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Wang et al., 2022 source

      Section 4.2 proposes that peroxisomes might regulate fatty-acid species homeostasis. It also says peroxisomal β-oxidation does not directly provide cellular ATP: peroxisomes shorten fatty acids for further metabolism in mitochondria, where β-oxidation generates ATP. The claimed provision of ATP and nutrition by peroxisomes is therefore overstated. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The patient developed urinary incontinence by age 12, which progressed to urinary retention, requiring a suprapubic catheter insertion at 25 years.

    “She developed urinary incontinence by age 12, which later progressed to urinary retention, requiring a suprapubic catheter insertion at 25 years.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    From 2 years of age, the patient demonstrated progressive ataxia, lower limb spasticity, and weakness, with superimposed episodes of reversible deterioration with fevers.

    “From 2 years of age, she demonstrated progressive ataxia, lower limb spasticity, and weakness, with superimposed episodes of reversible deterioration with fevers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The patient's cognition declined over time, and from adolescence she developed prominent emotional lability and anxiety.

    “declined over time, and from adolescence she has developed prominent emotional lability and anxiety.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    The proband carries novel compound heterozygous truncating variants in ACBD5.

    “Here we report a case with novel compound heterozygous ACBD5 mutations, presenting with the common features of rod monochromatism and progressive leukodystrophy with spasticity and ataxia.”
    • Also stated in: § 1 | INTRODUCTION · plain
      “Here we report a case, diagnosed at age 27, with novel compound heterozygous ACBD5 mutations and previously unreported clinical features.”
    • Also stated in: § 1 | INTRODUCTION · plain
      “This identified compound heterozygous truncating variants in ACBD5.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Spinal MRI at 12 and 18 years demonstrated progressive atrophy of the cord, especially in the thoracic region, with relative sparing of cervical and distal lumbar expansions, most marked at T4-7 levels, with associated subtle abnormal intramedullary T2 signal.

    “Spinal MRI completed at 12 and 18 years of age demonstrated progressive atrophy of the cord, especially in the thoracic region, with relative sparing of the cervical and distal (lumbar) expansions.This was most marked at T4-7 levels, with associated subtle abnormal intramedullary T2 signal.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Hormonal testing at age 23 demonstrated a low estradiol level (29.7 pmol/L) with elevated LH (85.3 IU/L) and FSH (197.4 IU/L) levels, a profile consistent with ovarian insufficiency or post-menopausal state.

    “Hormonal testing at age 23 demonstrated a low estradiol level (29.7 pmol/L) with elevated LH (85.3 IU/L) and FSH (197.4IU/L) levels; a profile consistent with ovarian insufficiency or post-menopausal state.”
    Quote in the paperSubstantial claim

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

    Findingown data

    The patient developed a dystonic head tremor.

    “Additional neurologic examination features included impaired 2-point discrimination and proprioception in the feet, with a normal upper limb sensory examination, and a dystonic head tremor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Progressive exvacuo dilation of the lateral and third ventricles was demonstrated; third ventricular transverse distance was 6.7 mm at age 18 and 8.5 mm at age 27.

    “Progressive exvacuo dilation of the lateral (Figure 1) and third ventricles was demonstrated; third ventricular transverse distance (width) was 6.7 mm at age 18 and 8.5 mm at age 27”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The patient required a walker by 4 years, a wheelchair by 6 years, and by age 12 had no functional use of her lower limbs and developed joint contractures of the knees and ankles.

    “She required a walker by 4 years of age, and a wheelchair at 6 years.By age 12, she had no functional use of her lower limbs and developed joint contractures of the knees and ankles.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Chromosomal microarray demonstrated a normal female profile.

    “Chromosomal microarray demonstrated a normal female profile.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The patient developed progressive dysarthria from age three and dysphagia from age 10.

    “A progressive dysarthria developed from age three and was followed by dysphagia from age 10.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Serial MR imaging in this case demonstrated progressive white matter T2 hyperintensity and generalized atrophy on interval brain imaging.

    “Serial MR imaging in this case demonstrated progressive white matter T2 hyperintensity and generalized atrophy on interval brain imaging.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The case demonstrated previously unreported features of a dystonic head and neck tremor and primary ovarian failure.

    “Our case demonstrated the previously unreported features of a dystonic head and neck tremor and primary ovarian failure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MRI demonstrated progressive cord atrophy, supported on electrophysiological testing by loss of tibial SSEPs despite preserved peripheral nerve conduction studies.

    “In this case, MRI demonstrated progressive cord atrophy, although this is harder to display as a single image and is therefore not presented in the figures.This finding was supported on electrophysiological testing by loss of tibial SSEPs despite preserved peripheral nerve conduction studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Based on the findings of this case and the other reported adult case, progressive dysarthria, urinary dysfunction, and cognitive decline appear to develop as patients enter adulthood.

    “Based on the findings of our case and the other reported adult case, progressive dysarthria, urinary dysfunction, and cognitive decline appear to develop as patients enter adulthood.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bartlett et al., 2021 source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The superimposed episodes of reversible deterioration in this patient during fever are likely a consequence of further decompensation, in the setting of heightened stress placed on an already compromised cellular system.

    “The superimposed episodes of reversible deterioration in this patient during fever are likely a consequence of further decompensation, in the setting of heightened stress placed on an already compromised cellular system.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    In ACBD5-related retinal dystrophy with leukodystrophy, the earliest manifestations are generally nystagmus and retinal dystrophy, presenting within the first months of life.

    “In this condition, the earliest manifestations are generally nystagmus and retinal dystrophy, presenting within the first months of life.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    Prior cases of ACBD5-related retinal dystrophy with leukodystrophy have demonstrated an autosomal recessive pattern of inheritance.

    “Although prior cases of ACBD5-related retinal dystrophy with leukodystrophy have demonstrated an autosomal recessive pattern of inheritance”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The patient's premature ovarian insufficiency is suspected to be related to the peroxisomal disorder, with no alternative cause identified.

    “Our patient presented with premature ovarian insufficiency, which we suspect related to the peroxisomal disorder, with no alternative cause identified.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Diffuse white matter hypomyelination, leukodystrophy, and generalized atrophy are commonly reported imaging findings in ACBD5-related retinal dystrophy.

    “Diffuse white matter hypomyelination, leukodystrophy, and generalized atrophy are commonly reported imaging findings in ACBD5-related retinal dystrophy.”
    Quote in the paperNot a substantial claim
28 of 28

  • The paper relies on this without support.

    Plasma VLCFAs are typically abnormal in ACBD5-related retinal dystrophy with leukodystrophy.

    “Plasma VLCFAs are typically abnormal in ACBD5-related retinal dystrophy with leukodystrophy but were normal in our case.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Cognitive impairments in RDLKD typically emerge in childhood and appear to worsen during adolescence.

    “The cognitive impairments typically emerge in childhood and appear to worsen during adolescence (Rudaks et al., 2024).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Rudaks et al., 2024

    The Discussion (section 4; page unavailable) says cognitive decline appears to develop as patients enter adulthood, contrary to the claimed childhood onset and adolescent worsening. It describes childhood onset and teenage deterioration for motor symptoms, not cognition. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Cerebral atrophy with dilatation of the sulci and ventricles on MRI scans was observed in only two ACBD5-deficient patients.

    “However, cerebral atrophy—with dilatation of the sulci and ventricles on MRI scans—was observed in only two patients (Bartlett et al., 2021; Rudaks et al., 2024; Supplementary Table 1), indicating that widespread grey matter degeneration is potentially relatively rare.”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Rudaks et al., 2024

    The case description (section 1, page unavailable) reports progressive cerebral atrophy and dilation of the lateral and third ventricles in one patient. It does not report sulcal dilation or establish that only two ACBD5-deficient patients had this combination of MRI findings. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • MRI signal changes were detected in motor function-related gray matter structures, including the basal ganglia (three patients) and the red nucleus (two patients), in ACBD5 deficiency.

    “Notably, in addition to white matter abnormalities in the CNS, MRI signal changes were also detected in motor function-related gray matter structures, including the basal ganglia (three patients; Rudaks et al., 2024; Al Shamsi et al., 2025) and the red nucleus (two patients; Al Shamsi et al., 2025).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Rudaks et al., 2024

    The Investigations passage (indexed under Conclusion; page unavailable) reports increased T2 signal in cerebral white matter, including tracts of the basal ganglia, in one patient. It does not report signal changes in basal ganglia gray matter or findings in three patients. The red-nucleus finding is cited only to Al Shamsi et al., not to Rudaks et al. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Affective instability was reported in one ACBD5-deficient patient.

    “Additionally, affective instability was reported in one patient (Rudaks et al., 2024), suggesting a possible neuropsychiatric component to RDLKD—a feature that remains largely unexplored in peroxisomal disorders.”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Rudaks et al., 2024

  • Cognitive impairments were reported in six ACBD5-deficient patients.

    “Beyond motor and sensory deficits, cognitive impairments were reported in six patients (Ferdinandusse et al., 2017; Bartlett et al., 2021; Rudaks et al., 2024; Al Shamsi et al., 2025), and delayed language development in five (Ferdinandusse et al., 2017; Bartlett et al., 2021; Gorukmez et al., 2022; Hasturk et al., 2024; Al Shamsi et al., 2025; Supplementary Table 1).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Rudaks et al., 2024

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conclusion names a different gene

    Minor

    The conclusion calls the disorder ABCD5-related, while the title and case description identify it as ACBD5-related.

1 of 1

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Related

Authors
Rudaks, L. I., Triplett, J., Morris, K., Reddel, S., & Worgan, L.
Affiliations
The University of Sydney (AU)
Corresponding author
Rudaks, Laura Ivete
ORCID
Venue
American Journal of Medical Genetics Part A
Publisher
Wiley
Published
2023-10-03
Volume
194
Issue
2
Pages
346-350
ISSN
  • 1552-4825 (ISSN-L)
  • 1552-4833
DOI
10.1002/ajmg.a.63433
OpenAlex
W4387325970
Semantic Scholar
bb1937e463cc5240dd32bdd29312f4422c47dd97
Cited by
7
References
16
Citations by year
2025: 3 · 2024: 4
FWCI
0.53
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Medical Genetics Part A (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
University of Sydney
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
peroxisomal disorders, compound heterozygosity, novel mutations, retinal dystrophy, leukodystrophy, ataxia, spasticity, ovarian insufficiency, natural history (disease), disease progression
MeSH terms
Ataxia, Female, Humans, Membrane Proteins, Mutation, Pedigree, Phenotype, Primary Ovarian Insufficiency, Adaptor Proteins, Signal Transducing, Retinal Dystrophies

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