DeCure for Alpha-methylacyl-CoA racemase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Alpha-methylacyl-CoA racemase deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAlpha-methylacyl-CoA racemase deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for alpha-methylacyl-coa racemase deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder that leads to accumulation of pristanic acid, dihydroxycholestanoic acid, and trihydroxycholestanoic acid. The 2024 report of four patients from two families describes a 10-month-old female who presented with coagulopathy, hepatic dysfunction, and elevated pristanic acid, DHCA, and THCA levels, with a homozygous c.596G>A variant in the AMACR gene. Her brother was diagnosed through family screening and had macrovesicular hepatosteatosis and elevated pristanic acid. A third patient presented with rhabdomyolysis after strenuous exercise and carried a novel homozygous c.1006G>A variant; his asymptomatic sister with the same variant also had elevated pristanic acid. Both sibling pairs had normal neuropsychologic evaluation. Dietary treatment with low phytanic and pristanic acid content was recommended but all patients showed poor compliance. The sibling pairs were followed for 11 and 7 years respectively.
The 2007 case describes a patient with relapsing encephalopathy, seizures, and cognitive decline over 40 years, with grossly elevated plasma pristanic acid and deficient AMACR in skin fibroblasts due to a homozygous c.154T>C mutation. The 2012 report describes an incidental presymptomatic diagnosis of AMACR deficiency in a boy with oculocutaneous albinism type 4, identified through genome-wide studies that found a homozygous deletion on chromosome 5p13.3 encompassing the SLC45A2 gene and four additional genes. The 2023 reader response notes that whole-genome sequencing in 242 adult patients with suspected mitochondrial disorders identified three patients from two families with adult-onset AMACR deficiency, and that the condition was found in three families in the 100,000 Genomes Project and one patient in a whole-exome sequencing study.
The clinical phenotypes are variable, with age of onset from infancy to late adulthood, and the disorder is usually described as adult-onset with neuropsychological problems. No controlled treatment trials exist. The 2024 report notes that dietary treatment was recommended but compliance was poor, and the natural history and new clinical phenotypes remain incompletely characterised. What is still missing are prospective natural history studies, reliable biomarkers for disease progression, and any randomised trial of dietary or other interventions. Patient stratification by age of onset, presenting symptoms, and genotype is not yet possible given the small number of reported cases.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Relapsing encephalopathy in a patient with -methylacyl-CoA racemase deficiency
AbstractAlpha-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.
American Journal of Medical Genetics Part A · 2012 · 14 citations
Incidental finding of alpha‐methylacyl‐CoA racemase deficiency in a patient with oculocutaneous albinism type 4
AbstractGenome-wide studies may lead to the discovery of genetic variants of potential clinical importance beyond the aims of the study. We performed single nucleotide polymorphism array analysis in a boy with oculocutaneous albinism to identify copy-neutral regions of homozygosity harboring genes involved in melanin biosynthesis. An unanticipated homozygous deletion of chromosome 5p13.3 was discovered, encompassing not only the OCA gene SLC45A2, but also four additional genes. This led to an unexpected presymptomatic diagnosis of alpha-methylacyl-CoA racemase deficiency in the same patient.
Variable clinical phenotypes of alpha‐methylacyl‐<scp>CoA</scp> racemase deficiency: Report of four cases and review of the literature
AbstractAbstract Alpha‐methylacyl‐ CoA ‐racemase ( AMACR ) deficiency ( MIM #604489) is a peroxisomal disorder resulting in the accumulation of pristanic acid, dihydroxycholestanoic acid ( DHCA ), and trihydroxycholestanoic acid ( THCA ), with variable clinical features and age of onset from infancy to late adulthood. The purpose of this report is to define clinical variations and follow‐up data in AMACR deficiency emphasizing treatment with a review of cases reported in the literature. Here, four patients, from two families, diagnosed with AMACR deficiency and showing phenotypic heterogeneity are presented. A 10‐month‐old‐female presented with coagulopathy, hepatic dysfunction, and elevated pristanic acid, DHCA, and THCA levels. Genetic testing confirmed a homozygous variant c. 596G >A in the AMACR gene. Her brother who had macrovesicular hepatosteatosis and elevated pristanic acid levels was diagnosed with family screening. The third patient presented with rhabdomyolysis following a strenuous exercise without any other complaint. Homozygous novel c. 1006G >A variant was found on the AMACR gene. His asymptomatic sister carrying the same variant also had elevated pristanic acid levels. They had normal neuropsychologic evaluation. Dietary treatment with low phytanic and pristanic acid content was recommended to the patients but all showed poor compliance. The sibling pairs were followed for periods of 11 and 7 years, respectively. AMACR deficiency is usually described as an adult‐onset disorder with neuropsychological problems. The characterization of natural history and new clinical phenotypes may support earlier diagnosis and treatment.
Apollo (University of Cambridge) · 2023 · 0 citations · open access
Reader Response: Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.
AbstractWe were interested to read this study, in which the authors applied a “genomics first” approach in 242 adult patients.1 They identified 3 patients from 2 families with an adult-onset peroxisomal disorder, alpha-methylacyl-CoA racemase deficiency. This condition was identified in 3 families with suspected mitochondrial disorders in the 100,000 Genomes Project and 1 patient in the whole-exome sequencing study by Theunissen et al.2,3
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
