DeCure for Carnitine-acylcarnitine translocase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for carnitine-acylcarnitine translocase 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 moduleCarnitine-acylcarnitine translocase 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 carnitine-acylcarnitine translocase 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
A 2003 report on a single patient with carnitine-acylcarnitine translocase deficiency described a novel Q238R missense mutation. The infant presented shortly after birth with cardiac myopathy, arrhythmia, and severe non-ketotic hypoglycaemia. Treatment with a medium-chain triglyceride formula and carnitine supplementation reduced long-chain acylcarnitine concentrations and reversed the cardiac symptoms and hypoglycaemia. The authors suggested that this combination may be effective for this defect of long-chain fatty acid oxidation.
A 2010 case series of three Saudi siblings with a severe phenotype reported that early medical intervention with 25% dextrose infusion, carnitine, and a high-carbohydrate low-fat formula produced a good clinical and biochemical response in one patient. However, early nephrocalcinosis, severe hypotonia, and an intravascular cerebral accident could not be prevented, and the child died at 18 months from metabolic decompensation. The authors concluded that CACT deficiency remains lethal even with early and aggressive medical intervention.
A 2022 analysis of 78 previously identified patients, including a new Chinese neonatal case homozygous for the c.199–10T>G variant who died three days after delivery, found that this variant accounted for 82.6% of alleles in Chinese patients. Among 30 patients with the c.199–10T>G mutation, 22 carried the splicing variation. A 2023 report on Filipino twins described compound heterozygous variants (M1:c.706_707insT and M2:c.689C>G) and noted that both infants died between 1.5 and 3.5 days of age. A 2025 case of severe rhabdomyolysis in a 14-month-old infant was ultimately diagnosed as carnitine palmitoyltransferase II deficiency, not CACT deficiency, after genetic analysis identified a homozygous S113L missense variant; the acylcarnitine profile had been normal.
Across these reports, the prognosis for CACT deficiency remains poor even with early treatment. No controlled trial has been conducted. What is still missing is a systematic, prospective study with sufficient patient numbers to test whether any intervention changes survival, and a reliable method to stratify patients by genotype or residual enzyme activity before birth.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2003 · 46 citations · open access
Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation
AbstractDeficiency of carnitine/acylcarnitine translocase (CACT) is an autosomal recessive disorder of the carnitine cycle resulting in the inability to transfer fatty acids across the inner mitochondrial membrane. Only a limited number of affected patients have been reported and the effect of therapy on this condition is still not well defined. Here, we report a new patient with this disorder and follow the response to therapy. Our patient was the product of a consanguineous marriage. He presented shortly after birth with cardiac myopathy and arrhythmia coupled with severe non-ketotic hypoglycemia. Initial metabolic studies indicated severe non-ketotic C6-C10 dicarboxylic aciduria, plasma carnitine deficiency, and a characteristic elevation of plasma C:16:0, C18:1, and C18:2 acylcarnitine species. Enzyme assay confirmed deficiency of CACT activity. Molecular studies indicated that this child was homozygous, and both parents heterozygous, for a single bp change converting glutamine 238 to arginine (Q238R). Therapy with a formula providing most of the fat via medium chain triglycerides (MCT) and carnitine supplementation reduced the concentration of long-chain acylcarnitines and reversed cardiac symptoms and the hypoglycemia. These results suggest that carnitine and MCT may be effective in treating this defect of long-chain fatty acid oxidation.
Carnitine-acylcarnitine translocase deficiency. Clinical course of three Saudi children with a severe phenotype
AbstractCarnitine-acylcarnitine translocase (CACT) deficiency (McKusick 212138) is a rare life threatening disorder characterized by hypoketotic hypoglycemia, hyperammonemia, encephalopathy, cardiomyopathy hepatopathy, and myopathy. Here, we present a detailed clinical course of 3 Saudi siblings with a severe phenotype. The third patient was described in more detail. Early medical intervention in the form of 25% dextrose intravenous infusion and carnitine supplement followed by a gradual introduction of a high carbohydrate low fat special formula resulted in a good clinical and biochemical response to the treatment in our patient. However, early nephrocalcinosis, severe hypotonia, and subsequently intravascular cerebral accident could not be prevented. He died at 18 months of age as a result of metabolic decompensation. This suggests that CACT deficiency is still a lethal disorder even with an early and aggressive medical intervention.
Frontiers in Pediatrics · 2022 · 6 citations · open access
One potential hotspot SLC25A20 gene variants in Chinese patients with carnitine-acylcarnitine translocase deficiency
AbstractBackground Carnitine-acylcarnitine translocase deficiency (CACT deficiency) is a rare and life-threatening autosomal recessive disorder of mitochondrial fatty acid oxidation caused by variant of SLC25A20 gene. The most prevalent missense variant in the SLC25A20 gene in Asia was c.199–10T > G. Due to the c.199–10T > G variant, CACT deficiency is a severe phenotype. Materials and Methods Herein, we present a neonatal case with c.199–10T > G variant in China and analyze the clinical, biochemical, and genetic aspects of 78 patients previously identified with CACT deficiency. Results The patient presented with a series of severe metabolic crises that rapidly deteriorated and eventually died 3 days after delivery. The sequencing of the patient's genome indicated that he was homozygous for the c.199–10T > G variant. 30 patients were found to have the c.199–10T > G mutation, of which 23 were Chinese and 22 were afflicted by the c.199–10T > G splicing variation. In China, c.199–10T > G allele frequency was 82.6%. Conclusion In CACT deficiency, prompt recognition and treatment are critical. Our data suggested that c.199–10T > G may be a potential hotspot SLC25A20 gene mutation in the Chinese population. Detection of single nucleotide polymorphism is possible for high-risk patients and parents in China.
Journal of International Medical Research · 2023 · 5 citations · open access
Carnitine-acylcarnitine translocase deficiency caused by <i>SLC25A20</i> gene heterozygous variants in twins: a case report
AbstractThe current case report describes the clinical, biochemical and genetic characteristics of carnitine-acylcarnitine translocase deficiency (CACTD) in infant male and female twins that presented with symptoms shortly after elective caesarean delivery. The clinical manifestations were neonatal hypoglycaemia, arrhythmia and sudden death. The age of onset was 1.5 days and the age of the death was 1.5–3.5 days. Dried blood filter paper analysis was used for the detection of acylcarnitine. Peripheral venous blood and skin samples were used for next-generation sequencing. The twins and their parents underwent gene analysis and whole exome sequencing analyses of the solute carrier family 25 member 20 ( SLC25A20; also known as carnitine-acylcarnitine translocase) gene. Both infants carried compound heterozygous variants of the SLC25A20 gene: variant M1:c.706_707insT:p.R236L fs*12 and variant M2:c.689C>G:p.P230R. The M1 variant was paternal and had not been previously reported regarding CACTD. The M2 variant was maternal. CACTD has severe clinical manifestations and a poor prognosis, which is manifested as hypoketotic hypoglycaemia, hyperammonaemia, liver function damage and elevated creatine kinase.
International Journal of Neonatal Screening · 2023 · 2 citations · open access
Carnitine-acylcarnitine Translocase Deficiency with c.199-10T>G Mutation in Two Filipino Neonates Detected through Parental Carrier Testing
AbstractCarnitine-acylcarnitine translocase deficiency (CACTD), a fatty acid oxidation defect (FAOD), can present in the neonatal period with non-specific findings and hypoglycemia. A high index of suspicion is needed to recognize the disorder. The case is of a 24-year-old G2P2(2000) mother who sought consultation for recurrent neonatal deaths. The neonates, born two years apart, were apparently well at birth but had a fair cry and no spontaneous eye opening within the first 24 h of life and died before the 72nd hour of life. Newborn screening of both babies revealed elevated long chain acylcarnitines and hypocarnitinemia suggestive of a FAOD. However, due to their early demise, no confirmatory tests were done. Parental carrier testing was performed, revealing both parents to be heterozygous carriers of a pathogenic variant, c.199 10T>G (intronic), in the SLC25A20 gene associated with autosomal recessive CACTD. This is the first reported case of CACTD in the Filipino population.
Journal of Medical Case Reports · 2025 · 0 citations · open access
Severe rhabdomyolysis in an infant due to fatty acid oxidation disorder: a case report
AbstractBACKGROUND: Rhabdomyolysis can develop from numerous etiologies, both acquired and hereditary. Consequences of rhabdomyolysis may be grave, therefore identifying and treating the etiology is crucial. CASE PRESENTATION: We herein report the occurrence of severe rhabdomyolysis in a previously healthy 14-month-old infant presenting to the emergency department with fever, hypotonia, and generalized discomfort. Analysis revealed extremely high creatine phosphokinase levels (> 100,000 UI/L). Metabolic myopathy was suspected, however, primary metabolic analyses were normal. Carnitine palmitoyltransferase II deficiency was diagnosed following genetic analysis, identifying a homozygous NM_000098.3, c.338C > T, p.[Ser113Leu] missense variant. Prophylactic measures were established to prevent relapse and genetic counseling provided for the sibship. CONCLUSION: This case highlights the difficulty of diagnosing carnitine palmitoyltransferase II deficiency in an infant and the importance of genetic analysis to establish the diagnosis, despite a normal acylcarnitine profile.
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.
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