DeCure for Carnitine palmitoyltransferase II deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for carnitine palmitoyltransferase II deficiency — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCarnitine palmitoyltransferase II deficiency maps to a 4-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 palmitoyltransferase ii 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.
Molecular view
peroxisome proliferator activated receptor alpha (PPARA) — PPARA is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 1-methyl-3-oxo-3-phenyl-propylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1K7L · 2.5 Å · ligand 2-(1-METHYL-3-OXO-3-PHENYL-PROPYLAMINO)-3-{4-[2-(5-METHYL-2-PHENYL-OXAZOL-4-YL)-ETHOXY]-PHENYL}-PROPIONIC ACID (544). Experimental structure, not a prediction.
What the evidence adds up to
Seven patients with carnitine palmitoyltransferase II deficiency were studied on a triheptanoin diet providing 30% to 35% of total daily caloric intake for 7 to 61 months. Five had prior episodes of rhabdomyolysis requiring hospitalisation and muscle pain on exertion. On the diet, only two experienced mild muscle pain with exercise; none had rhabdomyolysis or hospitalisation. During short periods of noncompliance, two patients had rhabdomyolysis with exercise. Previously abnormal SF-36 physical composite scores returned to normal in all five symptomatic patients and exercise restriction was eliminated. The authors concluded the triheptanoin diet seemed effective for adult-onset CPT II deficiency.
A 2021 report from the Maritime Newborn Screening Program described a case of neonatal-onset CPT II deficiency identified through expanded newborn screening with tandem mass spectrometry. Early treatment interventions were initiated, metabolic decompensation was avoided, and the clinical outcome was described as better. The screening was reported as highly sensitive and specific with no false positives identified; the only screen positive case detected was a true positive. The authors argued for reconsideration of CPT II deficiency as a primary newborn screening target.
A 2021 study of six patients with carnitine palmitoyltransferase 1A deficiency (a different enzyme) reported that two were detected by neonatal screening and had no clinical symptoms, while four presented with seizures induced by fever, vomiting or diarrhoea. All six showed increased serum free carnitine, decreased hexadecanoylcarnitine and octadecanoylcarnitine, and increased C0/(C16+C18) ratio. Compound heterozygous CPT1A mutations were found in all six, including two reported and ten novel mutations. The authors noted that tandem mass spectrometry is helpful for early screening and diagnosis of CPT1A deficiency.
A 2025 case report described severe rhabdomyolysis in a 14-month-old infant with fever, hypotonia, and creatine phosphokinase levels above 100,000 UI/L. Primary metabolic analyses were normal. CPT II deficiency was diagnosed by genetic analysis, which identified a homozygous NM_000098.3, c.338C>T, p.[Ser113Leu] missense variant. The authors highlighted the difficulty of diagnosing CPT II deficiency in an infant and the importance of genetic analysis when acylcarnitine profiles are normal. What remains missing are controlled trials of triheptanoin versus standard dietary management, prospective data on newborn screening outcomes beyond single-centre reports, and validated biomarkers that reliably identify infantile cases before metabolic crisis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 95 citations · open access
Carnitine palmitoyltransferase II deficiency
AbstractBACKGROUND: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. METHODS: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. RESULTS: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. CONCLUSIONS: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency.
International Journal of Neonatal Screening · 2021 · 8 citations · open access
Detection of Early Onset Carnitine Palmitoyltransferase II Deficiency by Newborn Screening: Should CPT II Deficiency Be a Primary Disease Target?
AbstractEarly-onset carnitine palmitoyltransferase II deficiency (CPT II deficiency) (OMIM 600650) can result in severe outcomes, which are often fatal in the neonatal to infantile period. CPT II deficiency is a primary target in the Maritime Newborn Screening Program. We report a case of neonatal-onset CPT II deficiency identified through expanded newborn screening with tandem mass spectrometry. Identification through newborn screening led to early treatment interventions, avoidance of metabolic decompensation, and a better clinical outcome. Newborn screening for CPT II deficiency is highly sensitive and specific with no false positives identified. The only screen positive case detected identified a true positive case. This experience illustrates the importance of newborn screening for CPT II deficiency and demonstrates why reconsideration should be taken to add this disease as a primary newborn screening target.
[Clinical features and gene mutations of 6 patients with carnitine palmitoyltransferase 1A deficiency].
AbstractThe clinical and biochemical data and gene sequencing results of patients with carnitine palmitoyltransferase 1A deficiency were analyzed, in order to improve the understanding of the disease. Six patients (5 males and 1 female, aged from 1 to 8 years old) with carnitine palmitoyltransferase 1A deficiency from Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital between 2008 and 2019 were included. Two cases were detected by neonatal screening and had no clinical symptoms. The remaining 4 cases all showed seizures induced by fever, vomiting or diarrhea. All the 6 patients showed increased serum free carnitine (C0), decreased hexadecanoylcarnitine (C16) and octadecanoylcarnitine (C18), and increased C0/(C16+C18). Meanwhile, compound heterozygous mutations of CPT1A gene were detected in all 6 patients, of which 2 were reported mutations (c.281+1G>A and c.968-8C>T), and 10 were new mutations. The new mutations included 6 missense mutations, 1 nonsense mutation, 1 deletion mutation and 2 splicing mutations. Detection of free carnitine and acyl carnitine by tandem mass spectrometry is helpful for early screening and diagnosis of carnitine palmitoyltransferase 1A deficiency.
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.
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.
