DeCure for Carnitine palmitoyl transferase 1A deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for carnitine palmitoyl transferase 1A 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 palmitoyl transferase 1A 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 palmitoyl transferase 1a 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 1981 study of a 13-year-old boy with exertion-induced cramps and myoglobinuria found that mitochondrial preparations from his skeletal muscle were deficient in carnitine palmitoyltransferase (CPT) activity by hydroxamate and kinetic assays. His fibroblasts were also deficient by those assays but not by the DTNB method, which the authors interpreted as a specific deficiency of one of the two CPT enzymes, presumably CPT II. A 2025 case report describes a 14-month-old infant with fever, hypotonia, and severe rhabdomyolysis (creatine phosphokinase >100,000 UI/L) whose acylcarnitine profile was normal but who was diagnosed with CPT II deficiency by genetic analysis, which found a homozygous NM_000098.3, c.338C>T, p.[Ser113Leu] missense variant. The authors note the diagnostic difficulty and the importance of genetic testing when the acylcarnitine profile is unremarkable.
A 2021 report from the Maritime Newborn Screening Program describes neonatal-onset CPT II deficiency as often fatal in the neonatal to infantile period. The program identified one true positive case with no false positives, and early treatment after newborn screening led to avoidance of metabolic decompensation and a better clinical outcome. The authors argue that CPT II deficiency should be reconsidered as a primary newborn screening target.
A 2021 study of six patients (five male, one female, aged 1 to 8 years) with CPT1A deficiency found that two were detected by newborn screening and were asymptomatic, while the other four presented with seizures induced by fever, vomiting, or diarrhoea. All six had increased serum free carnitine (C0), decreased hexadecanoylcarnitine (C16) and octadecanoylcarnitine (C18), and an increased C0/(C16+C18) ratio. Compound heterozygous CPT1A mutations were found in all six; two were previously reported and ten were new. A 2018 case series of three patients with CPT1 deficiency describes a range of presentations including cardiac complications, increasing lethargy during intercurrent illness, and seizures with severe metabolic acidosis, calling the clinical picture a "camouflage" of contrasting manifestations.
What is still missing is prospective data on whether newborn screening for CPT II or CPT1A deficiency reduces mortality or long-term disability in a general population, and whether the early treatment interventions used in the Maritime programme are standardised or reproducible elsewhere. No randomised trial has compared screening versus clinical detection for either deficiency. The 2025 case also shows that a normal acylcarnitine profile does not rule out CPT II deficiency, meaning reliance on biochemical screening alone will miss some cases. Patient stratification by genotype, age at onset, and tissue-specific isoform expression remains poorly defined, and no therapy beyond supportive management and avoidance of fasting has been tested in a controlled setting.
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.
Selective carnitine palmitoyltransferase deficiency in fibroblasts from a patient with muscle CPT deficiency
AbstractA 13-year-old boy developed cramps and myoglobinuria following exertion. Mitochondrial preparations from a skeletal muscle biopsy were deficient in carnitine palmitoyltransferase (CPT) activity when assayed by the hydroxamate and kinetic assays. The patient's fibroblasts were also deficient when assayed by the hydroxamate and kinetic assays, but not when tested by the DTNB (5,5'-dithiobis-[nitrobenzoic acid]) method. This disparity probably indicates a specific deficiency in fibroblasts of one of the two carnitine palmitoyltransferases, presumably CPT II.
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 CLINICAL AND DIAGNOSTIC RESEARCH · 2018 · 1 citations · open access
A Clinical and Biochemical Camouflage-Carnitine Palmitoyltransferase-1 Deficiency: A Case Series
AbstractCarnitine Palmitoyltransferase-1 (CPT-1) deficiency is a rare metabolic disorder of fatty acid oxidation. The presentation of this deficiency is a mixed bag of several clinical and biochemical manifestations which is determined by the tissue-specific isoforms of the enzyme. Presenting in one way, which can be lethal due to cardiac complications, another way that this disorder can come to a clinician’s attention is when children manifests with increasing lethargy during intercurrent illnesses. Rarely, but not exclusively, a seizure may be the only presenting complaint along with severe metabolic acidosis. In this case series, we present a discussion of three cases with CPT1 deficiency presenting with a camouflage of various contrasting clinical and biochemical manifestations.
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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