Disease spectrum and genetic profile of high-risk children with severe carnitine deficiency.

Background

Severe free carnitine deficiency (C0 ≤5 μmol/L) is frequently observed in pediatric patients suspected of primary carnitine deficiency (PCD), though confirmed diagnoses remain rare. This study aimed to analyze the disease spectrum and genetic profile of high-risk children with severe reduced carnitine levels and to enable targeted treatment.

Methods

We retrospectively analyzed blood acylcarnitine profiles (ACP), urine organic acids, genetic results, and clinical features of high-risk pediatric patients with significantly low C0 levels, which led to a diagnosis.

Results

Among 56 high-risk patients with C0 levels below 5 μmol/L, 19 were diagnosed with inherited metabolic diseases (IMD): 7 cases of PCD and 12 other metabolic disorders. Three novel genetic variants across three genes were identified, which had not been previously reported. Notably, one patient with PCD also had methylmalonic acidemia, and three IMD patients exhibited characteristic metabolic markers of their conditions only after levocarnitine supplementation. Among the 37 non-IMD cases, critical condition with perinatal multi-organ dysfunction and refractory epilepsy or diarrhea-associated convulsions were the predominant etiologies.

Conclusion

Severe C0 deficiency in high-risk children is primarily caused by non-genetic factors. Additionally, in some non-PCD fatty acid oxidation disorders, extremely low free carnitine levels may mask primary disease markers, increasing the risk of misdiagnosis. Timely follow-up blood ACP after l-carnitine supplementation, combined with urinary organic acid analysis and genetic testing, is crucial for early diagnosis and therapeutic monitoring.