Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency
| Autor: | Susumu Ito, Aiko Nishikawa, Yuki Suzuki, Hirokazu Oguni, Yui Otani, Satoru Nagata, Keiichi Hara, Kaoru Eto |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Neutropenia Compound heterozygosity ACADS 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Internal medicine Medicine Beta oxidation chemistry.chemical_classification Valproic Acid business.industry Metabolic disorder Fatty acid General Medicine medicine.disease Endocrinology chemistry Pediatrics Perinatology and Child Health Toxicity lipids (amino acids peptides and proteins) Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Brain and Development. 43:657-660 |
| ISSN: | 0387-7604 |
| DOI: | 10.1016/j.braindev.2021.01.001 |
| Popis: | Background Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid β-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis. Case Report An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL). Furthermore, she presented with a high-grade fever with agranulocytosis (neutrophil 231/µL). The abnormal pharmacokinetics and toxicity of VPA raised the suspicion of possible inborn errors of metabolism in the fatty acid β-oxidation pathway. Blood tandem mass spectrometry revealed a transient elevation of C4, and urine gas chromatography-mass spectrometry revealed a continuous elevation of ethylmalonate. Finally, gene analysis revealed compound heterozygous mutations, c.625G > A (p.G209S) and c.1031A > G (p.E344G), in ACADS. Conclusion VPA should be avoided if a patient is suspected to have inborn errors of β-oxidation including SCAD deficiency. |
| Databáze: | OpenAIRE |
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