[Ring chromosome 20, hypersensitivity to valproate and hyperammonemic encephalopathy]

Area of Science:

• Neurology
• Clinical Genetics
• Pharmacology

Background:

• Ring chromosome 20 syndrome (C20A) is associated with intellectual disability, behavioral issues, dysmorphia, and difficult-to-treat epilepsy.
• Broad-spectrum antiepileptic drugs like valproate (VPA) and topiramate (TPM) are standard treatments.
• Literature review revealed no prior reports linking C20A with VPA hypersensitivity or hyperammonemic encephalopathy (HAE) from VPA and TPM combination therapy.

Observation:

• A 5-year-old patient with C20A presented with developmental delay, microcephaly, and refractory epilepsy.
• Treatment with VPA led to eosinophilia and rash, while adding TPM controlled seizures.
• The patient developed anorexia, weight loss, confusion, elevated eosinophils, and hyperammonemia, necessitating VPA discontinuation.

Findings:

• The patient exhibited hypersensitivity to VPA, evidenced by eosinophilia and rash.
• Combination therapy with VPA and TPM, though initially effective for seizures, resulted in hyperammonemic encephalopathy (HAE).
• Discontinuation of VPA was required due to hypersensitivity and HAE, despite TPM maintenance.

Implications:

• This case highlights potential VPA hypersensitivity and VPA-TPM combination-induced HAE in patients with C20A.
• Clinicians should monitor for these adverse effects in C20A patients treated with VPA and TPM.
• Further research is needed to understand the specific interactions between C20A, VPA, and TPM.