Authors :
Presenting Author: Sofia Mirshed, MBA, CCRP – Ann & Robert H. Lurie Children's Hospital of Chicago
Enrique Rojas, CCRC – Ann and Robert H Lurie Children's Hospital of Chicago
Megan Keeler, M Ed, MPH, MSW, LSW – Ann & Robert H. Lurie Children's Hospital of Chicago
Marija Stosic, MD, MBA – Ann & Robert H. Lurie Children's Hospital of Chicago
Linda Laux, M.D. – Ann & Robert H. Lurie Children's Hospital of Chicago
Priyamvada Tatachar, MBBS, MD – Ann & Robert H. Lurie Children’s Hospital of Chicago
Rationale:
Menkes disease (MD) is a rare X-linked neurodegenerative disorder caused by ATP7A mutations, leading to copper deficiency and impaired function of copper-dependent enzymes. Clinical features emerge in infancy and include developmental regression, connective tissue abnormalities, coarse hair, and epilepsy. Seizures often present at 2–3 months and evolve (Verrotti et al., 2014). Focal seizures can precede infantile spasms and progress to epileptic encephalopathy or Lennox-Gastaut Syndrome with tonic, myoclonic, atypical absence seizures, and epileptic spasms. Without treatment, classic MD is often fatal by age 3. Copper histidinate (CuHis) is an investigational therapy designed to restore copper homeostasis, most effective when started early in patients with residual ATP7A function (Kaler, 2011). This review describes diagnostic features and clinical outcomes of MD patients treated under an Expanded Access Program (EAP) at our center.Methods:
We performed a retrospective review of 4 patients with genetically confirmed MD treated with subcutaneous CuHis from 2019-2025. Data included demographics, mutation type, initial copper studies, clinical features, treatment regimen, and developmental, neurologic, and safety domain outcomes.Results:
Median age at diagnosis was 6 months; median age at treatment initiation was 6.5 months. All patients had pathogenic ATP7A mutations; 1 de novo, 3 maternally inherited. No affected siblings were identified; 1 female sibling was a carrier. 3/4 presented with seizures before MD diagnosis, treated with different anti-seizure medications (ASMs). Baseline copper and ceruloplasmin levels were low. CuHis was dosed 250mcg twice daily until 1 year of age, then once daily for up to 3 years total treatment. Adherence was generally high. Of the 4 patients enrolled, 1/4 currently on therapy, 2/4 discontinued 3–6 months prior to end of treatment for concern of treatment effects, and 1/4 died at age 4.
Treatment responses included improved tone, alertness, hair/skin texture, motor and cognitive gains. Seizures stabilized and improved, leading to ASM weaning. EEG findings were variable; background appeared to improve and stabilize. All patients were enrolled in therapies and needed G-tube feeds. Multidisciplinary care involved nephrology, gastroenterology, pulmonology, and urology; 2/4 received palliative care. No hepatic or renal toxicity related to CuHis was observed. 1/4 developed anasarca and hypoalbuminemia; causality was unclear.Conclusions:
MD is a progressive neurodegenerative disorder with dismal prognosis. Parenteral CuHis under an EAP showed a favorable safety profile and signs of clinical stabilization and neurocognitive benefit in our cohort. Early treatment, ideally in the neonatal period, even before seizure onset, is associated with improved outcomes. High index of suspicion in infants with early focal epilepsy or infantile spasms with typical clinical features should prompt early testing and initiation of treatment with multidisciplinary intervention.Funding: No direct funding was provided for this abstract.