Background <p>Angelman Syndrome (AS) is a rare neurogenetic disorder characterized by developmental delay, seizures, and a distinctive behavioral profile including frequent laughter and hyperactivity. Although neurological symptoms are typically emphasized, gastrointestinal complications are also common and may significantly affect quality of life. This case report is noteworthy due to the observed relationship between liver enzyme levels, dietary protein intake, and antiseizure medications dosage in a child with Angelman Syndrome with accompanying epilepsy (which affects about 90% of AS patients) (Seizure 17:211, 2008). It illustrates how detailed home-based monitoring and interdisciplinary care can lead to clinically meaningful improvements.</p> Case presentation <p>We present the case of a nine-year-old girl with genetically confirmed Angelman syndrome. The diagnosis was first suggested by next-generation sequencing (NGS) in 2021, which identified two heterozygous variants: UBE3A: c.1432A &gt; G (p.Met498Val), classified as likely pathogenic, and SCN1A: c.4713A &gt; T, classified as likely benign. One year later, array-CGH confirmed a typical, non-mosaic maternal 15q11–q13 microdeletion (canonical type I), recognized as the primary pathogenic mechanism of Angelman syndrome in this patient. This deletion also provides the most plausible explanation for the occurrence of epilepsy, which is common in Angelman syndrome, rather than the benign SCN1A variant. A segregation analysis to determine the parental origin of the UBE3A variant is planned but has not yet been completed due to the unavailability of paternal DNA.</p> <p>Since infancy, the patient exhibited chronic gastrointestinal symptoms, including gastroesophageal reflux, feeding difficulties, and persistent elevation of liver enzymes, particularly alanine transaminase (ALT). Epilepsy has been treated with long-term antiseizure medications, which contributed to hepatic enzyme abnormalities. Serial monitoring revealed that ALT fluctuations correlated with both dietary composition and medication dosing: higher levels were observed with high animal protein and saturated fat intake combined with full-dose antiseizure therapy, whereas lower levels occurred with reduced animal protein, increased unsaturated fat consumption, and medication dose adjustment under medical supervision. Regular physical activity also appeared to exert a beneficial effect. Imaging and laboratory investigations excluded infectious, autoimmune, and structural liver disease, and no signs of liver failure were detected. Over time, enzyme levels decreased following integrated dietary and pharmacological modifications.</p> Conclusions <p>This case highlights the multifactorial nature of gastrointestinal and hepatic symptoms in children with Angelman Syndrome with accompanying epilepsy. It underscores the importance of individualized care that integrates neurology, gastroenterology, nutrition, and physical therapy. The observed improvements following tailored interventions suggest that liver function abnormalities in such patients may be modifiable through careful management of diet and medication dose. Additionally, the case demonstrates the valuable role of caregiver-led observation in chronic disease management. This report supports a broader, systemic approach to care for children with complex neurodevelopmental conditions, encouraging proactive monitoring and collaboration among healthcare providers and families.</p>