Diagnostic Odyssey of a Rare Disease in a Pediatric Rehabilitation Program: The Longest-Living Reported Case of Ethylmalonic Encephalopathy

Abstract

Introduction:
Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder caused by mitochondrial dysfunction and accumulation of hydrogen sulfide and toxic metabolites. Clinical features include global developmental delay, seizures, hypotonia, and multisystem involvement that may mimic cerebral palsy, leading to delayed diagnosis.

Objective:
To present a clinical case of EE, emphasizing diagnostic challenges, therapeutic strategies, and the critical role of multidisciplinary rehabilitation.

Case report:
A 25-year-old male was initially diagnosed with spastic cerebral palsy and moderate intellectual disability. He exhibited chronic diarrhea, petechiae, acrocyanosis, spasticity, intestinal polyposis, and neurogenic bladder. After multiple evaluations, EE was confirmed at age 22 by genetic sequencing (ETHE1 c.488G>A, homozygous). Although specific pharmacological therapy began late, the patient achieved the longest survival ever reported, primarily due to long-term family support and an intensive pediatric rehabilitation program spanning nearly two decades.

Results:
Published literature reports a maximum survival of approximately 11 years in most EE cases. This report documents the oldest patient with EE, highlighting the decisive impact of rehabilitation and sustained supportive care.

Conclusions:
EE should be considered in the differential diagnosis of atypical cerebral palsy, particularly when chronic diarrhea, acrocyanosis, or hemorrhagic manifestations are present. This case emphasizes the essential role of multidisciplinary rehabilitation and chronic care in improving quality of life and extending survival in individuals with disability due to rare metabolic disorders.