Whole genome sequencing (WGS) and genome joint analysis represent a paradigm shift in genetic diagnostics, offering an unparalleled ability to uncover the molecular basis of disease. These innovative, cutting-edge technologies are hailed as first-line diagnostic tools and are particularly critical for patients who remain undiagnosed following exhaustion of conventional medical approaches. Genome joint analysis serves as a biointelligent solution to pinpoint elusive genetic variants, enabling earlier and more precise intervention. Our patient was enrolled in the CROseq Genome Program after traditional diagnostic methods failed to uncover the underlying cause of disease. Joint analysis detected a novel likely pathogenic variant in the ABCD1 gene in the child. Although he remains in the pre-symptomatic stage, he is currently at the age of highest risk for developing cerebral drenoleukodystrophy (CALD). In the absence of timely intervention, CALD rapidly progresses to total disability, followed by death, shortly after symptom onset. Early diagnosis is therefore of crucial importance, as hematopoietic stem cell transplantation (HSCT) and ex vivo gene therapy can positively alter the disease trajectory and significantly improve patient outcomes when initiated during the pre-symptomatic stage. Establishing the diagnosis during this critical window, however, can be challenging. The biochemical marker, elevated very long-chain fatty acids (VLCFA), is a non-specific finding shared with other disorders of peroxisomal biogenesis. Additionally, the clinical course is complicated by the heterogeneity of clinical manifestations and the potential for cerebral involvement to begin at any age. In this context, genome joint analysis emerges as a powerful tool, enabling the rapid and precise identification of pathogenic ABCD1 variants and thereby guiding the timely implementation of targeted, life-saving therapies. This review, together with the case presentation, aims to provide a comprehensive overview of drenoleukodystrophy and highlight the clinical relevance and actionable therapeutic potential of genome joint analysis. The unpredictable clinical course and rapid deterioration observed in CALD underscores the significance of genome joint analysis in providing a comprehensive genetic profile that facilitates the implementation of personalized care for a rare disease with a narrow therapeutic window.