In the realm of psychiatric diagnostics, the journey to a definitive diagnosis can often be labyrinthine, fraught with overlapping symptoms and confounding factors. A recent case report published in BMC Psychiatry illustrates this complexity through the lens of a young female patient whose symptoms initially pointed toward Attention Deficit Hyperactivity Disorder (ADHD) but who ultimately revealed a far more intricate medical reality. This story underscores the critical importance of comprehensive diagnostic workups, especially in cases where metabolic disorders may masquerade as more common psychiatric conditions.
ADHD is widely recognized as a prevalent neurodevelopmental disorder characterized by symptoms such as inattentiveness, hyperactivity, and impulsivity. However, these symptoms are not exclusive to ADHD and can be mimicked or exacerbated by other conditions, including substance use disorders like alcohol or illicit drug addiction. The clinical challenge lies in teasing apart these overlapping presentations to avoid misdiagnosis and ensure appropriate treatment. The presented case sharply highlights this diagnostic dilemma.
At the outset, the patient’s clinical presentation was consistent with classic ADHD symptoms. Yet, a standard laboratory investigation threw a curveball: the patient exhibited an alarmingly high carbohydrate-deficient transferrin (CDT) level of 19.6%, which far exceeds the typical threshold of less than 1.3%. CDT is a biomarker commonly used to detect chronic alcohol abuse because excessive alcohol consumption disrupts protein glycosylation, resulting in abnormal transferrin isoforms. Elevated CDT in this context typically signals alcohol addiction, which can produce symptoms similar to ADHD.
Despite the strong indication of alcohol misuse suggested by the CDT levels, a rigorous diagnostic evaluation unequivocally ruled out alcohol addiction. This paradox prompted clinicians to delve deeper into alternative explanations. Further biochemical analysis revealed the presence of a congenital disorder of glycosylation (CDG)—a rare, inherited metabolic condition that impairs the normal enzymatic processes responsible for attaching sugar molecules (glycans) to proteins and lipids. Glycosylation is a vital post-translational modification affecting protein folding, stability, and function. Aberrations in this process can profoundly affect multiple organ systems, including the central nervous system, thereby manifesting with diverse neuropsychiatric symptoms.
This case exemplifies the fact that elevated CDT can have etiologies beyond alcohol misuse. Specifically, a transferrin mutation affecting glycosylation sites was identified as the culprit behind the deceptive laboratory findings. Such mutations are not only rare but typically evade straightforward clinical suspicion, reinforcing the necessity for metabolic screening in patients with atypical lab results combined with neuropsychiatric manifestations. The identification of CDG in this patient ultimately reframed the clinical understanding of her symptoms.
Psychiatric symptoms associated with metabolic disorders like CDG present a diagnostic challenge because they overlap significantly with common psychiatric conditions such as ADHD. This convergence demands that clinicians maintain a high index of suspicion for underlying organic causes in atypical or treatment-resistant cases. Moreover, it highlights the interconnectivity between psychiatry and metabolic medicine, advocating for multidisciplinary approaches in complex cases.
Substance-use disorders (SUD) also loom large in the differential diagnostic landscape for ADHD, given the high degree of symptom overlap and frequent comorbidity. Withdrawal syndromes, intoxication effects, and chronic substance-induced neurobiological changes can all mimic or worsen ADHD-like symptoms. Therefore, distinguishing primary ADHD from secondary symptoms associated with substance use is crucial, as it dramatically impacts therapeutic decisions and long-term management strategies.
In this compelling narrative, the clinical team’s perseverance in conducting extensive metabolic and genetic evaluations thwarted a potentially misleading diagnosis of alcohol addiction. Such diligence ensured that the patient’s metabolic disorder was recognized as the root cause of her symptoms. This not only redirected the treatment focus but also served as a cautionary tale for clinicians worldwide regarding the limitations of relying solely on standard psychiatric assessments and common biomarkers.
The molecular intricacies of CDG, involving disruptions in glycoprotein biosynthesis pathways, underscore how fundamental cellular processes, when aberrant, can manifest as complex clinical syndromes. Transferrin, a glycoprotein critical for iron transport, becomes a key diagnostic marker under such conditions. Abnormal electrophoretic patterns of transferrin isoforms, including carbohydrate-deficient forms, thereby emerge as hallmarks of glycosylation defects, making precise laboratory interpretation essential.
Furthermore, this case reaffirms the growing recognition that metabolic disorders can and do substantially contribute to neuropsychiatric phenomena. Advances in metabolic screening technologies and increased clinical awareness are gradually bridging the gap between neurology, psychiatry, and genetics, facilitating earlier and more accurate diagnoses. Early recognition of metabolic etiologies can prevent misdiagnosis, reduce unnecessary treatments, and ultimately improve patient outcomes.
In conclusion, this detailed case report serves as a testament to diagnostic vigilance and the importance of considering rare metabolic diseases such as CDG in psychiatric differential diagnoses. For patients presenting with ADHD-like symptoms alongside abnormal laboratory markers, clinicians must contemplate broader etiologic possibilities beyond common psychiatric explanations or substance use. Such an integrative approach ensures precision medicine prevails, tailoring therapies to the genuine underlying pathophysiology.
This report, published in BMC Psychiatry volume 25, article number 435 in 2025, not only expands the clinical understanding of ADHD-like presentations but also stresses the imperative for collaborative, multidisciplinary diagnostics. As psychiatric and metabolic sciences continue to intersect, cases like these illuminate pathways toward improved clinical paradigms, ultimately fostering better patient care.
Subject of Research: Diagnostic complexities differentiating ADHD, alcohol addiction, and congenital disorder of glycosylation (CDG) in psychiatric presentations.
Article Title: The long way to diagnosis: attention disorder, alcohol addiction or congenital disorder of glycosylation? A case report
Article References:
Faustmann, T.J., Hensel, L., Bahic, A. et al. The long way to diagnosis: attention disorder, alcohol addiction or congenital disorder of glycosylation? A case report. BMC Psychiatry 25, 435 (2025). https://doi.org/10.1186/s12888-025-06862-9
Image Credits: AI Generated
