What is the most likely cause of a 7-year-old boy's clumsiness, difficulty concentrating, muscle weakness (2/5 in lower extremities), increased muscle tone, ataxic gait, and elevated very-long-chain fatty acids, with brain MRI showing signal abnormalities in parietooccipital deep white matter, while being treated with amphetamine-dextroamphetamine (amphetamine and dextroamphetamine) for attention-deficit/hyperactivity disorder (ADHD)?

Differential Diagnosis

• Single most likely diagnosis
  • Peroxisome transport protein mutation: This is the most likely diagnosis due to the presence of very-long-chain fatty acids in laboratory studies, which is a hallmark of peroxisomal disorders, such as adrenoleukodystrophy. The MRI findings of signal abnormalities in parietooccipital deep white matter bilaterally also support this diagnosis.
• Other Likely diagnoses
  • Medication adverse effect: Although less likely, the patient's symptoms could be related to an adverse effect of amphetamine-dextroamphetamine, particularly given the recent initiation of this medication. However, the laboratory and MRI findings are not typical of a medication adverse effect.
  • Mitochondrial abnormality: Mitochondrial disorders can present with a wide range of symptoms, including clumsiness, difficulty concentrating, and increased muscle tone. However, the specific laboratory and MRI findings in this case are more suggestive of a peroxisomal disorder.
• Do Not Miss diagnoses
  • None of the options provided are classic "do not miss" diagnoses that would be deadly if missed, but it's essential to consider other potential causes of the patient's symptoms, such as:
    • Vitamin B12 deficiency: Although not listed as an option, vitamin B12 deficiency can cause similar neurological symptoms and should be considered in the differential diagnosis.
• Rare diagnoses
  • Lipofuscin accumulation: This is a rare condition characterized by the accumulation of lipofuscin in cells, which can cause a range of symptoms, including neurological dysfunction. However, it is not typically associated with the specific laboratory and MRI findings in this case.
  • Psychosocial abnormality: This is unlikely to be the primary cause of the patient's symptoms, given the objective findings on examination and laboratory studies. However, psychosocial factors may contribute to the patient's overall presentation and should be considered in the broader context of their care.