A 15-year-old, previously healthy boy is brought to the clinic by his mother due to declining academic performance and change in behavior. The mother says that the patient used to be a straight A student but has been struggling to keep up in class for the last 3 months. He has also been uncharacteristically moody and irritable. She says, "I recently saw him talking to a wall, but when I asked him about it, he told me to mind my own business." When interviewed privately, the patient says he has been hearing voices at times but is unable to understand what they are saying. Vital signs are within normal limits. Growth tracks above the 60th percentile. Facial expressivity is diminished. The patient's voice is soft, and he has excess saliva. Motor examination shows increased tone in the arms and a mild tremor. Mental status examination is significant for an irritable affect and minimal eye contact. The most likely cause of this patient's underlying condition is an abnormality in which of the following physiologic processes?

Question

A 15-year-old, previously healthy boy is brought to the clinic by his mother due to declining academic performance and change in behavior.  The mother says that the patient used to be a straight A student but has been struggling to keep up in class for the last 3 months.  He has also been uncharacteristically moody and irritable.  She says, "I recently saw him talking to a wall, but when I asked him about it, he told me to mind my own business."  When interviewed privately, the patient says he has been hearing voices at times but is unable to understand what they are saying.  Vital signs are within normal limits.  Growth tracks above the 60th percentile.  Facial expressivity is diminished.  The patient's voice is soft, and he has excess saliva.  Motor examination shows increased tone in the arms and a mild tremor.  Mental status examination is significant for an irritable affect and minimal eye contact.  The most likely cause of this patient's underlying condition is an abnormality in which of the following physiologic processes?

Quizplus · Accepted Answer

11ec25c8_d789_ec47_bc81_71edcf14f9b1_MD0003_00 This adolescent has new-onset psychosis, as evidenced by impaired reality through auditory hallucinations. With an abnormal neurologic examination (eg, tremor, hypertonia, facial stiffness), these findings are concerning for parkinsonism due to Wilson disease. Wilson disease is an autosomal recessive disorder characterized by defective hepatic copper transport, resulting in copper accumulation throughout the body. Initial copper buildup occurs within the liver, leading to hepatocellular apoptosis and release of free copper into the bloodstream. Extrahepatic copper is then deposited in various tissues, including the CNS, kidney, and cornea. The basal ganglia is the primary site of deposition in the CNS and accounts for the movement abnormalities seen in Wilson disease. Because the basal ganglia, frontal cortex, and limbic system communicate, copper buildup also affects mood and cognition. defective hepatic copper transport Neuropsychiatric symptoms often precede hepatic symptoms, such as hepatomegaly or jaundice, in teenagers and may be mistakenly attributed to normal adolescence or primary psychiatric illness. Symptoms may be subtle (eg, personality change, academic decline, irritability) or more severe, as in this patient. Neurologic findings can also include dysarthria, dystonia, and tremor. This patient's diminished expressivity, soft voice, and pooled saliva are consistent with parkinsonism seen in Wilson disease. (Choice A) Very-long-chain fatty acid accumulation occurs in X-linked adrenoleukodystrophy, which can present with academic difficulties and behavioral abnormalities in early childhood or adolescence. Weakness, ataxia, and paralysis can occur, but tremor and parkinsonism would not be seen. (Choice C) Hereditary hemochromatosis is an autosomal recessive disorder characterized by increased absorption of iron. Symptoms include fatigue and hepatic dysfunction, but neuropsychiatric symptoms would not be seen. (Choice D) Fanconi syndrome, characterized by proximal tubular dysfunction, occurs in Wilson disease due to renal copper deposition. This complication is a result and not the cause of impaired cellular copper transport. (Choice E) Thyrotoxicosis due to hyperthyroidism can cause tremor and altered mental status (eg, agitation, delirium) or frank psychosis. However, these patients typically have tachycardia, high fever, and goiter, none of which are present in this case. Educational objective: New-onset psychosis in an adolescent with neurologic dysfunction (eg, tremor, parkinsonism) raises concern for Wilson disease. Pathogenesis involves defective hepatocellular copper transport, leading to copper accumulation in the liver and basal ganglia. References: Psychiatric aspects of Wilson disease: a review. (http://www.ncbi.nlm.nih.gov/pubmed/24120023) Misidentification of Wilson disease as schizophrenia (1998-2013): case report and review. (http://www.ncbi.nlm.nih.gov/pubmed/29200569) Wilson disease. (http://www.ncbi.nlm.nih.gov/pubmed/28723019)

A 15-Year-Old, Previously Healthy Boy Is Brought to the Clinic