Cases That Test Your Skills

The angry disciple

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Mr. J began to exhibit these psychotic symptoms in his early 50s; because the average age of onset of schizophrenia for males is approximately age 20 to 25, the likelihood of his presentation being the result of a primary psychotic disorder was low.1 Although less common, it was possible that Mr. J had developed late-onset schizophrenia, where the first episode typically occurs after approximately age 40 to 45. Mr. J also described that he was in a “great” mood but had grandiose delusions and had made recent impulsive decisions, which suggests there was a possible mood component to his presentation and a potential diagnosis of schizoaffective disorder or bipolar disorder with psychotic symptoms. However, before any of these diagnoses could be made, a medical or neurologic condition that could cause his symptoms needed to be investigated and ruled out. Further collateral information regarding Mr. J’s history and timeline of symptoms was required.

EVALUATION Family history reveals clues

All laboratory studies completed during Mr. J’s hospitalization are unremarkable, including complete blood count, basic metabolic panel, hepatic function panel, gamma-glutamyl transferase test, magnesium, phosphate, thyroid-stimulating hormone, vitamin B12, thiamine, folate, urinalysis, and urine drug screen. Mr. J does not undergo any head imaging.

Mr. J has not been in touch with his family since leaving his home approximately 3 months before he presented to the ED, and he gives consent for the inpatient team to attempt to contact them. One week into hospitalization, Mr. J’s sibling informs the team of a family history of genetically confirmed Huntington’s disease (HD), with psychiatric symptoms preceding the onset of motor symptoms in multiple first-degree relatives. His family says that before Mr. J first developed delusions 4 years ago, he had not exhibited any psychotic symptoms during periods of alcohol use or sobriety.

Mr. J does not demonstrate any overt movement symptoms on the unit and denies noting any rigidity, change in gait, or abnormal/uncontrolled movements. The inpatient psychiatric team consults neurology and a full neurologic evaluation is performed. The results are unremarkable outside of his psychiatric symptoms; specifically, Mr. J does not demonstrate even subtle motor signs or cognitive impairment. Given Mr. J’s family history, unremarkable lab findings, and age at presentation, the neurology team and inpatient psychiatry team suspect that his psychosis is likely an early presentation of HD.

The authors’ observations

Genetics of Huntington’s disease

Huntington’s disease is an autosomal dominant neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats within the Huntingtin (HTT) gene on chromosome 4, which codes for the huntingtin protein.2,3 While the function of “normal” huntingtin protein is not fully understood, it is known that CAG repeat expansion in the HTT gene of >35 repeats codes for a mutant huntingtin protein.2,3 The mutant huntingtin protein causes progressive neuronal loss in the basal ganglia and striatum, resulting in the clinical Huntington’s phenotype.3 Notably, the patient’s age at disease onset is inversely correlated with the number of repeats. For example, expansions of approximately 40 to 50 CAG repeats often result in adult-onset HD, while expansions of >60 repeats are typically associated with juvenile-onset HD (before age 20). CAG repeat lengths of approximately 36 to 39 demonstrate reduced penetrance, with some individuals developing symptomatic HD while others do not.2 Instability of the CAG repeat expansion can result in genetic “anticipation,” wherein repeat length increases between generations, causing earlier age of onset in affected offspring. Genetic anticipation in HD occurs more frequently in paternal transmission—approximately 80% to 90% of juvenile HD cases are inherited paternally, at times with the number of CAG repeats exceeding 200.3

Continue to: Psychiatric manifestations of Huntington's disease

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