Bipolar Disorder and Niemann-Pick Disease Type C

Mr. A was a 25-year-old man who was hospitalized for behavioral disturbances, including disturbed sleep and appetite, sexualized behavior, and disorientation. Born prematurely, he was diagnosed with jaundice and hepatosplenomegaly. Fibroblast testing confirmed deficient cholesterol esterification and positive filipin staining, and later mutation analysis revealed homozygosity for the I1061T mutation of the NPC1 (Niemann-Pick disease type C) gene. He attended a special educational program and was able to work and participate in musical theater. At age 18, he exhibited early cognitive decline, and at 23, his behavior became disturbed, with periods of increased wakefulness, elation, poor judgment, and disinhibition that lasted 2–3 weeks, every 1–2 months, with interepisode euthymia.

At a mental status examination, Mr. A was highly elevated, euphoric, and markedly sexually disinhibited, with sexualized thought content. There were no delusions, formal thought disorder, perceptual abnormalities, or ideas of harm. He was disoriented and distractible, and his judgment was poor. He showed dystonic hand posturing, although his power, reflexes, and sensations were normal. His speech was dysarthric, and he had limited upward and no downward saccades, although his lateral eye movements were preserved. He showed mild hepatosplenomegaly.

Magnetic resonance imaging of Mr. A’s brain showed mild generalized atrophy, prominent in cerebellar hemispheres and anterior temporal areas. His visual evoked potentials were normal. His full-scale IQ on WAIS-III-R testing was 64. He was diagnosed with bipolar I disorder, with rapid-cycling features. Initiation of sodium valproate, 500 mg b.i.d., resulted in significant stabilization of his elevated mood, leading to discharge. His improvement was sustained over 18 months of follow-up.