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Bipolar Disorder and Niemann-Pick Disease Type C

TO THE EDITOR: A number of neurodegenerative disorders that appear in adolescence or early adulthood are associated with the development of major mental illness. We present the case of a young man who was seen with a bipolar illness in the setting of the early-life diagnosis of 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.

Niemann-Pick disease type C is an autosomal-recessive disorder of cholesterol metabolism that has been reported to appear as a schizophrenia-like illness up to a decade before the onset of its characteristic cognitive decline, ataxia, and vertical supranuclear ophthalmoplegia (1, 2). It is caused by a mutation to either of the NPC1 or NPC2 genes, which are involved in intracellular cycling of sterols (3), causing an accumulation of cholesterol in neurons and resulting in axonal and neuronal loss in callosal, cerebellar, and hippocampal regions (4). To our knowledge, this is the first report of a bipolar-type illness in Niemann-Pick disease type C adding to the established literature suggesting that up to 40% of patients with adult-onset illness are seen with psychosis.

References

1. Josephs KA, Van Gerpen MW, Van Gerpen JA: Adult-onset Niemann-Pick disease type C presenting with psychosis. J Neurol Neurosurg Psychiatry 2003; 74:528–529[Abstract/Free Full Text]
2. Lossos A, Schlesigner I, Okon E, Abramsky O, Bargal R, Vanier MT, Zeigler M: Adult-onset Niemann-Pick type C disease: clinical, biochemical, and genetic study. Arch Neurol 1997; 54:1536–1541[Abstract/Free Full Text]
3. Ikonen E, Holtta-Vuori M: Cellular pathology of Niemann-Pick type C disease. Semin Cell Dev Biol 2004; 15:445–454[CrossRef][Medline]
4. Elleder M, Jirasek A, Smid F, Ledvinova J, Besley G: Niemann-Pick disease type C: study on the nature of the cerebral storage process. Acta Neuropathol 1985; 66:325–366[CrossRef][Medline]

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