CASE: Disoriented and delusional
Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.
At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.
Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.
The authors’ observations
FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).2 FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.5 In patients with no family history of FD, accurate diagnosis may not be made until adulthood.
Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.1 However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.2
Table 1
Typical signs and symptoms of Fabry’s disease
| Typical time at onset | Signs/symptoms |
|---|---|
| Childhood and adolescence (age ≤16) | Neuropathic pain Ophthalmologic abnormalities (cornea verticillata and tortuous retinal blood vessels) Hearing impairment Dyshidrosis (hypohidrosis and hyperhidrosis) Hypersensitivity to heat and cold Gastrointestinal disturbances and abdominal pain Lethargy and tiredness Angiokeratomas Onset of renal and cardiac signs (eg, microalbuminuria, proteinuria, abnormal heart rate variability) |
| Early adulthood (age 17 to 30) | Extension of any of the above Proteinuria and progressive renal failure Cardiomyopathy Transient ischemic attacks, strokes Facial dysmorphism |
| Later adulthood (age >30) | Worsening of any of the above Heart disease (eg, left ventricular hypertrophy, angina, arrhythmia, and dyspnea) Transient ischemic attacks, strokes Osteopenia and osteoporosis |
| Source: Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. QJM. 2010;103(9):641-659, by permission of Oxford University Press | |
HISTORY: Cognitive deterioration
Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam6 at that time was 28 out of 30, which was within normal limits.
After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.
Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).
The authors’ observations