A 41-year-old man with trisomy 21 is evaluated in the clinic due to cognitive decline. The patient has a history of moderate intellectual disability, but his higher cognitive functions have become progressively impaired in the past several years. He previously volunteered at a community library but recently lost his position as he could no longer perform his duties. The patient is now completely dependent on a caregiver for assistance with his activities of daily living such as getting dressed, bathing, and using the toilet. The patient keeps wandering in the group home and has become lost on several occasions. Which of the following is most likely to be increased in this patient?

Question

A 41-year-old man with trisomy 21 is evaluated in the clinic due to cognitive decline.  The patient has a history of moderate intellectual disability, but his higher cognitive functions have become progressively impaired in the past several years.  He previously volunteered at a community library but recently lost his position as he could no longer perform his duties.  The patient is now completely dependent on a caregiver for assistance with his activities of daily living such as getting dressed, bathing, and using the toilet.  The patient keeps wandering in the group home and has become lost on several occasions.  Which of the following is most likely to be increased in this patient?

Quizplus · Accepted Answer

11ec160b_3782_4bcf_9249_d95f06b65017_MD0001_00 Trisomy 21, also known as Down syndrome, is the most commonly diagnosed chromosomal anomaly in liveborn neonates. Typical symptoms include intellectual disability, congenital abnormalities (eg, gastrointestinal, cardiac), physical growth delay, and characteristic facial features (eg, flat facies, protruding tongue, epicanthic folds, oblique palpebral fissures). Many patients with trisomy 21 develop early-onset Alzheimer disease (AD), defined as diagnosis of AD age ≤65, with some developing AD as early as the fourth decade of life. Characteristic pathologic changes associated with AD involve accumulation of intracellular neurofibrillary tangles and extracellular amyloid-beta plaques: The amyloid precursor protein (APP) gene is located on chromosome 21. The extra copy of APP present in trisomy 21 is thought to accelerate amyloid accumulation and lead to early-onset AD. (Choice A) Amyloid A protein is an acute-phase reactant that is associated with the development of multisystemic amyloidosis (AA amyloidosis) in reaction to chronic disease states (eg, rheumatoid arthritis, inflammatory bowel disease). (Choice C) Apolipoprotein E is found in 3 allelic variations: epsilon 2, 3, and 4. Those with 1 or 2 copies of the epsilon 4 allele are at greater risk for late-onset AD (ie, AD diagnosed at age >65) compared with those without the allele. (Choice D) Expansion of CAG trinucleotide repeats in the HTT gene, which codes for huntingtin protein, is responsible for Huntington disease. Individuals with this condition typically have movement abnormalities (eg, chorea), psychiatric symptoms, and dementia. (Choice E) Islet amyloid polypeptide is a normal secretory product of pancreatic beta cells that forms cytotoxic deposits in type 2 diabetes mellitus, impairing beta-cell function. Educational objective: Patients with trisomy 21 (Down syndrome) have 3 copies of the amyloid precursor protein gene located on chromosome 21. This increases amyloid-beta accumulation in the brain, placing these patients at high risk for developing early-onset Alzheimer disease. __________ References: Aging in Down syndrome and the development of Alzheimer's disease neuropathology. (http://www.ncbi.nlm.nih.gov/pubmed/26651341)

A 41-Year-Old Man with Trisomy 21 Is Evaluated in the Clinic