“The disease of the Lady Madeline had long baffled the skill of her physicians.” —Edgar Allan Poe, “The Fall of the House of Usher.”

Dr. KSS’s paternal clan harbors a secret, a mysterious illness. Indeed, for many years, the diagnosis defied multiple specialists in and out of academic medical centers. Extensive diagnostic work-up was always non-contributory.

Dr. KSS’s paternal grandfather and grandmother had 5 children, all males. The oldest male died in infancy of unknown causes. The remaining 4 males are alive and range in ages from 86 to 79. Below these are referred to as brothers 1 through 4.

All was well until brother 2 noted insidious onset in his early 40’s of a gait disturbance with leg weakness. This problem gradually progressed until, by the age of 70 he was wheelchair-bound. Except for easily-controlled hypertension, he has no other illnesses. He is known to be without cardiovascular disease. He was a career Air Force officer who served in Vietnam, Germany, Morocco and Canada.

A similar process began in brother 1 during his early fifties, though beyond this his health has been good except for well-controlled hypertension. He was also an Air Force officer and nuclear missile avionics expert, and has been stationed in various places around the world. He is 86 and has been wheelchair-bound for over a decade.

Brother 3 is KSS’ father. He remains without evidence of neurological disease. He never served in the military. He was a career cinematographer.

Brother 4 began during his early 60’s having similar leg weakness difficulties, but his course of deterioration was more rapid and more severe. He is both the youngest and weakest of all the brothers. He was in the Army and stationed in Germany following WWII. He is a retired minister.

Some facts that may or may not be pertinent:
• (1) brother 2 in whom symptoms began earliest smoked cigarettes heavily. None of the other brothers smoked.
• (2) KSS’s grandfather died at age 55 of his first MI. He was portly, thought to be healthy except for hypertension, and a remarkably successful entrepreneur. He was also a carbohydrate junkie, typically consuming 16 bottles of Coca-Cola daily.
• (3) brother 4 had vocal cord cancer but is now disease-free as regards this
• (4) the mother of the brothers died in her late 70’s of widely-metastatic colorectal cancer. She had no evidence of neurological or muscular disease during her llfetime.
• (5) No siblings of the parents were known to have similar diseases though data is scant.
• (6) all the brothers are teetotallers
• (7) all 4 brothers sired children of both genders. All are alive, well and healthy.

Questions:
• (1) what is the underlying diagnosis?
  • (a) a late-onset polyneuropathy consequent to one of many vaccines three of the brothers were forced to receive as part of their military service
  • (b) a mitochondrial cytopathy
  • (c) a variant of an X-linked muscular dystrophy
  • (d) autoimmune polyneuropathy
• (2) Although the illness was never diagnosed by any of the physicians of the brothers, Dr. KSS made the correct diagnosis in 2013. He confirmed that diagnosis with a single test. What was the test?
  • (a) urine heavy metal screen
  • (b) mitochondrial DNA sequencing
  • (c) serum protein electrophoresis
  • (d) RFLP analysis for muscular dystrophy
  • (e) muscle biopsy
• (3) True or false: Smoking contributed to early onset of brother 2’s symptoms. If true, why?
• (4) Which one of the following commonly-used drugs could prove fatal to the afflicted brothers were they to receive a dose?
  • (a) aspirin
  • (b) gentamicin, an antibiotic
  • (c) Halothane anesthesia
  • (d) statins
• (5) Any of the daughters of the brothers could pass the illness to their children. True or false.
• (6) Dr KSS’s father remains disease-free at 81. Given his age, it is a near-certainty he will never be afflicted based on what is known about this class of disease
• (7) Of the biotech companies we like at this website, which one of the following is developing an agent that could conceivably help the afflicted brothers?
  • (a) $AUPH
  • (b) $CAPR
  • (c) $RETA
  • (d) $CWBR
  • (e) $MGEN