In 1949, a family member requested investigation of recent deaths of four of my 30- to 40-year-old male relatives (see Cousin F's Letter). Gerald T. Perkoff MD and Frank H. Tyler MD (at University of Utah in Salt Lake City) then initiated the "Utah" study of Alport syndrome. From findings of hematuria (red blood cells in the urine), Drs Perkoff and Tyler ascertained Alport syndrome in about 65 relatives, including myself. As males clearly suffered hearing loss and chronic renal failure, and died in uremia, I have thus since age 7 been interested in Alport syndrome, and in kidney disease in general.
I studied chemistry at Brigham Young University (BYU), then in 1964 finished a BS degree in chemistry at the California Institute of Technology (Caltech). In 1970 I completed a PhD in biochemistry from the University of California at Berkeley. During 1970-1973 I was a postdoctoral fellow of The Helen Hay Whitney Foundation at Karolinska Institutet in Stockholm. Then I came to the University of Utah School of Medicine, where from 1973-1994 I was active in the research faculty of the Departments of Biochemistry and of Internal Medicine. My curriculum vitae reflects my principal engagement in studies of copper and iron metabolism and of structure-function of proteins, as well as lesser time spent on research on Alport syndrome.
In Stockholm I met and married Elisabet Thor MD. She is now a practicing internist-nephrologist in Salt Lake City. We have two adopted children.
I revived Dr Perkoff's and Dr Tyler's Alport study in 1973, and in 1978 helped found the Hereditary Nephritis Foundation (HNF). The Alport Study had only modest support from the March of Dimes, The HNF, and from the US General Clinical Research Centers (GCRC). I and nephrologist colleagues H. Allan Bloomer MD, William M. O'Neill Jr MD, Douglas P. Duffy MD, Martin C. Gregory MD, and others struggled for years clearing up the clinical description, and discerning that Alport syndrome was a family of diseases rather than one disease. Various biochemical approaches made little progress, and several wild goose chases persuaded me that it is indeed a bad idea to work on your own disease. A person who is his own doctor or lawyer has a fool for a client! Collaboration with geneticists eventually paid off, however. Sandra Hasstedt PhD and others in Dr Mark H. Skolnick's Division of Genetic Epidemiology (also at University of Utah) provided much illumination on X-linked inheritance and genetic heterogeneity of Alport syndrome.
I first received major support for the Alport Study in 1988, in the form of a (US) National Institute of Health (NIH) research grant. David F. Barker PhD and Pamela Fain PhD began serious molecular genetic studies, and Dr Gregory intensified family studies. Shortly thereafter, Dr Karl Tryggvason and colleagues at University of Oulu, Finland, found an X-linked gene for a subunit of basement membrane collagen. This result meshed nicely with old theories on causes of Alport syndrome, and with our previous mapping of the Alport gene in several large Utah Alport kindreds to chromosomal region Xq22. Using Dr Tryggvason's DNA probes on DNA specimens from Utah families, Dr Barker then quickly found the first three causative mutations of Alport syndrome (Science 248:1224-1227, June 1990), thereby identifying the first known gene for an hereditary kidney disease and for an hereditary deafness. This story and subsequent developments will be found in greater detail in the Alport Syndrome Home Page and many associated webpages that I wrote and maintain if effort to stimulate research and education on Alport syndrome.
I had end-stage renal disease (ESRD) in 1981, and started hemodialysis. Two years later I received a kidney transplant from my Father, but after series of profound infections over three years, had to quit immunosuppressives and thus lost the kidney. I enjoyed chronic ambulatory peritoneal dialysis for about 30 months, but got peritonitis and had to go back on hemo. With this sequence of events (having ESRD and starting as a Medicare beneficiary, and Medicare automatically ending a year after transplantation, and then resuming dialysis and Medicare) I am one of the few who can truthfully say: My Medicare not only expired before I did, but also was resurrected! Recurrence of coccidioidomycosis (Valley fever) has forced my staying off the transplant list until better antifungals recently arrived. I developed extensive soft tissue calcification (tumoral calcinosis), lost a mineralized heart valve , and because of crippling muscular and joint disabilities had to retire 1/1/94. I am grateful for decades of university life and unfettered research. What I flatter myself to call my career, more than on research grants and pitiful faculty salaries, has depended upon robust emotional and financial support from my parents and wife.
With NIH and HNF support, Dr Barker, Dr Gregory, and Joyce C. Denison PhD continue the Alport Studies and Clinics, for which I now serve as occasional consultant. The Study now encompasses more than 250 Alport families, and Dr Barker has found the causative mutations in more than half of them. Dr Gregory organized the Fourth International Workshop on Alport Syndrome, April 15-17, 1999, in Salt Lake City, for the first time to include an educational Patient and Family Day. By now about 30 of my relatives have suffered end-stage renal disease (ESRD) and mostly died, although some are long-term survivors on dialysis or transplants. More than 200 of my relatatives are known to be gene carriers.
Elisabet (as physician) and I (as one of several patients) very much enjoyed dialy$i$ crui$e$, from Alaska to Vancouver in 7/97, and to eastern Caribbean islands in 3/99.
In autumn 1999 I received a successful cadaveric kidney transplant, and am feeling better and stronger each day. I hope to return to work.