Wednesday, August 1, 2018

Alport Syndrome

I recently saw a patient in clinic with long-standing hematuria with numerous family members on her mother’s side with hematuria.  She now presented with proteinuria but stable renal function.  Collagen IVa disease was highly suspected and genetic sequencing identified a heterozygous carrier for a previously characterized pathogenic mutation in Col4a5.

In the process of taking care of this patient who was heterozygous for X-linked Alport’s syndrome, I wondered, “Who is Dr. Alport?”.
Dr. Arthur Cecil Alport was a physician originally from South Africa who attained his medical training in Edinburgh, Scotland. He had many different interests initially studying malaria abroad and then practicing medicine in London before becoming a Professor in Egypt where he fought for the care of poor patients.  He showed that with careful observation one can provide valuable insights into a specific disease. 
Dr. Alport was not the first to identify the entity of hereditary hemorrhagic nephritis.  Initially, William Howship Dickinson described a family with 11 out of 16 members with albuminuria in 1875.  Subsequent studies by Guthrie and Hurst identified families with hematuria and kidney disease of varying severity.  Dr. Alport saw a patient from the Guthrie/Hurst cohort which he further studied and published with the title, “Hereditary Familial Congenital Haemorrhagic Nephritis”, in the British Medical Journal in 1927 which led to the identification of the disease as Alport’s syndrome. 
In this paper, he found a number of female members of the family had hematuria but did not develop edema, heart failure, and kidney failure, a fate reserved for a selected few male members of the family.  He also noted numerous female members with profound deafness that at time was not associated with hematuria.  Though he acknowledged the hereditary nature of this disease, he also found hematuria and albuminuria were exacerbated by streptococcal infection which he had limited success in recreating in rabbits. 
The history of medicine often provides an interesting context for our current understanding of human disease.  By observing the association of deafness in families with hereditary hematuria, Dr. Alport brought to light a key identifier of the disease entity.  This identification ultimately led to the disease to be associated with his name though the renal phenotype of familial hematuria was discovered by prior investigators.
Posted by Ankit Patel, Nephrology Fellow, Joint BWH/MGH Fellowship Program

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