Saturday, December 27, 2008

Is the incidence of sickle cell disease rising?

In 1949, Linus Pauling and coworkers showed that sickle cell anemia is a disease produced by an inherited alteration in hemoglobin, producing a molecule that is separable from normal hemoglobin, by electrophoris. Electrophoresis is still used to distinguish sickle hemoglobin from normal hemoglobin.

In 1956, Vernon Ingram and J.A. Hunt sequenced the hemoglobin protein molecule (normal and sickle cell) and showed that the inherited alteration in sickle cell hemoglobin is due to a single amino acid substitution in the protein sequence.

Because sickle cell hemoglobin can be detected by a simple blood test, it was assumed, back in the 1950s, that new cases of this disease would be prevented through testing, followed by genetic counseling. Today, there are a number of private and public organizations that work to reduce the incidence of sickle cell disease.

I have been interested in knowing whether sickle cell incidence is decreasing in the U.S. population. Despite Pubmed and web searches, I have not been able to find a single data source on the subject.

I decided to investigate using the CDC (U.S. Centers for Disease Control and Prevention) mortality data sets. In a separate document, I've provided methods for acquiring and analyzing the CDC public use mortality files.

For the current study, I downloaded the mortality files for the years 1996, 1999, 2002, and 2004, all of which contain de-identified records listing multiple conditions, coded in ICD-10 (International Classification of Disease, version 10), for the underlying causes of death and other significant conditions, found on U.S. death certificates.

I parsed through every record (about 5 Gigabytes of raw data), and compiled the following results.

In 1996, U.S. cases with sickle cell disease in death certificates is 708
In 1996, U.S. rate of sickle cell disease in death certificates is 30.54 per 100,000

In 1999, U.S. cases with sickle cell disease in death certificates is 799
In 1999, U.S. rate of sickle cell disease in death certificates is 33.36 per 100,000

In 2002, U.S. cases with sickle cell disease in death certificates is 827
In 2002, U.S. rate of sickle cell disease in death certificates is 33.79 per 100,000

In 2004, U.S. cases with sickle cell disease in death certificates is 876
In 2004, U.S. rate of sickle cell disease in death certificates is 36.47 per 100,000

For all four years examined, there has been a steady, increasing trend in the number of death certificates listing sickle cell disease as a cause of death or a significant condition at the time of death. Likewise, the overall rate (per 100,000 certificates) has steadily increased in every sampled year, covering 1996 to 2004.

Does this mean that efforts to reduce the incidence of sickle cell disease have failed? No. Death certificate data is unreliable. Whether a doctor thinks of adding sickle cell disease as a medical condition, on the death certificate, may depend on a variety of factors (as discussed previously). However, when you're dealing with very large numbers, trends usually reflect reality.

The best data would be natality incidence rates, by year, measured between about 1960 and the present. However, I have not been able to find that kind of data, and the CDC mortality files may be the next-best option.

For those interested in conducting an independent analysis of the same data, here are the locations of the files that I downloaded by anonymous ftp from the CDC server (


2002, 2004

1996 data file that combines icd9 and 1cd10 data

If anyone has access to more reliable data, or a different set of results, please add a comment to this blog.

- © 2008 Jules Berman

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In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

I urge you to read more about my book. There's a generous preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

tags: common disease, orphan disease, orphan drugs, rare disease, disease genetics, cdc, epidemiology, sickle cell disease, sickle cell anemia, sickle cell anaemia, cdc, death certificate data, U.S. mortality tables, understanding death certificates, incidence of sickle cell disease, rate of sickle cell disease, cause of death, icd10, international classification of diseases