Twenty-seven Puerto Rican patients and 22 non-Puerto Ricans were
diagnosed by two symptoms characteristically seen in this syndrome:
albinism and defective blood platelets. Twenty-five of the 27 Puerto
Rican patients had a specific mutation (a small region of DNA
duplication) in the recently cloned gene, HPS, associated with the
syndrome.. Non-Puerto Ricans did not have this particular mutation.
Several different mutations are thought to lead to HPS. Patients with
and without the duplication were then compared using clinical and
The cause of this inherited disease, which was first described in 1959
and is named after its discoverers as the Hermansky-Pudlak
syndrome (HPS), is being investigated by physicians, geneticists, and
biochemists at the National Institute of Child Health and Human
Development (NICHD), the National Heart, Lung and Blood Institute
(NHLBI), and the National Eye Institute (NEI).
All HPS patients suffer from varying degrees of albinism (lack of skin
and eye pigment); this lack of pigment impairs the vision of patients
with albinism and often leads to involuntary rhythmic eye movements
called nystagmus. However, the most serious health problems are the
progressive deterioration in lung function, which is particularly
prevalent in the Puerto Rican patients carrying the DNA duplication,
and the tendency to bruise easily and bleed. At times women with
HPS need medical intervention during their menstrual cycles or at
childbirth. HPS patients are advised to avoid blood anticoagulants,
such as aspirin, and drugs can be used to prevent excessive bleeding
during dental extractions and other surgical procedures. The reason
HPS patients bleed easily is that their blood platelets are deficient in
so-called dense bodies. These subcellular organelles release their
contents to make other platelets stick together and form a clot.
Without the dense bodies, the clot forms very slowly.
The lung dysfunction begins with restrictive disease and then
progresses inexorably to death, usually in the fourth or fifth decade.
HPS patients have a biochemical storage disorder, that is, they
accumulate a fatty product called ceroid lipofuscin. The researchers
think that this causes inflammation in tissues such as bowel and lung.
Prolonged inflammation leads to fibrosis, which in the case of the lung
impairs its ability both to expel air and to exchange carbon dioxide for
From the gene sequence, researchers know what the protein encoded
by the HPS gene should look like, but it is not yet known what such a
protein actually does. According to Dr. William Gahl, the lead author
of the paper, many patients with albinism are not aware that they have
HPS. They are thus at risk for hemorrhage. Anyone suffering from
albinism who bruises easily should be checked for HPS, which is
diagnosed by observing blood platelets under the electron microscope
or by performing platelet aggregation studies.
Gahl's group in the NICHD has started a trial of an investigational
drug, which, in animal tests, has been shown to prevent inflammation.
With this drug, the researchers hope they can prevent the inflammation
that leads to the loss of lung function that shortens the lives of these