Quality of Life Research, 7, pp. 521–534
©
1998 Kluwer Academic Publishers Quality of Life Research
.
Vol 7
.
1998
521
The impact of Gaucher disease and its treatment
on quality of life
R. P. Hayes,* K. A. Grinzaid, E.B. Duffey and L. J. Elsas II
Emory University Center for Clinical Evaluation Sciences, Decatur, GA, USA
(R. P. Hayes); Kerr L. White Institute for Health Services Research, Decatur, GA, USA
(R. P. Hayes, E. B. Duffey); Division of Medical Genetics, Department of Pediatrics,
Emory University School of Medicine, Atlanta, GA, USA (K. A. Grinzaid, L.J. Elsas II)
To obtain information about how Gaucher disease
and its treatment, specifically enzyme replacement
therapy, affect patients’ health-related quality of life
(HRQoL), we interviewed 16 patients with type I
Gaucher disease (range 8–67 years). All but three
patients had been receiving enzyme replacement
therapy for at least 6 months. The quality of life
factors examined for these patients included physical
health, social life, emotional health, financial burden,
future plans and satisfaction with health care. The
results indicated that bone pain and chronic fatigue
interfered with school, job and social activities and
were the most debilitating symptoms of Gaucher
disease. Most patients experienced a significant
increase in energy level from therapy and reported
significant improvements in quality of life. Most
patients did not perceive an effect of Gaucher
disease on their overall emotional health, but some
patients expressed anxieties about the discomfort,
inconvenience and high costs of therapy. We
conclude that a measure of HRQoL for Gaucher
patients should include a generic core of items
supplemented by disease-specific items designed to
assess the changes in symptoms and in the occupa-
tional, recreational, social and emotional aspects of
patients’ lives that occur as a result of disease
progression and/or management.
Qual. Life Res. 7:521–534 © 1998 Kluwer Academic Publishers
Key words: Gaucher disease; health-related quality of life
(HRQoL); enzyme replacement therapy.
Introduction
Gaucher disease type I is a non-neuronopathic, debili-
tating disease resulting from inherited deficiency of
the lysosomal enzyme, glucocerebrosidase. The
substrate in this blocked reaction, glucocerebroside,
accumulates in macrophages of the reticuloen-
dothelial system (particularly the bone marrow, liver
and spleen) and produces a combination of haemato-
logic, hepatosplenic and skeletal symptoms along
with chronic fatigue. There is an extremely wide range
of disease expression, depending on both the degree
of enzyme impairment and other epigenetic
phenomena.
Gaucher disease is a panethnic disorder which is
very common (with a frequency as high as 1 in 500) in
the Ashkenazi Jewish population and relatively rare
(with a frequency of 1 in 60,000 or less) in other
groups. Over 50 mutations in the Gaucher gene have
been identified.
1
The most common mutation in type I
disease among Ashkenazi Jews is N370S, which is a
missense mutation in which serine is substituted for
an asparagine at amino acid 370. This mutation
produces a normal amount of enzyme but with
reduced activity. Other more severe mutations
produce no functional enzyme. Some patients who are
homozygous for N370S (i.e. N370S/N370S)
experience few if any symptoms and can only be
identified by demonstrating impaired glucere-
brosidase activity and the mutations. Other patients
with this genotype may have mild to moderate
disease symptoms with a mean age of onset of 30
years. Patients who are heterozygous for two different
mutations (e.g. N370S/L444P or N370S/IVS2(+1))
often suffer earlier and progressive debilitation. This
debilitation usually begins in childhood with
hepatosplenomegaly, bleeding diatheses associated
with thrombocytopenia and/or bone involvement.
2, 3
Historically, Gaucher disease was managed sympto-
matically by splenectomy, blood transfusion and
orthopaedic procedures.
4
Bone marrow transplantation
has been attempted but carries high morbidity and
mortality risks. The development of a highly effective
and safe enzyme replacement therapy (Ceredase
(alglucerase injection), which is manufactured by the
*To whom correspondence should be addressed at Emory
University Center for Clinical Evaluation Sciences, 101 W.
Ponce de Leon Avenue, Suite 620, Decatur, GA 30030, USA.
Tel: (404) 778-5976; Fax: (404) 778-5995.