Gaucher disease with pathological femoral fracture:
A case report with review of literature
University of Geneva, Switzerland
Submission: June 03, 2019; Published: June 25, 2019
*Corresponding author: Daniel Stoecklin, Associate Professor, Centre for Children’s Rights Studies, University of Geneva, Switzerland
How to cite this article: Daniel Stoecklin. Gaucher disease with pathological femoral fracture:
A case report with review of literature. Acad J Ped Neonatol. 2019; 7(5): 555780. DOI: 10.19080/AJPN.2019.07.555780
Gaucher disease is a rare multisystemic disease caused by a genetic deficiency of lysosomal glucocerebrosidase. Bone involvement in type 1 Gaucher disease is common. It ranges from simple asymptomatic osteopenia to more serious expressions type of osteonecrosis and fractures. Its support remains problematic in our country due to the lack of the specific means of diagnosis and monitoring parameters. We report the observation of a patient who develops a displaced fracture of the femur during Gaucher disease type 1 who did not undergo surgery because of haematological problems, including thrombocytopaenia. Through this case, we want to stress the importance of enzymotherapy in Gaucher disease to prevent certain irreversible damages, avoid certain complications and especially improve the quality of life of our patients, hence the need to facilitate access to this therapy in Morocco.
Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder secondary to a deficiency in glucocerebrosidase. Depending on the degree of the deficit, the clinical picture will be multisystemic with varying degrees of severity and evolution leading to significant psychological suffering. [1,2].
The Gaucher disease has benefited from spectacular advances both in diagnostic and treatment through the development of specific therapies allowing a normal life expectancy. However, the quality of life of these patients is very altered because of organomegaly, sometimes severe thrombocytopenia, but also bone degradation leading to a major functional disability with certain irreversible lesions justifying the interest of an early diagnosis.
We try, through this observation, to draw attention to the impact of this disease on the quality of life, especially without the enzymatic treatment, while trying to study the pathophysiology of Gaucher osteopathy, the clinical and radiological features and treatment options and insist on the recommendations during the follow-up through a review of the literature.
A 16-year-old girl, from a consanguineous marriage, followed for type 1 Gaucher disease since the age of 9: the diagnosis was suspected in front of an abdominal distention with hepatosplenomegaly associated with pancytopenia. The disease was confirmed by a medullary and hepatic histological study. She was treated symptomatically by blood transfusions (> 3 / year) and never had specific treatment by enzymotherapy for lack of financial means and social security.
Throughout her follow-up, the patient presented two fractures (one of the Radius and the other of the humerus) following minimal traumatisms associated with an osteopenia discovered by osteodensitometry.
In the course of her last stay at the hospital for blood transfusion, the patient fell from her height with an impact point at the left thigh, causing her a total functional impotence of the lower limb with pain and swelling.
X-Rays of the left femur showed a displaced diaphyseal fracture on a pathological bone with cortical thinning, bone demineralization and multiple lytic images (Figure 1A & 1B).
Given the minimal displacement of the femur fracture on a
pathological bone and the high risk of intraoperative bleeding,
the patient received orthopedic treatment by plaster cast
immobilization for 10 weeks in adjunction to a medical treatment
based on analgesics, with a good evolution (Figure 2).
Gaucher disease, is an inherited lysosomal storage disorder
, is a multisystemic condition that results from autosomal
recessive mutations in the gene encoding glucocerebrosidase. GD
is the most prevalent lysosomal disorder  with a prevalence for
type 1 of about 1/40 000 in the general population, and with a
higher frequency in the Ashkenazi Jewish population .
The history of bone symptomatology varies from one patient
to another due to the chronicity and unpredictable progression
of Gaucher’s disease, ranging from asymptomatic individuals to
those with a damaged skeleton. The age of onset of symptoms is on
average 20 years with extremes ranging from 2 to 80 years [6,7].
Bone disease in Gaucher patients is one of the most disabling
features of the disease, so the possibility of knowing the
mechanisms underlying the bone pathology is a main challenge to
ameliorate the quality of life of patients.
Gaucher osteopathy is mainly due to the progressive
accumulation of overload cells in the bone marrow, which has two
main consequences: a spinal volume expansion and an abnormal synthesis of pro-inflammatory cytokines by these macrophages
that promote bone resorption. In addition, interactions between
Gaucher cells, osteoclasts, osteoblasts and mesenchymal cells
impair bone homeostasis in Gaucher disease [8,9].
Skeletal involvement is very common in Gaucher’s disease: 70
to 100% of cases in types 1 and 3 . It is not always correlated
with the systemic severity of the disease but is the leading cause
of morbidity and disability.
Almost all GD patients develop skeletal complications,
consisting mainly of remodeling failure, osteopenia, osteoporosis,
marrow infiltration, avascular necrosis, and osteolysis .
Patients could be asymptomatic with or without radiological
signs or present symptoms including bone pain involving one limb
or joint, avascular necrosis, or pathological fractures.
An international registry of Gaucher patients worldwide
revealed that 62% of them had some form of radiologic bone
disease and 43% experienced bone pain [4,11]
Epidemiological data on fractures are few and their link with
the decrease in BMD in this context is poorly understood. In the
global registry, a fracture was reported in 108 patients out of 706
(15%) and “osteopenia” in 300 patients out of 706 (42%) .
Bone radiographic abnormalities are found in more than 95%
of patients, essential abnormalities to know both for the detection
of the disease and for its follow-up .
According to the recommendations, any patient suffering
from type 1 Gaucher disease should benefit from an initial
appraisal, ideally comprising whole femoral MRIs in coronal
section, standard radiographs (including a profile spine, femurs
in anteroposterior view including the heads femoral and knee
and other symptomatic site) and measurement of bone density by
dual-energy X-ray absorptiometry .
The bone involvement should be monitored regularly by
renewing these exams every 1 to 2 years or more in case of active
In case of bone involvement, the therapeutic objectives are
precise in children :
a. reduce or eliminate bone pain within 1 to 2 years;
b. prevent painful bone crises;
c. prevent osteonecrosis and subchondral joint collapse;
d. increase cortical and trabecular bone mineral density at
In addition to symptomatic treatments (analgesics, even
nonsteroidal anti-inflammatory drugs, bisphosphonates,
orthopedic management of fractures or osteonecrosis), enzyme
replacement therapy is the standard treatment for type 1 Gaucher
Treatment with imiglucerase CEREZYME® at a dose of 60U/
kg every 14 days allowed, in 33 treatment-naive patients over a
period of 2 years, to reduce the frequency and intensity of bone
pain and to improve bone density at the lumbar and femoral level,
without it being possible to affirm a preventive effect on fracture
Unfortunately, although it is effective, enzyme replacement
therapy can not reverse pre-existing destructive skeletal changes
once they are developed. This is why it is crucial to establish the
diagnosis and start the appropriate treatment as early as possible,
in order to avoid irreversible damage.
According to a recent study, we observed 5 prognostic factors
that predicted a higher probability of being free of bone disease:
optimal ERT compliance; early diagnosis; timely initiation of
therapy; ERT initiation dose ≥ 45 UI/kg/EOW; and the absence of
history of splenectomy .
To conclude, Gaucher disease is a genetic disease that is
probably under diagnosed. Bone involvement is probably the
most disabling aspect of this disease as we have seen in our
case. It represents the major complication in terms of morbidity.
Specific treatments are effective and improve bone density but
remain difficult to access in the Moroccan market and excessively