clinical manifestation . diagnosis , treatment , prognosis

1. GAUCHER DISEASE
Dr.mazin M.kadhim
Nelson textbook of paediatrics
20TH EDITION

2. This disease is a multisystemic lipidosis
characterized by hematologic
abnormalities, organomegaly, and
skeletal involvement, the latter usually
manifesting as bone pain and pathologic
fractures . It is one of the most common
lysosomal storage diseases and the most
prevalent genetic defect among
Ashkenazi Jews.

3. There are 3 clinical subtypes delineated by
the absence or presence and progression of
neurologic manifestations:
type 1 or the adult, nonneuronopathic form;
type 2, the infantile or acute neuronopathic
form; and
type 3, the juvenile or subacute
neuronopathic form. All are autosomal
recessive traits.

4. Clinical manifestations
Gaucher Diz. type 1
•Thrombocytopenia & its manifestation
•Anemia & its manifestation
• Hepatomegaly with or without elevated
liver function test results
•Splenomegaly
•Bone pain.
•Pulmonary involvement
•Growth retardation

6. Erlenmeyer flask deformity of the distal femur

7. Gaucher disease type 2
is a rare form and does not have an ethnic
predilection. It is characterized by a rapid
neurodegenerative course with extensive
visceral involvement and death within the first
years of life.

8. It presents in infancy with
•increased tone
•strabismus
•organomegaly
•Failure to thrive
•stridor caused by laryngospasm
•psychomotor regression
•death typically occurs secondary to respiratory
compromise.

9. Gaucher disease type 3
presents with clinical manifestations that are
intermediate to those seen in types 1 and 2, with
presentation in childhood and death by age 10-15 yr. It
has a predilection for the Swedish Norrbottnian
population, among whom the incidence is
approximately 1 in 50,000.

10. Neurologic involvement is present.
Type 3 disease is further classified as types 3a
and 3b based on the extent of neurologic
involvement and whether there is progressive
myotonia and dementia (type 3a) or isolated
supranuclear gaze palsy (type 3b).

11. Gaucher disease should be considered in the
differential diagnosis of
patients with unexplained organomegaly,
who bruise easily,
have bone pain,
or have a combination of these conditions

12. The pathologic hallmark of Gaucher disease is the
Gaucher cell in the reticuloendothelial system,
particularly in the bone marrow. The presence of this
cell in bone marrow and tissue specimens is highly
suggestive of Gaucher disease, although it also may be
found in patients with granulocytic leukemia and
myeloma.

13. Prenatal diagnosis
is available by determination of enzyme
activity and/or the specific family mutations
in chorionic villi or cultured amniotic fluid
cells.

14. Treatment of patients with Gaucher disease
type 1
includes enzyme replacement therapy. The
efficacy of enzyme replacement therapy with
mannose-terminated recombinant human acid β-
glucosidase has definitively been demonstrated.

15. Most symptoms (organomegaly, hematologic
indices, bone pain) are reversed by enzyme
replacement therapy (60 IU/kg) administered
by intravenous infusion every other week
and the bone involvement can be stabilized
or improved.

16. A two additional enzyme preparations are
approved by the FDA for the treatment of type 1
Gaucher disease, including
velaglucerase alfa (VPRIV, Shire HGT), which is
produced in human fibrosarcoma cells, and
taliglucerase alfa (Uplyso, Protalix
Biotherapeutics), which is produced in carrot
cells.

17. Treatment of patients with Gaucher disease
type 2 & 3
Although enzyme replacement does not alter the
neurologic progression of patients with Gaucher
disease types 2 and 3, it has been used in selected
patients as a palliative measure, particularly in
type 3 patients with severe visceral involvement.

18. Alternative treatments, including the use of
oral substrate reduction agents designed to
decrease the synthesis of glucosylceramide
by chemical inhibition of glucosylceramide
synthase (e.g., miglustat), also are available.

19. A small number of patients have undergone bone
marrow transplantation (BMT), which is curative
but is associated with significant morbidity and
mortality from the procedure, limiting the
selection of appropriate candidates.