Patient
Care and Treatment
Cited literature
This
website deals with clinical management, diagnosis, therapeutic options of the
disease and genetic counselling in general terms. The information in this
website can by no means substitute for medical advice to the individual patient
or family.
Because
of the increased radiosensitivity of NBS patients, ionising radiation must be
avoided for therapeutic uses and, if not strictly necessary, also for diagnostic
uses.
Evaluation
of the immunological profile is required at the time of diagnosis. Afterwards,
the evolution of humoral (every 6 months) and cellular immunity (once a year)
needs to be followed up.
Infections
must be carefully monitored and adequately treated. Screening
for Epstein-Barr virus, cytomegalovirus, hepatitis B virus, and hepatitis C
virus is recommended once a year, or when infection is suspected.
Intravenous
immunoglobulin [IVIG] therapy is established according to the degree of immune
deficiency, and is indicated in patients with agammaglobulinemia and in all
children with low levels of IgG2. Before
IVIG is started, the presence of anti-IgA antibodies must be determined in
patients with IgA deficiency. In such cases, the subcutaneous administration of
immunoglobulins is advocated.
Antibiotic
prophylaxis is recommended in children with urinary infections due to congenital
malformations and can also be considered in patients with recurrent respiratory
infections.
Very recently, New et al. (2005) described the use of bone marrow
transplantation (BMT) for NBS.
Their patient with a presumed diagnosis of Fanconi anemia (FA) underwent BMT, at the age of
3 years, in order to correct his severe immunodeficiency. The conditioning
regimen was appropriate to his presumed diagnosis of FA (with
a reduced dose of an alkylating agent and irradiation), and was
well tolerated with no major
complications.
The patient was then demonstrated to be homozygous
for a 1089C>A
mutation in the NBS1 gene, and his diagnosis was changed into NBS.
At 3 years post
transplantation, the patient is stably engrafted with mixed chimerism:
80% donor mononuclear cells, although only 10% donor myeloid cells.
Although careful follow-up is required, his
immune deficiency does appear to have been successfully treated by the BMT, as the
child has normal cell mediated immunity (as assessed by T cell numbers and
mitogenic proliferation) and normal humoral immunity (as assessed by normal
responses to vaccination antigens).
As pointed out by the Authors, concern
remains about short and long-term toxicity as the result of the conditioning
regimen in NBS, including increased development of malignancies. However, it is
possible that BMT, using a modified conditioning protocol, may have a future
role in the treatment of NBS patients with severe immunodeficiency.
Systematic
and periodic screening for cancer development is required, particularly
for haematological malignancies, which account for the 85-90% of tumours in NBS
patients.
Treatment
of malignancies may be difficult. Conventional doses
of radiation used in radiotherapy and chemotherapy drugs may be lethal in
patients with NBS or lead to severe toxic complications and/or second malignancy.
However, achieving long term remission is possible and curative therapy for
cancer should be attempted. A modified treatment protocol must be adopted:
radiation therapy and radiomimetics have to be avoided, and so should alkylating
agents and epipodophyllotoxins;
the dose of
methotrexate should be limited
and the chemotherapy doses,
in general, should be reduced and an estimation of the individual tolerance and dose is
recommended.
Anthracycline-induced
cardiomyopathy was reported in one patient, and, therefore, echocardiographic
monitoring is recommended.
Systematic monitoring, particularly of the haematological response,
and supportive care are also essential during the treatment.
Magnetic Resonance
Imaging (MRI)
and ultrasonography are the methods of choice when imaging studies are
necessary.
Cranial MRI may reveal central nervous system developmental abnormalities and solid tumours. MRI
of chest and abdomen/pelvis allows the identification of a tumour mass.
Ultrasonography of the abdomen depicts urinary tract abnormalities, multiple or
accessory spleens, and enlarged lymph nodes. Pelvic ultrasonography in females can demonstrate small homoechoic
ovaries resembling streaks and an infantile uterus.
Surgical
correction of malformations (e.g. anal atresia, polydactyly) and treatment of
hydrocephaly can be necessary.
Delayed
or absent sexual maturation must be monitored, especially in females, and an
endocrinological evaluation
of the pituitary-gonadal axis
is recommended. When
ovarian
failure/hypergonadotrophic hypogonadism is confirmed,
substitution hormonal therapy should be considered when the patient
reaches the appropriate age.
Periodic follow-up is
also
indicated
in
all patients to
monitor physical growth.
Neuropsychiatric
and educational support may be required and speech therapy is needed to
improve language development and to correct articulation problems.
Because
of chromosome instability, Vitamin E and folic acid supplementation, in doses
appropriate for body weight, is recommended.
No
specific therapy for NBS exists.
Page last updated on: 18th May 2007