Dear colleagues,
We would like to initiate a multi-institutional survey of the CLINICAL PHENOTYPE of NEMO-deficient patients. We would like to invite you, as a physician caring for such patients, to take part in this survey.
Our hope is that the combined efforts of multiple institutions will allow us to define the clinical phenotype of this disease in more detail. This study could potentially facilitate the development of treatment guidelines for this heterogeneous genetic disorder.
We intend to publish the results of this survey in a clinical journal focusing on clinical hematology and immunology or pediatrics in the near future, to raise the awareness of clinicians concerning this condition.
NEMO-deficient patients have several features of special interest to us for the purposes of this survey (survey for download below):
1. EDA phenotype
About 90% of the NEMO-deficient patients described to date have EDA, with sparse hair, abnormal teeth (conical teeth, tooth agenesis) and hypohidrosis (a lack of sweating). Could you please provide us with a description of these abnormalities in your patients and their families?
2. Infection
Please provide clinical data for infections, as follows:
- Invasive bacterial infections (meningitis, sepsis, arthritis, deep inner abscesses)
- Opportunistic infections (pneumocystosis, chronic candidiasis etc.)
- Mycobacterial infections
- Severe viral infections
- Other infections
3.Signs of inflammation
a) Clinical signs
- Some patients develop a disseminated skin eruption, dermatitis, eczema and/or erythema early in life. Please provide a clinical and histological description of these conditions if observed in your patients.
- Colitis is also found in 21% of patients and some patients have intractable diarrhea with failure to thrive. Please indicate whether your patient displayed irritable bowel disease.
b) Biological signs
We would like to determine whether NEMO deficiency is a condition that predisposes the patient to the development of severe infections in a context of weak inflammation. We would therefore like to ask you, in particular, for:
- The date of onset of infectious episodes, as provided by the patient’s parents or guardians, and all dates of the analyses provided.
- Please provide at least three values for the following parameters: temperature, CrP, ESR, total white blood cell count and differential blood count. Please provide the values immediately after admission, the maximum value during the infectious episode and the value immediately before discharge.
4.Immunological status
a) T-cell immunophenotype and T-cell proliferation
The immunological parameters used for diagnosis, such as the numbers of blood phagocytes, B and T lymphocytes, lymphocyte subset distribution (CD4, CD8), T-cell proliferation in response to mitogens and antigens, are generally normal in most patients tested, but some patients have been reported to display weak T-cell proliferation in response to OKT3.
b) Specific antibody deficiency/ deficiency of antibodies against polysaccharides
Please provide information about antibody production (IgG, A, M and specific antibodies).
NEMO patients are unable to mount an adequate response to polysaccharides. Please provide us with information concerning the corresponding vaccinations (dates and vaccine used: 7-valent conjugated, 13-valent conjugated or 23-valent non conjugated?) and the results of serological tests for antibodies against polysaccharides. Please also state whether your patients have allohemagglutinins.
5. Treatment
Please provide as much detail about the treatments administered as possible (e.g. generic names of antibiotics, route of administration and duration of treatment). We would also like to know whether your patients have undergone transplantation and the details of the procedure if they have (conditioning regimens, donor, engraftment and outcome).
We would be delighted if you would agree to participate in this study, by completing the attached questionnaire, paying particular attention to the points of interest outlined above. If you have any further questions, please feel free to contact us under:
Laboratory of Human Genetics of Infectious Diseases
Faculté de Médecine Necker, 156 rue de Vaugirard
75730 Paris Cedex 15, France
Tel 33 1 44 49 50 88, Fax 33 1 42 73 06 40
E.mail capucine.picard@inserm.fr
With kind regards,
Capucine Picard, MD, PhD
Jordan Orange, MD, PhD
Jean-Laurent Casanova, MD, PhD
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