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Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency

Orpha number ORPHA319558
Synonym(s) MSMD due to complete IL12B deficiency
MSMD due to complete interleukin 12B deficiency
Mendelian susceptibility to mycobacterial diseases due to complete interleukin 12B deficiency
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Infancy
Neonatal
ICD-10
  • D84.8
ICD-O -
OMIM
UMLS -
MeSH -
MedDRA -

Summary

Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 subunit beta (IL12B) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.

The prevalence is unknown. Mutations have been found in 49 patients from 30 kindreds originating from India, Iran, Pakistan, Saudi Arabia and Tunisia.

The disease presents in early childhood. BCG is the most common infection encountered, usually after receiving the vaccination. Non-typhoidal Salmonella infections are also seen in half of all cases. A few other infections have been reported, including chronic mucocutaneous candidiasis (CMC), nocardiosis, and klebsiellosis. An incomplete clinical penetrance is observed in this immunodeficiency.

MSMD due to complete IL12B deficiency is caused by homozygous mutations in the IL12B gene on chromosome 5q31.1-q33.1 which encodes for the IL-12p40 subunit. There are 9 different IL12B mutant alleles identified, including 2 small insertions, 3 small deletions, 2 splice site mutations, 1 large deletion and 1 nonsense mutation.

Diagnosis is made by laboratory analysis. IFN-gamma, IL-12p40 and IL-12p70 levels can be measured by ELISA after whole blood activation by BCG, BCG+IL-12 and BCG+IFN-gamma. The patients lack detectable IL-12p70, IL-12p40 and produce low levels of IFN-gamma. Genetic testing reveals mutations in IL12B.

Differential diagnoses include other genetic forms of MSMD, especially MSMD due to complete IL12RB1 deficiency (see this term).

This immunodeficiency is not severe and antenatal diagnosis is not necessary.

MSMD due to complete IL12B deficiency is inherited in an autosomal recessive manner. Genetic counseling is possible for families where a IL12B mutation is known.

BCG vaccination should be avoided in patients with this disease. Treatment involves prolonged antimicrobial therapy along with recombinant IFN-gamma to control infections, which is successful in most cases. Hematopoietic stem cell (HST) transplantation is not recommended.

Patients with this immunodeficiency usually have a good prognosis.

Expert reviewer(s)

  • Dr Jacinta BUSTAMANTE
  • Pr Jean-Laurent CASANOVA

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