Background and Aims

Chronic Granulomatous Disease (CGD) is a well – known form of Primary Immune Deficiency Disorders (PIDD) where the neutrophils fails to perform intracellular killing of the organisms. These patients are highly susceptible to infections due to catalase +ve bacteria, Mycobacteria and fungal infection and Autoimmunity. They develop cutaneous as well as deep seated infections. CGD usually diagnosed by performing NBT test or more accurate OXIDATIVE BURST and we need genetic testing rarely. CGD is due to mutation in the different components:

Although Rare types of CGD might be associated with Normal Oxidative burst. In this case high clinical suspension should be confirmed by molecular genetic testing.

Methods

This is a case series report, the Index case was a 12 years old brother who has recurrent infections and Autoimmunity diagnosed by PID panel requested after the diagnosis of CGD

PID panel sent for the rest of the family members found in another 2 siblings a boy and a girl.

Results

Oxidative burst was either normal or near normal in this family.

The PID panel showed the following mutation:

Variant: NCF4:NM_000631:exon5:c.407C>A:p.S136X -- (HOMOZYGOUS)

Strikingly that this family with CGD due to mutation in the P40 component of NADPH.

Conclusions

High clinical suspicion of Primary immune deficiency should warrant molecular genetic testing especially when routine immunological workup fail short to help in the diagnosis and thus treatment. Here we report a rare form of CGD were the gold standard test for diagnosis is oxidative burst was Normal or near normal.

Background and Aims

Autoimmune LymphoProliferative Syndrome (ALPS) is a rare autosomal dominant disorder characterized by inability to regulate lymphocyte homeostasis, resulting from a defect in lymphocyte apoptosis (programmed cell death).

Defective Apoptosis may be due to any component in the Fas/FasL pathway including: Fas, Fas Ligand, and Caspase enzymes like caspase 10 and others.

Our aim is to present a case of ALPS, which underline the importance of the molecular diagnosis in Primary Immune Deficiency Patients.

Methods

15 Year old boy with clinical diagnosis of Common variable immunodeficiency (CVID). With the following previous histories:

- Immune thrombocytopenic purpura (ITP) s/p rituximab 3 years ago.

- Crohn’s disease (CD). Diagnosed by Endoscopy and pathology report.

- Short stature. with No signs of Puberty

Acutely presented to our ER with history of increased diarrhea and shortness of breath.

Upon presentation patient was short, Pale, dehydrated and hypotensive with tachycardic and hypoxic, BMI: 10 kg/m2. His sexual staging was Tanner stage 1

CMV PCR was positive of 1,584.

Patient was started on ganciclovir. No CMV retinitis.

Colonoscopy: tiny ulcers in the distal rectum.

Intestinal Biopsies: SEVERE ACTIVE ULCERATIVE CYTOMEGALOVIRUS (CMV) PROCTITIS.

Results

Immunology workup: IgA level is low (<0.50), IgM level low (<0.25) also IgG trough level was low <3

Molecular Report: mutation in the gene encoding the Caspase 8 enzyme, which means he is a case of ALPS.

Conclusions

ALPS is a very rare disease can easily be confused with CVID , with recent advances in molecular genetics diagnosis, treatment options and prognosis improving for such patients.