Background and Aims

Background

LPS Responsive Beige like Anchor Protein (LRBA) is a BEACH Domain Containing Protein that was first fully cloned in mouse and human in 2001. LRBA mRNA is expressed in almost all cell types with an elevated expression in immune cells. LRBA deficient patients have inadequate proliferation of B cells and defective autophagy resulting in hypogammaglobulinemia and autoimmunity. Here we present the first Indian cohort of LRBA deficiency.

Methods

Clinical and immunological phenotype, therapeutic approach and outcome of 3 patients from 3 different families were assessed retrospectively in this study.

Results

Demographics: Age of first symptom varied from 10 months for homozygous mutation to average of 4 years for the heterozygous one. All patients had autoimmune cytopenias with age of onset around 3 years of age.Clinical phenotype: The most common clinical manifestations was organomegaly and autoimmunity. Autoimmunity mainly presented as immune mediated cytopenia. One child had family history of autoimmunity. One patient had insulin dependent diabetes mellitus with celiac disease.Infectious profile: All patients had at least one documented infectious episode. 2 episodes of viral infections were seen, EBV and severe chickenpox.Immunological phenotype:The only non-immunosuppressed patient had a normal lymphocyte subset analysis. All 3 patients had a normal immunoglobulin assay at presentation, one child developed hypogammaglobulinemia after rituximab. Therapeutic Approach:As abatacept is too costly and non-affordable in our patient cohort we used sirolimus for all 3 patients. All children have no side effects to sirolimus therapy so far. None of them have undergone HSCT.

Conclusions

Sirolimus can be effective as single drug with good disease control in LRBA deficiency.

Background and Aims

CARD protein–BCL-10–MALT1 (CBM) signalosomes are signalling complexes involved in NF KB activation. Defects in MALT1, CARD9 and CARD 11 have been described. There is only one reported case in literature of Bcl 10 deficiency. We present a child with a nonsense mutation in Bcl10 resulting in premature truncation of the protein.

Methods

Materials and method- Retrospectively analysis of a patient diagnosed as Bcl10 deficiency was analysed.

Results

6 month old boy, born of 3^rd degree consanguineous marriage with history of sibling death was referred post an intensive care admission for viral lower respiratory tract infection with palatal ulcers.A baseline immune workup showed normal lymphocyte subsets including naïve T cells and low Ig G, A and M.A differential of transient hypogammaglobulinemia of infancy was considered.On follow up, he maintained a good IgG level without replacement.

At 11 months of age, he had fever with sudden onset respiratory distress. On examination, he was tachypnoeic, maintain saturations on O2 by nasal cannula and had bilateral crepts. Evaluation showed eosinophilia and bilateral infiltrates on the chest Xray.BAL was positive for galactomannan, chest CT didn’t show any evidence of fungal infection. He was started on voriconazole with complete recovery. Next generation sequencing showed a homozygous nonsense variation in exon 2 of the BCL10 gene (chr1:85736385G>A) that resulted in a stop codon and premature truncation of the protein at codon 88. On follow up, he developed a flare of the BCG scar.

Conclusions

BCL10 and MALT 1 phenotype described include susceptibility to fungal, bacterial and viral infections as seen in our patient.

Background and Aims

Enterovirus encephalitis has been described in patients with agammaglobulinemia since 1961.It can occur even with adequate immunoglobulin replacement as there can be great variation in antibody titres against circulating enterovirus serotypes.Lack of specific therapy and delay in diagnosis contribute to the poor outcome. We present two patients managed at our centre in collaboration with Great Ormond Street Hospital with near complete recovery.

Aims- Retrospective analysis of clinical manifestations, management and outcome in two agammaglobulinemic patients diagnosed with enterovirus encephalitis.

Methods

2 patients from 2 different families with enterovirus encephalitis while on immunoglobulin replacement therapy were retrospectively analysed.

Results

Patient 1- 3 ½ year old girl on ivig for agammaglobulinemia developed subacute onset of drowsiness.CSF showed pleocytosis, enterovirus detected by PCR and MRI was suggestive of meningoencephalitis.She had persistence of enterovirus in CSF, developed status epilepticus 6 months later with rapid neurological deterioration. A trial of ribavirin and fluoxetine with high dose ivig resulted in clinical improvement within a month.She regained most of her milestones with improvement in MRI changes and CSF pleocytosis but developed orthostatic tremors during a year of follow up.Patient 2- 5 year old boy diagnosed as XLA, on immunoglobulin replacement therapy presented with acute onset encephalopathy with CSF pleocytosis and enterovirus detected by PCR.He was started on fluoxetine and ivig at first presentation.Within 3 months of treatment all symptoms had resolved except left arm paresis.

Conclusions

Fluoxetine and ribavirin have antiviral activity against enterovirus and are easily available. Early treatment with high dose ivig and antivirals may have better outcomes.