Background: LPS-responsive beige-like anchor protein(LRBA) deficiency is an autosomal recessive disorder caused by biallelic mutations in the LRBA gene leading to a syndrome of autoimmunity, lymphoproliferation and humoral immune deficiency.LRBA protein plays a major immuno-regulatory role in the expression, function and trafficking of cytotoxic T lymphocyte-associated protein 4 (CTLA4) in Tregs which is an immune effector molecule that acts as an inhibitory checkpoint for the immune response. ^1,2,3

Objectives: We report a 7 years old boy with LRBA deficiency who was presented with polyautoimmuity primarily affecting gut, pancreas & joints with recurrent infections.

Methods: He was born to a non-consanguineous Indian parents with uneventful birth, development and vaccination history.He had been unwell from the age of one with multiple episodes of lower respiratory tract infections warranting usage of prolonged antibiotics. 2.5 years of age, he had been diagnosed as Type 1 Diabetes Mellitus and he was commenced on insulin therapy. 3.5 years, he developed chronic diarrhoea.Evaluation revealed sterile blood, urine and stool cultures with normal abdominal imaging(USG & CT scan), elevated TTg-IgA & HTTP/DGP screen and negative HLADQ2-DQ8. He failed gluten-free diet. Gastrointestinal endoscopy showed duodenum and terminal ileum nodularity & biopsy was suggestive of non-celiac autoimmune enteropathy. 4 years, he developed two episodes of stridor, tetany and breathing difficulty which were promptly reversed by IV calcium infusion. He had low serum calcium, low parathyroid hormone with normal vitamin D level, serum phosphorous, magnesium, thyroid profile, anti-thyroid antibodies, renal and liver functions. 5.5 years, he first presented to us with chronic unexplained polyarthritis involving small and large joints in an additive pattern. Family history was significant for a death of the previous male sibling at 7 months of age due to chronic unexplained diarrhoea. Examination revealed facial dysmorphism and failure to thrive with no systmic findings.

Results: Investigations showed HB 8.1gm%,TLC6700/cumm with normal differential counts and platelet counts 233000/ul. ESR was 39mm/hr and CRP was negative. Direct coomb’s test, RF, ANA were negative. He had a mild elevation in IgG levels with normal B-T cells populations. Genetic evaluation revelaed pathogenic homozygous splice site mutation in intron 11 of LRBA gene. Both the parents are heterozygous carriers. A largest systematic review ³ of 212 cases of LRBA deficiency showed autoimmunity(70%), non malignanat lymphoproliferation(54%), enteropathy(41%), endocrinopathy(41%) and lower respiratory tract infections(41%) as the most common clinical manifestations with normal or abnormal immunoglobulin level and B-T cells populations. Arthritis(8%) was amongst the rare manifestations. Hypoparathyroidism was the rarest endocrine manifestations. No data available regarding prevalence of positive celiac disease antibodies. There was no haematological manifestations in our case.

Conclusion: LRBA deficiency should be strongly considered in a child recurrent infection and polyautoimmunity including arthritis. Abatacept could be used as a steroid sparing agent and as a bridging agent awaiting transplant.

REFERENCES:

[1]Am J Hum Genet.2012; Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Lopez-Herrera G, Tampella G, Hammarström Q, et al.

[2]J Allergy Clin Immunol Pract Sep-Oct 2019; Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review Sima Habibi, Majid Zaki-Dizaji, Hosein Rafiemanesh, Bernice Lo, Mahnaz Jamee

[3]Clinical and Experimental Immunology, 31 ^st March 2021, Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review, M. Jamee, S. Hosseinzadeh, N. Sharifinejad, M. Zaki-Dizaji

Acknowledgements: Dr Hitesh Bhambhani, Dr Nitin Trivedi, Dr Zalak Shah Upadhyay, Dr Chetan Dave

Disclosure of Interests: None declared