DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20203185

Scrub typhus leading to focal segmental glomerulosclerosis in a child due to genetic predisposition

Shreyasi Das, Rajendra Pandey, Sumit Roy

Abstract


Scrub typhus is a multisystem disease, caused by genera orientia tsutsugamushi and is currently endemic in India. In children, the disease may vary from a mild to a severe form. Complications include encephalitis, myocarditis, disseminated intravascular coagulation, acute kidney injury, atypical pneumonia, etc. The pathophysiologic mechanisms of renal involvement in scrub typhus include prerenal failure, septic shock, vasculitis, acute tubular injury and direct renal invasion by rickettsia. Here, authors present the case of a previously well 5-year old female child who was admitted to our hospital with a history of high-grade fever and pain abdomen. IgM scrub typhus turned out to be positive and she was adequately treated with doxycycline. She turned afebrile but then gradually developed anasarca, hematuria, proteinuria and persistent stage 2 hypertension. Kidney biopsy was done which revealed focal segmental glomerulosclerosis (FSGS). Further workup of the patient by whole exome sequencing revealed missense mutations in TBX18, INF2 and NPHS1 genes. Mutations in INF2 gene is a recently discovered cause of autosomal dominant FSGS. In our case, the scrub typhus mediated kidney injury probably acted as a trigger in unmasking FSGS in the already genetically susceptible child.


Keywords


Focal segmental glomerulosclerosis, Genetic mutations, INF2 mutation, Scrub typhus

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References


Jamil MD, Lyngrah KG, Lyngdoh M, Hussain M. Clinical manifestations and complications of scrub typhus: a hospital based study from north eastern India. J Assoc Physicians India. 2014;62(12):19-23.

Palanivel S, Nedunchelian K, Poovazhagi V, Raghunadan R, Ramachandran P. Clinical profile of scrub typhus in children. Indian J Pediatr. 2012 Nov 1;79(11):1459-62.

Kim DE, Lee SH, Park KI, Chang KH, Roh JK. Scrub typhus encephalomyelitis with prominent focal neurologic signs. Arch Neurol. 2000;57(12):1770-2.

Kumar V, Kumar V, Yadav AK, Iyengar S, Bhalla A, Sharma N, et al. Scrub typhus is an under-recognized cause of acute febrile illness with acute kidney injury in India. PLoS Neglected Tropical Dis. 2014 Jan;8(1).

Lee JH, Lee MJ, Shin DH, Kang SW, Choi KH, Yoo TH. A case of Tsutsugamushi disease presenting with nephrotic syndrome. Korean J Internal Med. 2013;28(6):728.

Wiggins RC. The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int. 2007;71(12):1205-14.

Sharma A, Mahajan S, Gupta ML, Kanga A, Sharma V. Investigation of an outbreak of scrub typhus in the Himalayan region of India. Japanese J Inf Dis. 2005;58(4):208.

Kumar M, Krishnamurthy S, Delhikumar CG, Narayanan P, Biswal N, Srinivasan S. Scrub typhus in children at a tertiary hospital in southern India: clinical profile and complications. J Infe Public Health. 2012;5(1):82-8.

Young PC, Hae CC, Lee KH, Hoon CJ. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure. Korean J Int Med. 2003;18(4):248.

Kim DM, Kang DW, Kim JO, Chung JH, Kim HL, Park CY, et al. Acute renal failure due to acute tubular necrosis caused by direct invasion of Orientia tsutsugamushi. J Clin Microbiol. 2008;46(4):1548-50.

Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soci Nephrol. 2007;2(3):529-42.

Morgan C, Al-Aklabi M, Guerra GG. Chronic kidney disease in congenital heart disease patients: a narrative review of evidence. Canadian J Kidney Health Dis. 2015;2:63.

Aygun B, Mortier NA, Smeltzer MP, Hankins JS, Ware RE. Glomerular hyperfiltration and albuminuria in children with sickle cell anemia. Pediatric Nephrol. 2011;26(8):1285-90.

Wickman C, Kramer H. Obesity and kidney disease: potential mechanisms. InSeminars in Nephrol. 2013;33(1):14-22.

Brown EJ, Schlöndorff JS, Becker DJ, Tsukaguchi H, Tonna SJ, Uscinski AL, et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nature Genetics. 2010;42(1):72-6.

Barua M, Brown EJ, Charoonratana VT, Genovese G, Sun H, Pollak MR. Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. Kidney Int. 2013;83(2):316-22.

Boyer O, Benoit G, Gribouval O, Nevo F, TĂȘte MJ, Dantal J, et al. Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis. J Am Soc Nephrol. 2011;22(2):239-45.

Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int. 1998;54(3):687-97.