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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 2  |  Page : 97-98

Chronic kidney disease in a patient with large platelets and hearing loss

1 Division of Pediatric Nephrology, Department of Child Health, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Immunohematology and Transfusion Medicine, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission23-Oct-2022
Date of Decision19-Nov-2022
Date of Acceptance19-Nov-2022
Date of Web Publication31-Dec-2022

Correspondence Address:
Georgie Mathew
Division of Pediatric Nephrology, Department of Child Health, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Mathew G, Gnanaraj J, Nair SC, Raranveettil D. Chronic kidney disease in a patient with large platelets and hearing loss. Asian J Pediatr Nephrol 2022;5:97-8

How to cite this URL:
Mathew G, Gnanaraj J, Nair SC, Raranveettil D. Chronic kidney disease in a patient with large platelets and hearing loss. Asian J Pediatr Nephrol [serial online] 2022 [cited 2023 Mar 24];5:97-8. Available from: https://www.ajpn-online.org/text.asp?2022/5/2/97/366541


A 15-year-old boy presented with foamy urine for the preceding 2 months, without any hematuria or edema. There was no history of fever, rash, joint pain, poor growth, recurrent transfusions, and family history was negative for kidney disease. Persistent thrombocytopenia (range 15,000-90,000/mm3) without any bleeding diathesis was reported in childhood, and the bone marrow was normocellular with increased megakaryocytes and flow cytometry reported negative for leukemia. He was advised to carefully monitor for any bleeding and was not prescribed any therapy. The evaluation showed urine protein-to-creatinine ratio of 7.5 mg/mg, serum albumin of 3.7 g/dL, and estimated glomerular filtration rate (eGFR) of 38 ml/min/1.73 m2. Urine examination was negative for red cells or active sediments. Peripheral smear demonstrated giant platelets which were larger than erythrocytes, along with neutrophils containing Döhle-like inclusion bodies [Figure 1]. Platelet counts were 60,000 per/mm3 with hemoglobin of 11.5 g/dL, with normal liver function tests. Kidney biopsy was suggestive of focal segmental glomerulosclerosis (FSGS). Ultrastructural examination showed 60% foot process effacement without any inclusion bodies or electron-dense deposits. Hearing assessment revealed bilateral moderate sensorineural hearing loss, and eye examination showed myopia, without any cataracts. Clinical exome testing revealed a pathogenic variant in the MYH9 gene (c.2104C>T; p.Arg702Cys). A diagnosis of MYH9-related disease was made, with features of FSGS,  May-Hegglin anomaly More Details, and sensorineural hearing loss. Sanger sequencing and segregation analysis were advised but not performed. Peripheral smear of his father was negative for features of MYH9-related disease, and his mother was not available for screening. Management for chronic kidney disease was initiated, and his family was counseled regarding the need of renal replacement therapy in the future. At 12 months of follow-up, his eGFR had declined to 17 ml/min/1.73 m2 without any triggering events for rapid decline such as episodes of acute kidney injury, and the patient is on conservative management.
Figure 1: Peripheral blood smear (×100, modified Wright Giemsa stain) demonstrates giant platelets which were larger than erythrocytes (arrowheads) along with neutrophils containing Döhle-like inclusion bodies (white arrow)

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MYH9-related disorders encompass phenotypes previously known as Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, Sebastian syndrome (Sebastian platelet syndrome), and autosomal dominant deafness 17 (DFNA17). These disorders are characterized by macrothrombocytopenia, with associated varying phenotypes of sensorineural hearing loss and glomerular and ocular involvement. Large platelets and thrombocytopenia are almost universal, with a tendency to bleed in 80%–90% cases after major surgery, delivery, or antiplatelet therapy; ~30% cases have spontaneous bleeds.[1] Döhle-like inclusion bodies are found in the neutrophils; identified by the May-Grünwald-Giemsa stain or as nonmuscle myosin heavy chain IIA (NMMHC-IIA) by immunofluorescence.[2] Sensorineural hearing loss is observed in about half of the affected patients and is usually progressive.[3] Other findings include elevated liver enzymes and cataracts.

Kidney involvement is heterogeneous, occurring in 25%–90% of involved patients, with nearly 60% reaching end-stage kidney disease in the second-third decades of life.[1],[4] FSGS is the common pathology observed. MYH9 codes for the heavy chain of the NMMHC-IIA, a protein found in the podocyte, inner ear hair cell, and other cells. The phenotype of the p.Arg702Cys variant, affecting the globular head domain , is reported as a very severe phenotype.[2],[5] Alport syndrome is a close differential diagnosis when platelet counts are normal.

Clinicians, pathologists, and pediatric nephrologists should keenly look for unexplained thrombocytopenia in children with chronic kidney disease or proteinuria. The inputs from a keen observation of a peripheral smear are valuable to the diagnosis. Genetic analysis will help in diagnosing this specific disorder and facilitate screening of other family members in this autosomal dominant disorder.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Pecci A, Klersy C, Gresele P, Lee KJ, De Rocco D, Bozzi V, et al. MYH9-related disease: A novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat 2014;35:236-47.  Back to cited text no. 1
Bury L, Megy K, Stephens JC, Grassi L, Greene D, Gleadall N, et al. Next-generation sequencing for the diagnosis of MYH9-RD: Predicting pathogenic variants. Hum Mutat 2020;41:277-90.  Back to cited text no. 2
Verver EJ, Topsakal V, Kunst HP, Huygen PL, Heller PG, Pujol-Moix N, et al. Nonmuscle myosin heavy chain IIA mutation predicts severity and progression of sensorineural hearing loss in patients with MYH9-related disease. Ear Hear 2016;37:112-20.  Back to cited text no. 3
Tabibzadeh N, Fleury D, Labatut D, Bridoux F, Lionet A, Jourde-Chiche N, et al. MYH9-related disorders display heterogeneous kidney involvement and outcome. Clin Kidney J 2019;12:494-502.  Back to cited text no. 4
Saposnik B, Binard S, Fenneteau O, Nurden A, Nurden P, Hurtaud-Roux MF, et al. Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-related disorders. Mol Genet Genomic Med 2014;2:297-312.  Back to cited text no. 5


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