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Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis

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Abstract

Background

Myelin figures, or zebra bodies, seen on electron microscopy were historically considered pathognomonic of Fabry disease, a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency and associated with X-linked recessive mode of inheritance. More recently, iatrogenic phospholipidosis has emerged as an important alternate cause of myelin figures in the kidney.

Methods

We report two families with autosomal dominant nephropathy presenting with proteinuria and microscopic hematuria, and the kidney biopsies were notable for the presence of myelin figures and zebra bodies.

Results

Laboratory and genetic work-up for Fabry disease was negative. Genetic testing in both families revealed the same heterozygous missense mutation in LMX1B (C.737G>A, p.Arg246Gln). LMX1B mutations are known to cause nail-patella syndrome, featuring dysplastic nails and patella with or without nephropathy, as well as isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations.

Conclusions

LMX1B mutation-associated nephropathy should be considered in hereditary cases of proteinuria and/or hematuria, even in the absence of unique glomerular basement membrane changes indicative of nail-patella syndrome. In addition, LMX1B mutation should be included in the differential diagnosis of myelin figures and zebra bodies on kidney biopsy, so as to avoid a misdiagnosis.

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Acknowledgements

The authors would like to thank Ms. Ivy L. Liu for her help with Figure 1.

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Author notes

  1. Li Lei and Gia Oh contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Stanford University, H2110, 300 Pasteur Drive, Stanford, CA, 94305, USA

    Li Lei, John Higgins, Richard Sibley, Megan Troxell & Neeraja Kambham

  2. Randall Children’s Hospital, Portland, OR, USA

    Gia Oh

  3. Department of Pediatrics & Division of Nephrology, Stanford University, Stanford, CA, USA

    Scott Sutherland

  4. Satellite Healthcare, San Jose, CA, USA

    Graham Abra

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  1. Li Lei
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Correspondence to Neeraja Kambham.

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Lei, L., Oh, G., Sutherland, S. et al. Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis. Pediatr Nephrol 35, 1647–1657 (2020). https://doi.org/10.1007/s00467-020-04564-w

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  • DOI: https://doi.org/10.1007/s00467-020-04564-w

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