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Updated: Dec 22, 2025
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Published on: July 19, 2019
Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis
Li Lei1, Gia Oh2, Scott Sutherland3
1Department of Pathology, Stanford University, H2110, 300 Pasteur Drive, Stanford, CA, 94305, USA.
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.
Insights
Myelin figures in kidney biopsies can indicate Fabry disease or LMX1B-associated nephropathy. Genetic testing revealed LMX1B mutations in families with hereditary nephropathy, highlighting its importance in differential diagnosis.
Area of Science:
- Nephrology
- Genetics
- Pathology
Background:
- Myelin figures (zebra bodies) on kidney biopsy were historically linked to Fabry disease.
- Iatrogenic phospholipidosis is a recognized alternative cause of myelin figures in renal tissue.
Purpose of the Study:
- To investigate the cause of myelin figures in two families with hereditary nephropathy.
- To identify the genetic basis for autosomal dominant nephropathy presenting with proteinuria and hematuria.
Main Methods:
- Analysis of kidney biopsies showing myelin figures.
- Genetic testing for Fabry disease and LMX1B mutations.
- Clinical evaluation of affected families.
Main Results:
- Fabry disease testing was negative in both families.
- A heterozygous missense mutation in LMX1B (C.737G>A, p.Arg246Gln) was identified in all affected individuals.
- The mutation is associated with autosomal dominant nephropathy.
Conclusions:
- LMX1B-associated nephropathy should be considered in hereditary proteinuria/hematuria, even without classic nail-patella syndrome features.
- LMX1B mutations are a crucial differential diagnosis for myelin figures on kidney biopsy, preventing misdiagnosis of Fabry disease.
