A puzzling renal Fanconi syndrome.

Area of Science:

• Genetics
• Nephrology
• Molecular Biology

Background:

• Renal Fanconi syndrome (FS) is a kidney tubule disorder that can be inherited or acquired.
• Inherited FS presenting in childhood is most commonly caused by cystinosis.
• Autosomal dominant Fanconi syndrome type 3 (FRTS3) is a rare inherited form of FS.

Observation:

• This report details a family with autosomal dominant FRTS3 caused by a previously identified heterozygous p.E3K variant in the EHHADH gene.
• Previous reports indicated normal or minimally impaired kidney function in late life for FRTS3 patients.
• This family exhibited a wider spectrum of disease severity, including isolated glucosuria and proteinuria, and complete Fanconi syndrome with rickets.

Findings:

• The study expands the known phenotypic spectrum of FRTS3.
• Individuals presented with varying degrees of kidney tubule dysfunction.
• Crucially, the proband demonstrated impaired kidney function at a young age, suggesting earlier disease onset is possible.

Implications:

• This expands the clinical understanding of Fanconi renotubular syndrome type 3.
• Early identification of kidney function impairment in FRTS3 is possible.
• The findings highlight the importance of genetic analysis for diagnosing inherited kidney diseases with variable presentations.