Chronic Benign Tubular Albuminuria From Compound Heterozygous Variants in CUBN: A Case Report

Area of Science:

• Nephrology
• Genetics
• Molecular Biology

Background:

• Albuminuria often indicates declining kidney function.
• Cubilin (CUBN) protein is crucial for reabsorption in kidney tubules.
• CUBN mutations cause Imerslund-Gräsbeck syndrome (IGS), linked to vitamin B12 deficiency and sometimes albuminuria.

Purpose of the Study:

• To investigate a case of chronic albuminuria with preserved kidney function.
• To identify the genetic basis of the patient's condition.
• To understand the relationship between CUBN variants and albuminuria phenotypes.

Main Methods:

• Case report of a 52-year-old male with persistent albuminuria.
• Genetic testing for CUBN gene variants.
• Segregation analysis to confirm inheritance patterns.

Main Results:

• The patient presented with chronic, albumin-predominant proteinuria and normal estimated glomerular filtration rate (eGFR).
• Genetic testing revealed compound heterozygous pathogenic variants in CUBN, located downstream of the vitamin B12 binding domain.
• The patient had normal vitamin B12 levels and no IGS features.

Conclusions:

• Albuminuria can arise from tubular defects due to CUBN variants, independent of kidney filtration decline.
• Genetic testing for CUBN is crucial for accurate diagnosis and to guide treatment, avoiding ineffective therapies like ACE inhibitors or AT-II receptor blockers.
• C-terminal CUBN variants are associated with albuminuria without vitamin B12 deficiency, distinguishing them from classic IGS.