Focal segmental glomerulosclerosis associated with mitochondrial disease

Area of Science:

• Genetics
• Nephrology
• Neurology

Background:

• Primary mitochondrial diseases (MD) are inherited disorders stemming from mutations in mitochondrial or nuclear DNA.
• Glomerular diseases have been previously linked to specific mitochondrial tRNA mutations, such as m.3243A>G, associated with MELAS syndrome.

Observation:

• A 34-year-old male with a history of kidney transplant, diabetes, hearing loss, and developmental delay presented with new behavioral issues and neurological decline.
• Physical examination revealed hearing impairment, dysarthric speech, and cerebellar gait. Initial laboratory tests, including lactate levels, were unremarkable.

Findings:

• Whole exome sequencing identified a novel mitochondrial MT-TW tRNA mutation at position m.5538G>A.
• Genotype-phenotype correlation supported this mutation as the cause of the patient's complex symptoms, including focal segmental glomerulosclerosis (FSGS).
• This is the first reported case of FSGS-associated MD caused by the m.5538 G>A mutation.

Implications:

• The findings highlight the importance of considering mitochondrial diseases in patients with a combination of deafness, neurological changes, diabetes, and renal failure.
• This case expands the known spectrum of renal manifestations in mitochondrial tRNA mutations.
• Early genetic investigation can aid in diagnosing complex cases of mitochondrial disease with renal involvement.