Another Case of Mitochondriopathy Manifesting as Inherited Tubulointerstitial Nephropathy without Other Symptomatic Organ Involvement

To the Editor

We read with great interest the case report of Buglioni et al.,¹ and report a similar one.

A 27-year-old man presented with mild kidney impairment (creatinine serum level 1.6 mg/dl, estimated glomereular filtration rate 55 ml/min per 1.73 m²) and low-grade proteinuria (0.25 g/d) without hematuria or leucocyturia. Workup revealed high creatinine kinase levels (700 UI/L, N < 200) and an HbA1C level of 6.2%. Renal ultrasound showed normal-sized kidneys. A kidney biopsy specimen showed mild, nonspecific, chronic tubulointerstitial nephritis by light microscopy and an absence of immune deposits by immunofluorescence.

The patient’s family history was positive. His 23-year old sister had been diagnosed with type 2 diabetes with microalbuminuria, and his mother had developed gestational diabetes at age 32 years (Figure 1) with normal kidney function. Autosomal dominant tubulo-interstitial kidney disease (ADTKD)−TCF2 mutations were ruled out in the patient. Next-generation sequencing of the entire mitochondrial genome was then performed on a urine sample, showing an m.3243A>G point mutation in the mitochondrial-encoded MTTL1 gene, the most common cause of mitochondrial disease. Patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome have a highly variable phenotype, ranging from isolated diabetes and deafness to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (OMIM #540000).² In MELAS syndrome, kidney involvement in rare and is usually associated with a focal segmental glomerulosclerosis pattern of injury. The m.3243A>G heteroplasmy was 31% and 88% in the patient’s blood and urine samples, respectively, and 19% in his sister’s blood sample. Urinary epithelium shows the most consistent mutation load for initial diagnosis.³

Figure 1.

Patient’s family tree. CKD, chronic kidney disease.

Both cases highlight the clinical relevance of including mitochondrial diseases in the differential diagnosis of tubulo-interstitial disease in young patients, even with no or mild extrarenal manifestations.