A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome

• Published in: Pediatric nephrology (Berlin, West) Vol. 27; no. 5; pp. 869 - 872
• Main Authors: Lee, Joyce J., Tripi, Laura M., Erbe, Richard W., Garimella-Krovi, Sudha, Springate, James E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-05-2012; Springer; Springer Nature B.V
• Subjects: Acid-Base Imbalance - etiology; Acidosis; Acidosis - complications; Bicarbonate; Bicarbonates - therapeutic use; Blood; Brief Report; Carbonates; Child, Preschool; Cornea; Corneal dystrophy; Corneal Opacity - etiology; Corneal Opacity - genetics; DNA, Mitochondrial - genetics; Drug Resistance; Electron transport; Etiology; Fanconi syndrome; Fanconi Syndrome - complications; Fanconi Syndrome - genetics; Female; Genetic screening; Genetic testing; Glucose; Hearing Loss, Sensorineural - etiology; Humans; Intravenous administration; Kidney Function Tests; Lactic acid; Leukocytes; Medical screening; Medicine; Medicine & Public Health; Metabolism; Mitochondria; Mitochondrial Diseases - complications; Mitochondrial Diseases - genetics; Mitochondrial DNA; Nephrology; Organic acids; Patients; Pediatrics; Photophobia - etiology; Pyruvic acid; Sequence Deletion; Supplementation; Transplants & implants; Uric acid; Urine; Urology; Weight Loss; Mitochondrial DNA deletion; Fanconi syndrome; Corneal dystrophy; Mitochondrial disease; Metabolic acidosis
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-011-2096-2

Background
Mitochondrial cytopathies are a diverse group of disorders characterized by impaired mitochondrial energy production. Disease manifestations are protean and may include seemingly disparate findings.
Case Diagnosis/Treatment
Here we report a 5-year-old girl with the uncommon pairing of bilateral corneal dystrophy requiring corneal transplantation and severe Fanconi syndrome recalcitrant to oral bicarbonate therapy necessitating intravenous supplementation. Etiological work-up included qualitative urine organic acid testing, which demonstrated abnormalities in lactate, pyruvate, and ketoacids suggestive of a mitochondrial etiology. Confirmatory genetic testing in blood leukocytes revealed a large, novel, heteroplasmic, de novo mitochondrial DNA deletion at nt 8648–16072.
Conclusion
The finding of Fanconi syndrome with disease processes in other, seemingly unrelated, organ systems should raise clinical suspicion for mitochondrial disease. Early assessment of urine organic acids in the etiological work-up of Fanconi syndrome may assist in the identification of respiratory chain disorders.