Fanconi Syndrome in an Adolescent Male

Introduction: In the pediatric population, Fanconi Syndrome often has a clear etiology and is usually inherited or acquired. Inherited cases are secondary to in-born errors of metabolism and present in early life in the majority of cases. Acquired causes usually have an identified trigger such as drug or metal exposure. We present the case of an adolescent male with Fanconi Syndrome secondary to tubulointerstitial nephritis with uveitis (TINU) and highlight the importance of recognizing ocular involvement.

Case Description: A previously healthy 14-year-old male presented with a 2-week history of nausea and diffuse “stabbing” intermittent abdominal pain worse with meals, associated occasionally with non-bloody, non-bilious emesis. He endorsed fatigue, poor appetite, and 20lbs of unintentional weight loss over the past month. Review of systems negative for fever, lymphadenopathy, night-sweats, or hematuria. No sick contacts, recent travel, or drug use. Lab work revealed normal sodium level (140 mmol/L), hyperchloremia (Cl: 111 mmol/L), hypokalemia (K: 3.4 mmol/L), elevated BUN (36 mg/dL) and creatinine (4.63 mg/dL), low bicarbonate (17mmol/L) with normal anion gap. CBC with normocytic anemia (Hgb 10.8 g/dL). Inflammatory markers elevated with ESR (94) and CRP (4.6 mg/dL). Urinalysis with glucosuria, proteinuria and protein/creatinine ratio of 1,289 mg/g. Given hyperchloremic, hypokalemic, metabolic acidosis with glucosuria and proteinuria, patient was diagnosed with Fanconi Syndrome. Urinary β2-Microglobulin (β2M) elevated to 21,041 mcg/L (normal <190) suggestive of tubular proteinuria. Renal biopsy revealed acute diffuse tubulointerstitial nephritis (TIN). Etiology of the tubulointerstitial nephritis was unrevealing: negative ANA panel, negative infectious disease work-up (EBV, TB, Histoplasmosis) and no history of chronic NSAID use. Patient’s slit lamp exam was negative for uveitis, but he presented with eye pain and vision changes two months after diagnosis.

Discussion: TINU is an underdiagnosed reno-ocular syndrome presenting with renal failure, accompanied by signs of tubular dysfunction and elevated inflammatory markers. The median age at diagnosis is 15 years. Fanconi syndrome is a unique finding in our patient and represents the totality and extent of tubular damage he experienced. Although renal biopsy in the gold standard for diagnosis, elevated β2M with elevated serum creatinine have shown significant positive predictive value. Uveitis can present 2 months prior to renal symptoms and up to 14 months after. Management includes supportive care with correction of electrolyte disturbances. Steroids are used in cases of persistently elevated creatinine, otherwise most cases improve without intervention. Although renal function recovers in the majority of cases, uveitis can become chronic.

Conclusion: Fanconi Syndrome is a rare finding in the adolescent population. In the pediatric patient with elevated creatinine, TINU should be suspected if there are signs of diffuse tubular dysfunction, such as Fanconi Syndrome. Our case highlights the importance of correctly recognizing TINU to allow for appropriate ophthalmology evaluation and follow-up.