A 9-year-old boy is brought to the clinic for evaluation of dark brown urine for a day. He has had no fever, dysuria, hesitancy, or urinary frequency. For the past 3 days, the patient has had rhinorrhea, nasal congestion, and a sore throat, but these symptoms are improving. He has bilateral, sensorineural hearing loss that has worsened over the past 4 years. A maternal uncle died from complications of a renal transplant 5 years ago. Temperature is 37.1 C (98.8 F), blood pressure is 132/94 mm Hg, pulse is 90/min, and respirations are 14/min. The abdomen is soft and nontender and has no palpable masses. There is no suprapubic or costovertebral angle tenderness. Urinalysis reveals hematuria. Serum creatinine is 1.4 mg/dL, and serum complement levels are normal. A renal biopsy is performed. Which of the following is the most likely histologic finding?

Question

A 9-year-old boy is brought to the clinic for evaluation of dark brown urine for a day.  He has had no fever, dysuria, hesitancy, or urinary frequency.  For the past 3 days, the patient has had rhinorrhea, nasal congestion, and a sore throat, but these symptoms are improving.  He has bilateral, sensorineural hearing loss that has worsened over the past 4 years.  A maternal uncle died from complications of a renal transplant 5 years ago.  Temperature is 37.1 C (98.8 F), blood pressure is 132/94 mm Hg, pulse is 90/min, and respirations are 14/min.  The abdomen is soft and nontender and has no palpable masses.  There is no suprapubic or costovertebral angle tenderness.  Urinalysis reveals hematuria.  Serum creatinine is 1.4 mg/dL, and serum complement levels are normal.  A renal biopsy is performed.  Which of the following is the most likely histologic finding?

Quizplus · Accepted Answer

11ec25c8_d727_a87f_bc81_8959e4a44604_MD0003_00 Alport syndrome is an inherited, progressive disease affecting type IV collagen in the glomerular basement membrane (GBM), cochlea, and eye. The typical patient is a boy age <10 with gross hematuria after a recent upper respiratory infection, as in this case. Asymptomatic, microscopic hematuria often precedes gross hematuria, which recurs periodically and may be accompanied by hypertension, proteinuria, and chronic renal failure. Mutated collagen in the cochlea and eye results in sensorineural hearing loss and anterior lenticonus (conical lens protrusion), respectively. Most cases are X-linked, and patients often have a family history of chronic kidney disease, such as the renal transplant in this patient's uncle. History may also reveal hereditary hearing loss. Laboratory results may demonstrate elevated serum creatinine and normal complement levels. Diagnosis is confirmed by renal biopsy, with electron microscopy showing a lamellated GBM due to longitudinal splitting of the lamina densa. Genetic testing can also screen patients with a family history of Alport syndrome or confirm the diagnosis in a symptomatic patient. Management is supportive and may include transplant in patients with end-stage renal disease. (Choice A) Renal biopsy in minimal change disease shows effacement of podocyte foot processes. Patients are classically age <6 with marked proteinuria but no hematuria, renal insufficiency, or hypertension, making this diagnosis unlikely. (Choice B) Goodpasture syndrome is a progressive glomerulonephritis accompanied by pulmonary disease (ie, alveolar hemorrhage); biopsy reveals linear IgG deposition in the GBM. This patient has no pulmonary symptoms, and sensorineural hearing loss is not associated with Goodpasture syndrome. (Choice D) Biopsy in poststreptococcal glomerulonephritis reveals mesangial and glomerular capillary deposition of C3 and IgG. Patients typically have edema, hematuria, and hypertension. However, symptoms usually develop 1-3 weeks after streptococcal pharyngitis or impetigo, and the C3 level is decreased (not seen in this patient). (Choice E) IgA nephropathy is characterized by mesangial IgA deposition. Patients have concomitant gross hematuria and upper respiratory symptoms (eg, rhinorrhea, sore throat). Hypertension and renal insufficiency are rarely seen, and IgA nephropathy is not associated with sensorineural hearing loss. Educational objective: Alport syndrome is a progressive disease that presents with recurrent hematuria in boys age <10, often with a family history of renal failure and/or hearing loss. Complement levels are normal, and renal biopsy shows longitudinal splitting of the glomerular basement membrane. References: Alport syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/29262041) Alport syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/20301386)

A 9-Year-Old Boy Is Brought to the Clinic for Evaluation