WBR0219

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics, MainCategory::Pathophysiology
Sub Category	SubCategory::Head and Neck, SubCategory::Renal
Prompt	[[Prompt::A 7-year-old boy is brought to his pediatrician's office for progressive bilateral deafness. Family history is significant for a similar condition among multiple family members. Physical examination is remarkable for subcapsular posterior lens opacities, peripheral coalescing retinopathy, and high-tone sensorineural deafness. The physician suspects the patient's condition is caused by a genetic disease. Genetic testing results demonstrate a mutation in the COL4A5 gene. Which test is most likely to reveal abnormal findings during further work-up of this patient?]]
Answer A	AnswerA::Serum creatinine
Answer A Explanation	[[AnswerAExp::Alport's syndrome is a familial cause of deafness, ocular disturbances, and nephritis. Although patients usually develop end stage renal disease (ESRD), serum creatinine is often normal early in the course of the disease or among patients with mild disease.]]
Answer B	AnswerB::Electrocardiogram
Answer B Explanation	AnswerBExp::Alport's syndrome is not primarily associated with cardiac disease or changes on electrocardiogram (ECG).
Answer C	AnswerC::Urinalysis
Answer C Explanation	[[AnswerCExp::Alport's syndrome is a familial cause of deafness, ocular disturbances, and nephritis. Microscopic hematuria is the most common presenting sign of patients with Alport's syndrome. Hematuria is usually present before patients experience symptoms of renal failure (eg. hypertension) and before an elevation in serum creatinine is observed.]]
Answer D	AnswerD::Serum alanine aminotransferase
Answer D Explanation	AnswerDExp::Alport syndrome is not primarily associated with abnormal values of alanine aminotransferase (ALT) or liver abnormalities.
Answer E	AnswerE::Serum platelet count
Answer E Explanation	AnswerEExp::Alport's syndrome is not primarily associated with quantitative platelet disturbances.
Right Answer	RightAnswer::C
Explanation	[[Explanation:: Alport’s syndrome (hereditary nephritis) is a familial nephropathy characterized by renal impairment, auditory manifestations, and ocular defects. It has an X-linked form, which is characterized by the mutation of COL4A5 gene on the long arm of the X-chromosome, and another much less common autosomal recessive form characterized by the homogeneous mutation of COL4A3 or COL4A4 on chromosome 2. Notably, the 2 forms may also be distinguished by identification of a patient's pedigree. The mutation leads to abnormal alpha chain of type IV collagen, which is normally responsible for the structure and function of basement membranes in the body. Histopathological analysis of the kidneys demonstrates a lamellated glomerular basement membrane (GBM) with the appearance of false layers, along with glomerular focal sclerosis. Renal molecular analysis reveals absence of collagen network of the GBM. Alport’s syndrome commonly presents in childhood with persistent hematuria. Prognosis of Alport’s syndrome is generally poor with inevitable progression to end-stage renal disease (ESRD) at varying rates. Alport's syndrome should always be considered among children with any of auditory, ocular, and/or urinary findings. Nonetheless, it should be distinguished from other diseases that may present with similar symptoms (table below). Microscopic hematuria is the most common presenting sign of patients with Alport's syndrome. Hematuria is usually present before patients experience symptoms of renal failure (eg. hypertension) and before either proteinuria or an elevation in serum creatinine is observed. Management of renal disease in Alport's syndrome is usually by ACE-inhibitors that may delay disease progression to ESRD. ESRD requires renal replacement modalities, such as dialysis and renal transplantation. Genetic counseling is recommended for families and patients with Alport's syndrome. Educational Objective: Alport's syndrome is a familial cause of deafness, ocular disturbances, and nephritis. Microscopic hematuria is the most common presenting sign of patients with Alport's syndrome. References: McCarthy PA, Maino DM. Clin Eye Vis Care. 2000; 12(3-4):139-50. Savige J, Gregory M, Gross O, et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol. 2013; 24(3):364-75. First Aid 2014 page 538]]
Approved	Approved::Yes
Keyword	WBRKeyword::Alport's syndrome, WBRKeyword::Alport, WBRKeyword::Nephritis, WBRKeyword::Deafness, WBRKeyword::Hearing loss, WBRKeyword::Hematuria, WBRKeyword::Creatinine, WBRKeyword::Work-up, WBRKeyword::COL4A5, WBRKeyword::Hereditary nephritis
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