WBR0640

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology, MainCategory::Pathophysiology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 3-year-old boy is brought to the pediatrics clinic by his mother after she noticed that his urine had turned dark red. She reports that this is the first time she notices any change in urine color, and explains that her son has been healthy otherwise. Upon further questioning, the mother notes that her boy has been having speech difficulties and does not seem to be catching up to other kids his age. She also reports a history of kidney disease and hearing impairment in one of his uncles. You order a urinalysis that shows heavy red blood cells with dysmorphic morphology noted on cytology. Which of the following structures is likely defective in this patient? ]]
Answer A	AnswerA::A
Answer A Explanation	AnswerAExp::This refers to the glomerular capillary or endothelial cell. Endothelial involvement is not seen in Alport's syndrome. It may be seen in lupus nephritis or membranoproliferative glomerulonephritis.
Answer B	AnswerB::B
Answer B Explanation	AnswerBExp::Mesangial involvement is seen in IgA nephropathy usually not in Alport's Syndrome.
Answer C	AnswerC::C
Answer C Explanation	AnswerCExp::This refers to the glomerular podocyte. It is usually affected in focal segmental glomerulosclerosis.
Answer D	AnswerD::D
Answer D Explanation	AnswerDExp::This refers to the glomerular basement membrane which is usually defective in Alport's syndrome due to a mutation affecting the type 4 collagen.
Answer E	AnswerE::E
Answer E Explanation	AnswerEExp::This refers to the podocyte foot processes which are usually effaced in minimal change disease.
Right Answer	RightAnswer::D
Explanation	[[Explanation:: Alport’s syndrome (hereditary nephritis) is a familial nephropathy characterized by renal impairment, auditory manifestations, and occasionally ocular defects. It has an X-linked form 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. 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. Alport’s syndrome most commonly presents in childhood with persistent hematuria; a presentation that should always consider a range of more common differential diagnoses before the diagnosis of Alport’s syndrome is made. The prognosis of Alport’s syndrome is generally poor with inevitable progression to end-stage renal disease (ESRD) at varying rates. Management is with a multidisciplinary approach, involving pharmacologic therapy to slow the progression of renal dysfunction as well as visual and hearing aids for those with significant oculo-auditory impairment. Educational Objective: Alport's syndrome is a form of hereditary nephritis that presents with hematuria and hearing impairment due to defective collagen type IV the main component of the glomerular basement membrane. References: Kruegel J, Rubel D, Gross O. Alport syndrome-insights from basic and clinical research. Nat Rev Nephrol. 2013;9(3):170-8.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Alport's syndrome, WBRKeyword::Collagen type 4, WBRKeyword::Basement membrane, WBRKeyword::Hearing loss, WBRKeyword::Hematuria, WBRKeyword::Nephritis Syndrome, WBRKeyword::Glomerulonephritis
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