WBR0981

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry, MainCategory::Genetics
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 27-year-old man presents to the emergency department with severe left flank pain for the past 3 hours. He states the pain is a sharp, stabbing sensation that radiates to his left groin. Upon further questioning, the patient recalls that he has had similar episodes in the past. Physical examination is remarkable for left costovertebral angle tenderness. Urinalysis demonstrates hematuria and hexagonal-shaped crystals. Following further investigation, the physician explains to the patient that his condition is caused by a genetic disorder characterized by a mutation in an amino acid transporters in the kidneys. If genetic testing reveals the patient's wife does not carry a similar mutation, what is the percentage that this couple's child will have the disease?]]
Answer A	AnswerA::0%
Answer A Explanation	[[AnswerAExp::Cystinuria is an autosomal recessive disease. As the mother is not a carrier of the mutant allele (has 2 wild-type alleles), the couple's child would have had 0% chance of developing cystinuria and 100% chance of carrying a mutant allele.]]
Answer B	AnswerB::25%
Answer B Explanation	AnswerBExp::Had both the child's father and mother been carriers of the mutant allele, they would not have manifested the disease themselves, and their child would have had a 25% chance of developing cystinuria.
Answer C	AnswerC::50%
Answer C Explanation	[[AnswerCExp::Cystinuria is inherited in an autosomal recessive pattern. Patients who manifest the disease have 2 mutant alleles, while carriers of the mutation have only 1 mutant allele. The offspring of an individual with the disease and an individual who carries the allele has a 50% chance of developing the disease.]]
Answer D	AnswerD::75%
Answer D Explanation	AnswerDExp::Cystinuria is inherited in an autosomal recessive pattern. The couple's child has a 0% chance of developing cystinuria.
Answer E	AnswerE::100%
Answer E Explanation	AnswerEExp::An example of a 100% chance of a child developing cystinuria is when both parents have fully manifest disease (both carry 2 mutant alleles). In that case all offspring would have the disease too.
Right Answer	RightAnswer::A
Explanation	[[Explanation::The features of the patient's pain (location, radiation, and severity) and findings on physical examination (costovertebral angle tenderness), and urinalysis (hematuria and hexagonal-shaped crystals) are all consistent with the diagnosis of kidney stones (nephrolithiasis). In addition, the patient's recurrent presentation is concerning and warrants further investigation for an underlying etiology of his condition. Cystinuria is an autosomal recessive genetic disease characterized by reduced renal reabsorption of positively charged amino acids. It is caused by the presence of abnormal transporters in the kidneys for cysteine, ornithine, lysine, and arginine. Cystinuria results in impaired renal reabsorption and excessive excretion of these amino acids, and patients with cystinuria are predisposed to the development of recurrent cystine stones, which often manifest with hexagonal-shaped crystals on urinalysis. Given the autosomal recessive pattern of inheritance, the patient must have 2 copies of the mutant allele. Given that the mother is not a carrier of the mutant allele, There is a 100% chance that a child may be a silent carrier of the mutation, but a 0% chance that the disease will manifest phenotypically. Educational Objective: Cystinuria is inherited in an autosomal recessive pattern. Patients who manifest the disease have 2 mutant alleles, while carriers of the mutation have only 1 mutant allele. References: First Aid 2014 page 111]]
Approved	Approved::Yes
Keyword	WBRKeyword::Cystinuria, WBRKeyword::Cysteine, WBRKeyword::Cystine stone, WBRKeyword::Kidney stone, WBRKeyword::Nephrolithiasis, WBRKeyword::Autosomal recessive, WBRKeyword::Allele, WBRKeyword::Mutant, WBRKeyword::Hematuria, WBRKeyword::Flank pain
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::