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 region. 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 stones. Following further investigation, the physician explains to the patient that the patient's condition is caused by a genetic disorder characterized by a mutation in the amino acid transporters in the kidneys. Further genetic testing reveals the woman carries the same mutation but does not manifest it. 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. If the mother was 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 to develop the disease.]]
Answer D	AnswerD::75%
Answer D Explanation	AnswerDExp::Cystinuria is inherited in an autosomal recessive pattern. The couple's child has a 50% chance of developing cystinuria.
Answer E	AnswerE::100%
Answer E Explanation	[[AnswerEExp::An example of 100% chance of developing a genetic disease is the development of an X-linked dominant disorder among daughters who inherit a mutant X-allele from an affected father. All daughters have a 100% chance of developing the disease since they can only inherit the mutant X chromosome from their father.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::The features of the patient's pain (location, radiation, and severity) and findings on the physical examination (costovertebral angle tenderness), and urinalysis (hematuria and hexagonal stones) are all consistent with the diagnosis of kidney stones (nephrolithiasis). In addition, the patient's recurrent presentation is concerning and warrants an 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 are often suggested by the presence of hexagonal stones on urinalysis. Given the autosomal recessive pattern of inheritance, the patient must have 2 copies of the mutant allele. On the other hand, his wife is a carrier of the disease but does not manifest it, so she must have only one copy of the mutant allele. Accordingly, the couple's child will inherit one allele from the father (100% mutant) and another allele from the mother (50% mutant), and the percentage of developing cystinuria is thus 50%. 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. The offspring of an individual with the disease and an individual who carries the allele has a 50% chance to develop the disease. 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::