WBR0293

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A 4-month old boy is brought to the physician's office for psychomotor delay. The mother explains that the patient cannot sit or support his head. She states that his symptoms began when she noticed orange crystals in his diapers 5 weeks ago and have been progressively worsening. The boy has no significant past medical history and had a normal neonatal course. Laboratory findings demonstrate megaloblastic anemia, normal concentrations of vitamin B12 and folate, and increased concentrations of uric acid in blood and in urine. What type of inheritance pattern is associated with this patient's condition?]]
Answer A	AnswerA::X-linked recessive disorder
Answer A Explanation	[[AnswerAExp::Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by the deficiency of hypoxanthine-ribosyl-phosphoribosyltransferase (HGPRT) enzyme.]]
Answer B	AnswerB::X-linked dominant disorder
Answer B Explanation	AnswerBExp::Hypophosphatemic rickets is an example of an X-linked dominant disorder.
Answer C	AnswerC::Autosomal dominant disorder
Answer C Explanation	AnswerCExp::Huntington's disease, hereditary hemorrhagic telangiectasia, Marfan syndrome, neurofibromatosis types 1 and 2, tuberous sclerosis, and von-Hippel Lindau are all examples of autosomal dominant disorders.
Answer D	AnswerD::Autosomal recessive disorder
Answer D Explanation	AnswerDExp::Albinism, cystic fibrosis, Kartagener syndrome, sickle cell disease, and phenylketonuria are all examples of autosomal recessive disorders.
Answer E	AnswerE::Mitochondrial inheritance
Answer E Explanation	AnswerEExp::MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibers) and MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) are 2 examples of diseases with mitochondrial inheritance.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by the deficiency of hypoxanthine-ribosyl-phosphoribosyltransferase (HGPRT) that normally converts hypoxanthine to inosine monophosphate (IMP), guanine to guanosine monophasphate (GMP), and xanthine to xanthosine monophosphate. As a result, the purine salvage pathway is defective and the patient has to undergo de novo purine synthesis. Lesch-Nyhan syndrome often first manifests with formation of orange crystals in the diapers or with urinary tract obstruction caused by heavy crystalluria. Lab findings consistent with Lesch-Nyhan syndrome include megaloblastic anemia (often with normal concentrations of vitamin B12 and folate) and hyperuricemia, where excessive uric acid production results from the increase de novo production of purines. Although patients usually have a normal neonatal course, psychomotor delay often develops between 3-6 months with hypothonic and choreoathetosis. In contrast, self-mutilation and aggressive behavior (lip biting and finger chewing) are more evident when patients develop teeth. Educational Objective: Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by the deficiency of hypoxanthine-ribosyl-phosphoribosyltransferase (HGPRT) enzyme. References: Nyhan WL. The Lesch-Nyhan syndrome. Annu Rev Med. 1973;24:41-60. Ernst M, Zametkin AJ, Matochik JA, et al. Presynaptic dopaminergic deficits in Lesch-Nyhan disease. N Engl J Med. 1996;334(24):1568-72. van der Zee SP, Schretlen ED, Monnens LA. Megaloblastic anaemia in the Lesch-Nyhan syndrome. Lancet. 1968;1(7557):1427. First Aid 2014 page 68, 88]]
Approved	Approved::Yes
Keyword	WBRKeyword::HGPRT, WBRKeyword::Lesch-Nyhan syndrome, WBRKeyword::Psychomotor delay, WBRKeyword::Orange crystals, WBRKeyword::Self-mutilation, WBRKeyword::Aggressive behavior, WBRKeyword::Hyperuricemia, WBRKeyword::Gout, WBRKeyword::Megaloblastic anemia, WBRKeyword::Hypoxanthine-guanine phosphoribosyltransferase, WBRKeyword::Purine salvage, WBRKeyword::X-linked recessive disorder
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