WBR0279

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A 72-year-old man with a history of type 2 diabetes presents to the physician’s office for progressive loss of vision. He explains that recently, he has been sensing that all lights are too bright and has been seeing halos around lights. His night vision has become much worse in the past few months, and he has been avoiding driving at night. His temperature is 36.6 °C (97.88 °F), his blood pressure is 136/80 mmHg, and his heart rate is 76/min. Laboratory findings are remarkable for a blood glucose level of 320 mg/dL and HbA1c of 9.9 mmol/mol. The accumulation of which substance is associated with the development of this patient’s progressive vision loss?]]
Answer A	AnswerA::Fructose
Answer A Explanation	AnswerAExp::Fructose accumulation causes essential fructosuria, which would result in the deficiency of fructokinase. It is a benign condition, and patients are usually asymptomatic.
Answer B	AnswerB::Sorbitol
Answer B Explanation	[[AnswerBExp::The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients.]]
Answer C	AnswerC::Galactose
Answer C Explanation	AnswerCExp::Galactose accumulation results from galactokinase deficiency. Galactose appears in blood and urine and may cause infantile cataracts. It is a relatively mild condition.
Answer D	AnswerD::Galactitol
Answer D Explanation	[[AnswerDExp::Galactitol accumulation is due to the deficiency or the absence of the enzyme galactose-1-phosphate uridyltransferase, which causes galactosemia. Galactosemia is an autosomal recessive disorder associated with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and mental retardation.]]
Answer E	AnswerE::Glycogen
Answer E Explanation	AnswerEExp::Intracellular accumulation of glycogen results in abnormal glycogen metabolism and glycogen storage diseases.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Cataract is the progressive and cumulative loss of lens transparency (opacification) that results in vision loss in the affected eye. Cataract is the leading cause of blindness worldwide. It is considered an early complication of diabetes mellitus. The incidence of cataract increases by 2 to 5 times among diabetic patients, and the incidence further increases significantly among diabetics who are diagnosed with diabetes before the age of 40. Patients often complain of light scatter, subjective glare with halos around lights, and vision loss that may affect daily activities such as reading or driving. The pathophysiology of cataracts involves 3 molecular mechanisms: First, non-enzymatic glycation of lens proteins; second, oxidative stress; and third, activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and consequent accumulation of intracellular sorbitol. Excess sorbitol within the fibrils of the lens results in movement of water into the lens fibrils and leads to swelling of the lens fibrils and cataract formation. Educational Objective: The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients. References: Javadi M, Zarei-Ghanavati S. Cataracts in diabetic patients: a review article. J Ophthalmic Vis Res. 2008;3(1):52-65. Malone JI, Lowitt S, Cook WR. Nonosmotic diabetic cataracts. Pediatr Res. 1990;27(3):293-6. Lightman S. Does aldose reductase have a role in the development of the ocular complications of diabetes? Eye. 1993;7:238-241. First Aid 2014 page 107, 327]]
Approved	Approved::Yes
Keyword	WBRKeyword::Diabetes mellitus, WBRKeyword::Diabetes, WBRKeyword::Cataract, WBRKeyword::Cataracts, WBRKeyword::Sorbitol, WBRKeyword::Accumulation, WBRKeyword::Aldose reductase, WBRKeyword::Osmotic damage
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