WBR0908

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::Elevated levels of galactose are detected in a newborn screening test and prompt further investigation for a galactose metabolism disorder. An erythrocyte enzyme assay that monitors the accumulation of products of the galactose metabolic pathway following the addition of a radiolabeled substrate is carried out. The enzyme assay confirms the diagnosis of a galactose metabolism disorder that leads to mental retardation, failure to thrive, and jaundice if galactose is not eliminated from the diet. Which of the following is most likely the result of the enzyme assay in this patient?]]
Answer A	[[AnswerA::Absence of 14C UDP-galactose after the addition of 14C galactose-1-phosphate]]
Answer A Explanation	[[AnswerAExp::Classic galactosemia is characterized by the absence of galactose-1-phosphate uridyltransferase (GALT) resulting in the absence of detectable UDP 14C galactose after the addition of 14C galactose-1-phosphate as a substrate.]]
Answer B	[[AnswerB::Absence of 14C galactose-1-phosphate after the addition of 14C galactose]]
Answer B Explanation	[[AnswerBExp::Absence of 14C galactose-1-phosphate after the addition of 14 C galactose is observed in galactokinase deficiency. Galactokinase deficiency is a relatively mild disorder associated with early-onset cataracts with no effect on early development.]]
Answer C	[[AnswerC::Accumulation of 14C UDP-galactose after the addition of 14C galactose-1-phosphate]]
Answer C Explanation	[[AnswerCExp::Classic galactosemia characterized by the absence of galactose-1-phosphate uridyltransferase (GALT). The enzyme assay would reveal an absence , not accumulation, of 14C UDP-galactose after the addition of 14C galactose-1-phosphate.]]
Answer D	[[AnswerD::Accumulation of 14C UDP-galactose after the addition of 14C galactose]]
Answer D Explanation	[[AnswerDExp::Accumulation of 14C UDP-galactose after the addition of 14C galactose occurs in the absence of the UDP-glucose 4-epimerase (GALE) enzyme.]]
Answer E	[[AnswerE::Absence of 14C glucose-1-phosphate or 14C galactose-1-phosphate after the addition of 14C lactose.]]
Answer E Explanation	AnswerEExp::This enzyme assay finding is observed in patients with lactase deficiency, i.e. lactose intolerance.
Right Answer	RightAnswer::A
Explanation	[[Explanation::This patient most likely suffers from classic galactosemia, a autosomal recessive disorder of galactose metabolism characterized by the absence of galactose-1-phosphate uridyltransferase (GALT) resulting in the accumulation of galactose-1-phosphate, galactose and galacticol. Classic galactosemia leads to severe manifestations early on in life if galactose is not eliminated from the diet. Patients present with failure to thrive and mental retardation. The radiolabeled enzyme assay will most likely demonstrate complete absence of 14C UDP-galactose after the addition of 14C galactose-1-phosphate. Infants in the United States are routinely screened for galactosemia as part of their newborn screening. Prenatal testing with chorionic villus sampling or amniocentesis is also possible. Despite early diagnosis and diet restriction a significant portion of patients have serious complications including neurological deficits and learning disabilities. Educational Objective: Classic galactosemia is characterized by the absence of galactose-1-phosphate uridyltransferase (GALT) which is the enzyme needed to convert galactose-1-phosphate to UDP-galactose. References: Cuthbert C. Diagnosis of inherited disorders of galactose metabolism. Curr Protoc Hum Genet. 2008 Jan;Chapter 17:Unit 17.5.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Galactose, WBRKeyword::Classic galactosemia, WBRKeyword::Galactosemia, WBRKeyword::Galactokinase deficiency, WBRKeyword::Lactose, WBRKeyword::Lactase deficiency, WBRKeyword::Lactose intolerance, WBRKeyword::Enzyme, WBRKeyword::Enzyme assay
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::