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. Enzyme assays monitor the accumulation of products of the galactose metabolic pathway following the addition of radiolabeled substrates. 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 o 14C galactose-1-phosphate after the addition of 14 C galactose is observed in galactokinase deficiency]]. The patient’s condition is inconsistent with the diagnosis of galactokinase deficiency because this condition is mild and is associated with the occurrence of cataratcs but not mental retardation, failure to thrive and severe symptoms of jaundice and vomiting.]]
Answer C	[[AnswerC::Accumulation of UDP 14C 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 will more likely reveal an absence , not accumulation, of any detectable UDP 14C galactose after the addition of 14C galactose 1 phosphate.]]
Answer D	[[AnswerD::Accumulation of 14C galactose 1 phosphate after the addition of 14C galactose]]
Answer D Explanation	[[AnswerDExp::Classic galactosemia is characterized by the absence of galactose 1 phosphate uridyltransferase (GALT). Accumulation of 14C galactose 1 phosphate after the addition of 14C galactose is not characteristic of the absence of this enzyme.]]
Answer E	[[AnswerE::Absence of any detectable UDP 14C glucose 1 phosphate after the addition of 14C UDP glucose]]
Answer E Explanation	[[AnswerEExp::Absence of any detectable UDP 14C glucose 1 phosphate after the addition of 14C UDP glucose can be present in the absence of the enzyme UDP glucose pyrophosphate and not in the absence of galactose 1 phosphate uridyltransferase (GALT).]]
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 gaalctose 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
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::