WBR0243

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Neurology, SubCategory::General Principles
Prompt	[[Prompt::An 8-year-old boy is brought to the emergency department with generalized epilepsy. His mother reports that the boy's past medical history is only significant for myoclonus and resting muscle pain at the age of 6 years. His family history is significant for a similar condition in his maternal aunt, whose symptoms then progressed to generalized epilepsy, weakness, ataxia, dementia, and early death. On physical examination, the patient appears very short compared to his peers. The physician also notes optic atrophy and hearing loss. ECG reveals pre-excitation delta waves. Which additional finding will most likely be present during further work-up of this patient?]]
Answer A	AnswerA::Hyperbilirubinemia
Answer A Explanation	AnswerAExp::MERRF is associated with elevated lactic acid that is not due to hemolysis. Hyperbilirubinemia is not usually associated with MERRF.
Answer B	AnswerB::Ketoacidosis
Answer B Explanation	AnswerBExp::MERRF is associated with elevated lactate in blood and CSF, not ketones. Thus, lactic acidosis is commonly observed in patients with MERRF, not ketoacidosis. Patients with untreated type 1 diabetes mellitus usually present with ketoacidosis.
Answer C	AnswerC::Respiratory acidosis
Answer C Explanation	AnswerCExp::MERRF is not classically associated with respiratory acidosis.
Answer D	AnswerD::Lactic acidosis
Answer D Explanation	AnswerDExp::MERRF is associated with elevated lactate and pyruvate in the blood and in CSF. MERRF is associated with lactic acidosis.
Answer E	AnswerE::Undetectable proteins in CSF
Answer E Explanation	AnswerEExp::Elevated proteins in CSF are often observed in patients with MERRF
Right Answer	RightAnswer::D
Explanation	[[Explanation::Myoclonic epilepsy with ragged red fibers (MERRF) is a multisystem disease that is caused by mutations in the mitochondrial DNA (mtDNA). Most commonly, the disease is caused by a mutation of the MT-TK gene of the mtDNA that encodes tRNA lysine. Manifestations of the disease are myoclonus, resting muscle pain, and short stature (early symptoms) followed by generalized epilepsy, hearing loss, and exercise intolerance. Some patients might develop cardiomyopathy with Wolff-Parkinson-White (WPW) syndrome (pre-excitation delta waves on ECG), retinopathy, pyramidal signs, parkinsonism, or multiple lipomas. Patients are usually normal at birth, but symptoms progressively appear during childhood with gradual worsening. Symptoms of advanced disease include ataxia, weakness, and dementia. The diagnosis is made by detection of ragged red fibers on muscle biopsy and presence of mtDNA mutation in leukocytes. Although the genetic mutation is present in all cells, heteroplasmy can lead to a variable distribution of mutated mtDNA across cells. Additional testing may be helpful for the diagnosis. CSF analysis may show elevated proteins in CSF and elevated lactate and pyruvate in blood and in CSF. ECG may show pre-excitation delta waves consistent with WPW syndrome, electroencephalogram (EEG) often demonstrates generalized spike and wave discharges, and brain MRI may show brain atrophy and calcification in the basal ganglia. Educational Objective: Myoclonic epilepsy with ragged red fibers (MERRF) is a multisystem disease that is caused by mutations in the mitochondrial DNA (mtDNA). Manifestations of the disease are myoclonus, generalized epilepsy, short stature, hearing loss, and lactic acidosis. References: DiMauro S, Hirano M. MERRF. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. First Aid 2014 page 86]]
Approved	Approved::Yes
Keyword	WBRKeyword::Heteroplasmy, WBRKeyword::Mitochonria, WBRKeyword::Mitochondrial disorder, WBRKeyword::MERRF, WBRKeyword::Myoclonus, WBRKeyword::Epilepsy, WBRKeyword::mtDNA, WBRKeyword::Ragged red fibers, WBRKeyword::Myoclonic epilepsy with ragged red fibers
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