WBR0191

Author	[[PageAuthor::Mahmoud Sakr M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 14-year-old girl is brought to the physician's office with complaints of frequent falls, stumbling gait, and slurred speech. Her mother explains that the patient's symptoms have been progressing for the past few years. On physical examination, the patient has moderate scoliosis and pes cavus. Neurological examination is remarkable for dysarthria, staggering gait , weakness of the distal lower extremities, loss of vibratory and proprioceptive sensation, absent deep tendon reflexes, and positive Babinski sign. Heart auscultation reveals an S4 gallop. Which of the following endocrine abnormalities is associated with this patient's condition?]]
Answer A	AnswerA::Adrenal insufficiency
Answer A Explanation	AnswerAExp::Friedreich's ataxia is classically associated with adrenal insufficiency.
Answer B	AnswerB::Diabetes mellitus
Answer B Explanation	AnswerBExp::Approximately 20% of patients with Friedreich's ataxia develop carbohydrate intolerance and 10% develop diabetes mellitus.
Answer C	AnswerC::Cushing syndrome
Answer C Explanation	AnswerCExp::Friedreich's ataxia is not classically associated with Cushing syndrome.
Answer D	AnswerD::Polycystic ovaries
Answer D Explanation	AnswerDExp::Friedreich's ataxia is not classically with polycystic ovaries.
Answer E	AnswerE::Acromegaly
Answer E Explanation	AnswerEExp::Friedreich's ataxia is not classically associated with acromegaly.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease characterized by a transcription defect caused by GAA trinucleotide repeats in the Frataxin gene on the long arm of chromosome 9. The defect of the Frataxin gene results in a deficient frataxin protein, an iron-binding protein, in the mitochondria and a reduction of overall mitochondrial metabolism. The hallmark of FRDA is a CNS and PNS disease with involvement of the heart, skeleton, and endocrine system. FRDA affects children aged 9-16 years old, and patients usually die before they reach 40 years of age. Neurological manifestations of FRDA include dysarthria, staggering gait ("clumsy" children) and dysmetria of the extremities due to involvement of the spinocereballar tissue, weakness of the lower extremities due to involvement of the corticospinal tracts, loss of vibratory and priopioceptive sensation due to involvement of the dorsal columns, areflexia, stocking-and-glove type sensory neuropathy, and positive Babinski sign. Other clinical features include hypertrophic cardiomyopathy, which may be the first manifestation of the disease and is often the cause of death. Hypertrophic cardiomyopathy may be suggested on physical examination by the presence of an S4 gallop, a low-pitched sound present late in diastole that immediately precedes S1. Skeletal abnormalities usually include scoliosis, kyphoscoliosis, and pes cavus of the feet. Approximately 20% of individuals with FRDA develop carbohydrate intolerance, and 10% develop diabetes mellitus. Diabetes mellitus is usually a late manifestation of the disease and may be due to either insulin-dependence or glucose intolerance without insulin dependence. Although the association is clear, the exact pathogenesis for the association of diabetes mellitus and FRDA is poorly understood. Educational Objective: Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease characterized by a transcription defect caused by GAA trinucleotide repeats in the Frataxin gene on the long arm of chromosome 9. The hallmark of FRDA is a CNS disease with involvement of the heart, skeleton, and endocrine system. Diabetes mellitus is usually a late manifestation of FRDA References: Schoenle EJ, Boltshauser EJ, Baekkeskov S, et al. Preclinical and manifest diabetes mellitus in young patients with Friedreich's ataxia. no evidence of immune process behind the islet cell destruction. Diabetologia. 1989;32:378-81. Gonzalez-Cabo P, Palau F. Mitochondrial pathophysiology in Friedreich's ataxia. J Neurochem. 2013; 126 Suppl 1:53-64. Koeppen AH. Friedreich's ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011; 303(1):1-12. First Aid 2014 page 468]]
Approved	Approved::Yes
Keyword	WBRKeyword::Friedreich ataxia, WBRKeyword::FRDA, WBRKeyword::Diabetes mellitus, WBRKeyword::Pes cavus, WBRKeyword::Hypertrophic cardiomyopathy, WBRKeyword::CNS, WBRKeyword::PNS, WBRKeyword::Spinal cord, WBRKeyword::Ataxia, WBRKeyword::GAA, WBRKeyword::Neurodegenerative disease, WBRKeyword::Autosomal recessive
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