WBR0290

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1], Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry, MainCategory::Pathology
Sub Category	SubCategory::Gastrointestinal, SubCategory::Neurology
Prompt	[[Prompt::A 10-year-old girl is brought to the emergency department for complaints of fever, recurrent watery diarrhea, and abdominal pain. Her family emigrated from Romania 1 year ago, and the child has not received any medical care since. The mother reports that her child has had a history of recurrent sinusitis and multiple hospitalizations for pneumonia since the age of 4. On physical examination, you notice a sick looking girl with a fair complexion, sparse light blonde hair, and blue eyes. You also note mild hepatosplenomegaly, diffuse petechiae, and decreased pin-prick sensation in both lower extremities. Which of the following defects is most likely to be responsible for this patient's condition?]]
Answer A	AnswerA::Dynein arm defect
Answer A Explanation	AnswerAExp::Primary ciliary dyskinesia or Kartagener syndrome is caused by a dynein arm defect leading to a lack in effective ciliary motility. Dynein arm defects are not associated with Chediac-Higashi syndrome.
Answer B	AnswerB::Lysosomal degranulation defect
Answer B Explanation	AnswerBExp::A lysosomal degranulation defect with failure of phagolysosome formation is the main mechanism of disease in Chediac-Higashi syndrome.
Answer C	AnswerC::Type 1 collagen defect
Answer C Explanation	AnswerCExp::Type 1 collagen defects are responsible for osteogenesis imperfecta.
Answer D	AnswerD::Nucleotide excision repair defect
Answer D Explanation	AnswerDExp::Nucleotide excision repair defects are responsible for Xeroderma pigmentosum.
Answer E	AnswerE::Fibrillin protein defect
Answer E Explanation	AnswerEExp::Fibrillin protein defects cause Marfan syndrome and Weill-Marchesani syndrome. Chediak-Higashi syndrome is not associated with fibrillin protein defects.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive immunodeficiency disorder characterized by bleeding tendency, recurrent pyogenic bacterial infections, partial albinism, and progressive neurologic dysfunction. The classical pathologic feature of CHS is enlarged lysosomes or lysosome-related organelles in all cell types. These abnormal and dysfunctional lysosomes form as a result of abberant degranulation and fusion the phagosome and the maturing lysosome. The disorder is caused by a mutation in the CHS1/LYST gene. The disease is extrememly rare with around 500 cases reported worldwide. The most documented presentation, and indication for work-up, is recurrent pyogenic infections in a patient with partial albinism. The disorder may also present with an ‘accelerated phase’, a lymphoproliferative disorder characterized a lymphocytic infiltration of the major organs of the body. Patients with CHS are treated with prophylactic antibiotics as soon as the diagnosis is made. The only successful treatment for CHS is allogenic bone marrow transplantation. To remember the characteristic presentation of CHS, remember the 4 P's: Partial albinism, Pyogenic infections, Platelet dysfunction, and Peripheral neuropathy. Educational Objective: Chediak-Higashi syndrome is a rare, autosomal recessive immunodeficiency disorder caused by a defect in lysosomal degranulation and phagolysosome formation. It presents with partial albinism, peripheral neuropathy, bleeding tendency, and pyogenic sinopulmonary infections. Other findings include lymphadenopathy, hepatosplenomegaly, and mucosal ulcerations. References: Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. Jan 2008;15(1):22-9.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Sinopulmonary infections, WBRKeyword::Peripheral neuropathy, WBRKeyword::Partial albinism, WBRKeyword::Pyogenic infections, WBRKeyword::Chediak-Higashi syndrome, WBRKeyword::Phagolysosome, WBRKeyword::Lysosomal degranulation, WBRKeyword::Congenital immunodeficiency, WBRKeyword::Immunodeficiency syndromes
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