Hb Grove City [ß38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G]: a new low oxygen affinity ß chain variant.

A previously unreported ß chain hemoglobin (Hb) variant, Hb Grove City [ß38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G], was discovered in a woman who presented with hypoxia and mild anemia. Her young daughter also tested positive for the variant and displayed similar symptoms. Hemoglobin-oxygen dissociation testing confirmed right-shifted oxygen dissociation curves. A corresponding Hb variant was detected by high performance liquid chromatography (HPLC) and intact mass spectrometry (MS) but was not detected by capillary electrophoresis (CE), isoelectrofocusing (IEF) or alkaline or acid electrophoresis. DNA sequencing analysis confirmed a ß-globin gene mutation. All three previous mutations at this locus affect oxygen affinity, as does this new variant. This newly described variant showed variable stability results and therefore may be mildly unstable but is not associated with microcytosis, significant hemolysis or clinically evident cyanosis. It is important to consider hemoglobinopathies in patients who are anemic and have unexplained hypoxia. Arterial blood gas and p50 evaluations may prevent unnecessary diagnostic interventions. Additionally, Hb variants with altered oxygen affinity can be electrophoretically silent; therefore, multiple methods including MS and/or DNA sequencing are warranted when clinical suspicion is high.

Knowledge of alpha-1 antitrypsin deficiency among internal medicine house officers and respiratory therapists: results of a survey.

BACKGROUND: Alpha-1 antitrypsin deficiency is a common genetic condition that predisposes to emphysema and liver disease. Alpha-1 antitrypsin deficiency is under-recognized, so affected individuals often experience long delays in diagnosis and visits to multiple physicians before correct diagnosis. Reasoning that inadequate knowledge about alpha-1 antitrypsin deficiency could contribute to this under-recognition, we designed this study to evaluate internal medicine house officers' and respiratory therapists' (RTs) knowledge of alpha-1 antitrypsin deficiency. METHODS: We evaluated knowledge of alpha-1 antitrypsin deficiency with a Web-based test containing 30 multiple-choice questions. Invitations to take the test were sent via e-mail to all internal medicine house officers and RTs at The Cleveland Clinic main campus hospital. We assessed test scores by profession, years of training/experience, and self-assessed knowledge of alpha-1 antitrypsin deficiency. RESULTS: Of 332 invitees, 202 (61%) responded, of whom 165 (50%) provided complete responses (99 RTs, 66 physicians). The mean scores (percent of correct answers) were 54% and 52% for physicians and RTs, respectively (P = .25). The scores did not differ among the physicians when examined by subspecialty (pulmonary/critical care vs other) or post-graduate education level (P = .94). RTs who had graduated from a 4-year respiratory therapy program had a higher mean score than those who had graduated from a 2-year program (56% vs 50%, P = .02). Respondents' whose self-assessment of their knowledge about alpha-1 antitrypsin deficiency was "somewhat knowledgeable" had higher test scores than any other self-assessed knowledge level, regardless of profession. CONCLUSIONS: These results indicate a generally low level of knowledge about alpha-1 antitrypsin deficiency among physicians and RTs. Causes of under-recognition of alpha-1 antitrypsin deficiency, including the possibility of poor knowledge as a contributor, warrant further study.