Symptomatic Hemoglobin New Mexico and a Case of Therapeutic Benefit with Acetazolamide

Autor: Sara Nofal, Yuval Raizen, Crystal Jobson, Ahmed Ayad, Mona Lisa Alattar
Rok vydání: 2018
Předmět:
Zdroj: Blood. 132:4918-4918
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood-2018-99-119250
Popis: INTRODUCTION Inherited disorders due to rare structural Hb variants are not included in national, neonatal screening tests and therefore likely underdiagnosed. Hemoglobin New Mexico is one such rare variant with only one case ever reported in 1985 in conjunction heterozygosity for Hb S.1 This Hb variant involves a missense mutation of the β chain substituting the hydrophobic Proline β100 with the hydrophilic Arginine.1 We present here the second case of Hb New Mexico variant ever reported to our knowledge. CASE PRESENTATION An 18-year-old athletic, Latin American female initially presented with episodic chest pain, palpitations, fatigue, headaches, and dyspnea on exertion to the point that she could no longer exercise for one year. Work up revealed erythrocytosis persistent for >1 year with hemoglobin level of 17.3 g/dL, and hematocrit of 47.2 % (Hb went as high as 19g/dL) with normal erythropoietin level, hemoglobin electrophoresis, and JAK2 V617 with reflex to JAK3 exon 12-15 negative. She had extensive evaluation to rule out acquired causes including cardiac, pulmonary, and neurologic evaluation which was all normal. She underwent therapeutic phlebotomies with no clinical improvement over 3 months and symptoms worsened as well as new iron deficiency from phlebotomies so this was discontinued. Evaluation with p50 oxygen dissociation curve revealed high oxygen affinity. Further gene sequencing revealed heterozygous inheritance of Hb New Mexico with HbA: 54.5%, HbA2: 3.6%, and Hb New Mexico: 41.9%. Beta Globin Gene sequencing identified the following mutation: Beta 100, CCT>CGT, Pro>Arg. Her symptoms worsened as well as an episode of syncope but no new neurologic, cardiac, or pulmonary etiologies were identified and at the time Hg 18g/dL. A trial of low dose acetazolamide 125mg daily was given to the patient and her symptoms improved by a 6 week follow up with notable reduction of headache, fatigue, dyspnea, and chest pain. CONCLUSIONS Given the rarity of this hemoglobin variant in a patient with severe symptoms, data is limited. Acetazolamide, a carbonic anhydrase inhibitor often used for migraines, is known to illicit mild acidosis and therefore potentially reduce hemoglobin-oxygen affinity and perhaps allow for relief of our patient's symptoms. Further therapeutic evaluation is warranted but likely challenging given rarity of the condition. Disclosures No relevant conflicts of interest to declare.
Databáze: OpenAIRE
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