Detection of Hb Rothschild HBB: c.[112T>A or 112T>C], Through High Index of Suspicion on Abnormal Pulse Oximetry.

We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO2) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [ß37(C3)Trp→Arg] (HBB: c.[112 T>A or 112 T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1ß2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.

Bone marrow aspirate microscopy v. bone marrow trephine biopsy microscopy for detection of Mycobacterium tuberculosis infection.

BACKGROUND: Tuberculosis (TB) remains a global health problem. According to the 2013 Global Report on Tuberculosis, 8.6 million people developed TB in 2012 and 1.3 million died from the disease. An estimated 13% of people who developed TB in 2012 were HIV-positive, and 75% of these lived in Africa. While pulmonary TB is the commonest form of Mycobacterium tuberculosis infection, extrapulmonary TB is increasingly being detected in HIV-positive patients. Definitive diagnosis of disseminated TB is a challenge owing to atypical presentations and diagnostic difficulties (negative chest radiograph and sputum microscopy and culture). A rapid diagnosis of disseminated TB is desirable, as early initiation of treatment can reduce mortality. Although TB culture is the gold standard for diagnosis of TB, it has a long turnaround time (up to 6 weeks). OBJECTIVES: To identify a potentially faster and more effective diagnostic strategy for disseminated TB. METHODS: A retrospective 18-month review, conducted at a tertiary hospital, comparing histological findings of an auramine O-stained bone marrow aspiration (BMA) smear and a bone marrow trephine (BMT) biopsy specimen with the gold standard of TB culture. RESULTS: Microscopic examination of BMA smears and BMT biopsy specimens offers a rapid diagnostic strategy, with results available on the same day for the former and within 4 days for the latter. BMT histological examination had a significantly higher detection rate than BMA auramine O staining compared with TB culture. CONCLUSION: We recommend that BMT biopsies remain an essential part of the diagnostic work-up for disseminated TB.

Acquired haemoglobin H disease.

Acquired haemoglobin H disease has been described in various premalignant haematological conditions and is most commonly associated with myelodysplastic and myeloproliferative syndromes. The condition is not restricted to any specific population group or geography. Affected individuals have no family or past history of alpha thalassaemia and these subjects usually suffer from severe uncompensated haemolysis. Extensive mapping and sequence analysis of the alpha globin gene cluster have demonstrated intact alpha globin genes, leading workers to conclude that an acquired in trans mechanism is responsible for the disorder. ATRX gene mutations on the X chromosome have been shown to be instrumental in the suppression of alpha globin gene expression. Despite recent advances in the understanding of its pathogenesis, the precise mechanism of acquired haemoglobin H disease remains a mystery.