Case history
Case history #1
A 21-year-old Vietnamese woman presents to her general practitioner to establish care. She emigrated from Vietnam 12 years ago and has not had regular medical care in either country. She reports having chronic fatigue that interferes with her ability to complete her college studies. She has an unremarkable past medical history and has never been pregnant. She is currently sexually active. She has no siblings and her parents have no remarkable medical issues. On physical examination her liver span is 10 cm and her spleen is palpated 5 cm below the left costal margin. No lymph nodes are palpable.
Case history #2
A 26-year-old black woman presents in her thirteenth week of pregnancy with fatigue. She is found to be mildly anaemic with a haemoglobin of 110 g/L (11 g/dL) and an MCV of 75 femtolitres. She is empirically started on iron sulfate tablets and develops significant constipation. Four weeks later she has had no improvement in her haemoglobin and she is referred to haematology. She has never been pregnant previously. There is no known history of anaemia in her family. Her physical examination is unremarkable.
Other presentations
Alpha-thalassaemia presenting after the newborn period has a widely variable clinical presentation, from clinically silent to, less commonly, severe anaemia requiring regular transfusions.[8]
Because alpha-globin chain synthesis is required for fetal oxygenation, patients with deletion of all four alpha-globin genes (--/--) present in utero with alpha-thalassaemia major, almost always leading to death in utero or shortly after birth without intervention.
Patients with haemoglobin H (Hb H) disease (3 alpha-globin gene deletions or 2 deletions plus a point mutation or insertion in the alpha-globin gene) will be identified at birth by elevated Hb Bart (gamma4) in areas in which newborn screening tests for alpha-thalassaemia are performed.[9]
Rarely, Hb H can also lead to hydrops fetalis.[10][11]
Rare inherited mutations in either chromosome 16 or the X chromosome lead to alpha-thalassaemia X-linked intellectual disability syndrome (ATRX) and other abnormalities.[12]
Alpha-thalassaemia can also present rarely as an acquired disorder, most commonly in men in association with myelodysplastic syndrome (ATMDS), and appears to be due predominantly to inactivating somatic mutations of ATRX.[13][14][15]
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