History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include positive family history and ethnicity from geographic malarial area.

symptoms of anaemia

Fatigue, dizziness, and shortness of breath are useful in determining the severity of the underlying disease if anaemia is present.

splenomegaly

Splenomegaly is more common in non-deletional than deletional haemoglobin H (Hb H) disease.[5][43]

Other diagnostic factors

common

childhood or young adulthood

Because alpha-thalassaemia can have such wide variability in clinical manifestations, patients may present anywhere from in utero, with hydrops fetalis, to any point during adulthood, with an asymptomatic microcytosis. However, those with more severe manifestations will generally present in childhood or young adulthood.

family history of alpha-thalassaemia

Known family history of alpha-thalassaemia will facilitate making the diagnosis.

symptoms of gallstones

Symptoms of bloating, abdominal pain, and wind are suggestive of gallstones, which are fairly common in Hb H disease.

growth retardation

Seen in children with Hb H disease.[5][45]

uncommon

history of prior iron supplementation

Iron supplementation may have been given unnecessarily in the past for a microcytic anaemia.

jaundice

Yellow discoloration of the sclerae, skin, and mucous membranes may be seen in Hb H disease and Hb Constant Spring disease.[5][43]

mild dysmorphic facial features

Maxillary hypertrophy, frontal bossing, prominence of malar eminences.[43][45]​​

extramedullary haematopoiesis

Extramedullary haematopoiesis leading to paraspinal masses has been described.[46][47]

Risk factors

strong

ethnicity from a geographic malarial area

Alpha-thalassaemia is most commonly an inherited disorder, and the epidemiology of the disease corresponds to geographic malarial areas (sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia).[19][20][21]

Alpha(0) variants likely to lead to haemoglobin H (Hb H) disease or alpha-thalassaemia major are most commonly seen in Southeast Asia and also in the Mediterranean.[11]

positive family history

Family history is also important in determining likelihood of disease.

However, the apparent lack of family history does not preclude the presence of alpha-thalassaemia in a newborn. Parents with a mild or even silent clinical phenotype may give rise to offspring with a more severe phenotype (i.e., if both parents are heterozygous for the (--SEA) deletion they have a 25% chance of conceiving a child who has the almost universally fatal homozygous (-- SEA/--SEA) genotype).

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