History and exam

Key diagnostic factors

common

symptoms of anemia

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

splenomegaly

Splenomegaly is more common in nondeletional than deletional hemoglobin H (Hb H) disease.[5][44]

Other diagnostic factors

common

childhood or young adulthood

Because alpha-thalassemia 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-thalassemia

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

symptoms of gallstones

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

growth retardation

Seen in children with Hb H disease.[5][46]

uncommon

history of prior iron supplementation

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

jaundice

Yellow discoloration of the sclerae, skin, and mucous membranes may be seen in Hb H disease and Hb Constant Spring disease.[5][44]

mild dysmorphic facial features

Maxillary hypertrophy, frontal bossing, prominence of malar eminences.[44][46]

extramedullary hematopoiesis

Extramedullary hematopoiesis leading to paraspinal masses has been described.[47][48]

Risk factors

strong

ethnicity from a geographic malarial area

Alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia; different genetic subtypes have variable frequencies in each of these areas.[19][20][21]

Alpha(0) variants, which can lead to hemoglobin H (Hb H) disease or alpha-thalassemia major, are most common in Southeast Asia, southern China, and the Mediterranean; prevalence of carriers is 14% in northern Thailand and 5% to 8.8% in southern China.[11]

positive family history

Alpha-thalassemia is a common inherited blood disorder; approximately 5% of the global population carry a defective alpha-thalassemia gene.[16][17]

The apparent lack of family history does not preclude the presence of alpha-thalassemia 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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