Thalassemia

Rebecca Heming
Overview
● Group of genetic blood disorders
○ Two major types: alpha & beta
thalassemia
■ Multitude of subtypes
● Hemoglobin is made up of alpha &
beta proteins
○ When too little of these proteins are
made, red blood cells do not form
properly and thus cannot carry
enough oxygen, resulting in lifelong
anemia
● Overall: too little hemoglobin &
too few red blood cells
○ Red blood cells are destroyed, which
is what causes anemia
Normal Hemoglobin
Severity
● Severity of thalassemia depends on how many genes are mutated
○ 1- 4 genes can be mutated, with severity increasing as the number of genes mutated increases
Alpha Thalassemia
Mild Alpha Thalassemia: smaller RBC, mild anemia. May have no symptoms

- Loss of 2 alpha-chain genes

Hemoglobin H Disease: severe anemia, associated with other health problems -

enlarged spleen, bone deformities, fatigue

- Loss of 3 alpha-chain genes

Alpha Thalassemia Major: no alpha genes in DNA, which causes the gamma globulin
produced by the fetus to produce an abnormal type of hemoglobin, called hemoglobin
Bart’s. Extremely serious, requiring in utero & lifelong blood transfusions

- Often stillborn or die shortly after birth

- Loss of all 4 alpha globin genes
Beta Thalassemia
Thalassemia Minor: generally no problems, possibly mild anemia

Thalassemia Intermedia: moderately severe anemia, issues with spleen enlargement &
bone deformities. Blood transfusions improve quality of life, but not needed

Thalassemia Major (Cooley’s): complete lack of B protein, requires lifelong blood

transfusions

- Little to no beta globin chains are produced

Complications
● Heart failure & arrhythmias
● Pulmonary abnormalities & pulmonary hypertension]
● Thrombosis
● Leg ulcers
● Enlarged spleen
Iron Overload
● Results from blood transfusions, although can also occur in non-transfused
patients secondary to increased intestinal absorption of dietary iron which occurs
from ineffective erythropoiesis
○ Major cause of morbidity
● Iron is normally transported bound to transferrin, which protects tissues from the
toxic effects of free iron
● Transfusion patients acquire more iron than can be carried by transferrin, resulting
increased levels of free iron
● Use chelation therapy to prevent organ failure and subsequent death
○ Drugs bind with iron and are then excreted through urine
Dietary Iron Recommendations
Non-transfused patients

● Consume moderately low iron diet

○ Avoid iron fortified foods
○ Avoid excess consumptions of meat
● Drink tea or milk with meals
○ Decrease iron absorption

Transfused patients

● Low iron diet not necessary

Foods & Iron Absorption

Decrease Increase
Calcium Vitamin C

Eggs Beta-carotene

Oxalates (tea, chocolate, strawberries, Red meat

basil, etc)

Polyphenols (cocoa, coffee, tea, etc)

Phytates (almonds, lentils, peas, whole

grains, etc)
Other sources of iron
● Vitamins
● Baby foods
● Breakfast cereals
Chelators
● Deferoxamine (Desferal), Deferipone, Deferasirox
○ Abdominal pain, diarrhea, nausea, vomiting
● Chelators bind to iron, which can then be excreted through urine
● Typically started 1-2 years after starting transfusion
Other Potential Nutrition Concerns
● Decreased bone mineralization
○ Need diet rich in vitamin D & calcium
● Diabetes
○ Caused by iron overload in addition to presence of liver disease & infections (common)
● Hepatitis & Liver issues
○ Iron overload leading to cirrhosis
○ Hepatitis A, B, C (from transfusions or other sources)
Anthropometrics
● Pay attention to growth velocity and head circumference
○ Some patients have excessive head growth with only mild anemia
● Mechanism:
○ Thalassemia can cause bone marrow to expand
○ This causes bones to widen, resulting in abnormal bone structure
○ Seen especially in face & skull
○ Also makes bones thin & brittle, which increases risk of broken bones
● Shortening of limbs due to premature fusion of epiphyses
● Ribs and bones become “box-like” and convex
Growth Impairment
Caused by

- Chronic anemia
- Hypermetabolic state caused by ineffective erythropoiesis
- Toxicities from iron chelation therapy
- Endocrinopathies, typically from iron overload
- Nutritional deficiencies from hypermetabolic state & use of chelation agents
- Folate
- Zinc
- Vitamin E
Energy Needs
● Increased?
○ Stunting & growth failure caused by inadequate intake
● Study from 1997
○ 150 kcal/kg & 4 g/kg protein per day with 100%-250% of RDA supplemented
○ Significant weight gain (1.2 kg), height also increased (0.3 cm) but not significantly
○ Weight-for-height Z score changes from -0.94 to 0.05
○ Post discharge, weight gain decreased by height continued to increased, peaking at 4 months
Nutrition Interventions
● Calcium
○ Especially important due to secondary health problems that can affect bone formation and increase
risk of fracture
● Vitamin D
○ May need supplementation
● Folate
○ 1 mg daily for non-transfused patients
● Zinc
○ Associated with frequent comorbidities: growth failure, low bone mineral density, reduced immune
function, glucose intolerance, hypogonadism
○ Needed for bone growth, may need supplement, monitor copper
● Vitamin C
○ Increases iron absorption, but is also an antioxidant
○ Increases iron available for chelation
Recent Study
● Over 20% of patients had deficiencies of:
○ Zinc
○ Vitamin C
○ Vitamin D
○ Copper
○ Vitamin E
○ Calcium
Why are Deficiencies Common?
● Decreased dietary intake/poor appetite
● Elevated losses
● Increased endogenous requirement
● Increased urinary excretion
● Nausea from chelators
● Food intolerances
● Drinking tea instead of energy dense beverage
Key Points for Dietitians
● Monitor growth & head circumference
○ Increased calories and protein?
● Monitor labs, especially micronutrients and vitamins
○ Supplementation
● Encourage calcium intake for bone health
● Help families learn to read nutrition labels
● May need to provide diabetes education
Future Implications
● More research needed!
○ Little is known about energy requirements
○ Does nutrition treatment vary among the different types?
○ How much diet modification is necesary?
References
Cooley's Anemia Foundation. About Thalassemia . http://www.thalassemia.org/learn-about-thalassemia/about-thalassemia/. Accessed
February 1, 2019.

Cunningham E. Is There a Special Diet for Thalassemia? Journal of the Academy of Nutrition and Dietetics . 2016;116(8):1360.
doi:https://doi.org/10.1016/j.jand.2016.06.001.

Goldberg EK, Neogi S, Lal A, Higa A, Fung E. Nutritional Deficiencies Are Common in Patients with Transfusion-Dependent
Thalassemia and Associated with Iron Overload. Journal of Food and Nutrition Research. 2018;6(10):674-681.
doi:DOI:10.12691/jfnr-6-10-9.

Iron Reduction: Chelation Therapy . http://www.irondisorders.org/chelation-therapy. Published July 17, 2009. Accessed February 1,
2019.

UCSF Benioff Children's Hospital . Treating Thalassemia: Chelation. https://doi.org/10.1016/j.jand.2016.06.001. Accessed February 1,
2019.