disordersofhemesynthesisandironmetabolism

Lee Ellen Brunson, MHS, MLS (ASCP)CM

LSU Health Shreveport

School of Allied Health Professions

Department of Medical Laboratory Science

More Disorders of Heme Synthesis

and Iron Metabolism

(Sideroblastic Anemia)

(Porphyrias)

​

​

Porphyrias

◼ Classified based on:

▪ Clinical presentation

▪ Accumulation in liver – “hepatic”
▪ Accumulation in RBC in BM – “erythropoietic”

▪ Source of enzyme deficiency

▪ Site of enzyme deficiency in heme formation pathway

◼ May be acute or chronic

Clinical manifestations – acute

◼ Abdominal pain
◼ Vomiting
◼ Hypertension
◼ Tachycardia
◼ Neurological involvement

▪ Muscle weakness or paralysis
▪ Seizures
▪ Coma

◼ Psychiatric symptoms

▪ Confusion
▪ Hallucinations
▪ Psychosis

Clinical manifestations – chronic

◼ Cutaneous involvement

▪ Photosensitivity
▪ Skin lesions and blisters
▪ Skin and tissue necrosis
▪ Increased hair growth – hypertrichosis
▪ Loss of skin appendages
▪ Discolored or deformed teeth and/or

gums

◼ Hemolysis
◼ Excretion of heme precursors in urine

and feces: “Port wine urine”

Port wine urine

◼ Urine changes color after sun exposure

Porphyrias, cont.

◼ Laboratory features

▪ Detection of decreased enzyme
▪ Peripheral blood

▪ If present, mild to severe normocytic anemia
▪ Anisocytosis and poikilocytosis
▪ Significant polychromatophilia and NRBCs
▪ RBCs fluoresce with UV light
▪ Normal serum iron and iron storage

▪ BM

▪ Erythroid hyperplasia
▪ Erythroblasts fluoresce red under UV light

Porphyrias, cont.

◼ Prognosis and Therapy

▪ Blood transfusions plus iron chelators

▪ Infusions of heme analogs

▪ BM transplant

▪ Protect skin from sunlight

▪ Minimize toxic effects of protoporphyrin

▪ High doses of β-carotene

▪ Research on gene therapy

Iron Overload

◼ Hereditary: gene mutations
◼ Acquired: transfusion, chronic hemolytic

anemias

◼ Iron acquisition exceeds loss
◼ Stored in cells as ferritin and hemosiderin
◼ System may become overwhelmed, causing

parenchymal organ damage due to
accumulation of free iron

Hemochromatosis

◼ Severe form of iron overload

◼ Can result in marked iron deposition

in macrophages, hepatocytes, skin
cells, cardiac cells, and others

◼ Classically present with:

▪ Bronzed skin pigmentation

▪ Hepatomegaly and jaundice

▪ Diabetes mellitus

◼ Hereditary, secondary, or idiopathic

Laboratory Diagnosis

◼ Four purposes:

▪ To screen
▪ Assess the degree of organ damage
▪ Pinpoint causal mutation, if any
▪ Monitor treatment

◼ Results indicate iron overload

▪ ↑↑↑Serum ferritin
▪ >50-60% transferrin saturation
▪ Excess iron deposits detected upon staining
▪ Liver enzymes usually elevated

Hereditary Hemochromatosis

◼ Etiology and Pathophysiology

▪ ↑ iron absorption in the gut and/or uncontrolled

iron release into plasma pool

▪ Progressive iron overload

▪ Genetic disorder

▪ Prevalence: 1 in 200-250 persons
▪ 1 in 10 Caucasians in the US is a carrier
▪ 5 genes have been implicated: Hepcidin, HFE, TfR2,

ferroportin, HJV

Hereditary Hemochromatosis,
cont.

◼ Clinical Features

▪ 1 in 5000 have clinical symptoms
▪ Symptoms

▪ Chronic fatigue
▪ Arthralgia
▪ Infertility
▪ Impotence
▪ Cardiac disease
▪ Diabetes
▪ Cirrhosis
▪ Hyperpigmentation

Secondary Hemochromatosis

◼ Associated with many conditions

▪ Anemias with ineffective erythropoiesis

(thalassemias, megaloblastic anemias)

▪ Anemia of chronic disease

▪ Transfusion-dependent anemias: Sickle cell

disease, severe thalassemias

Hemochromatosis Treatment

◼ Treat underlying condition, if acquired form
◼ Treat organ/tissue damage
◼ Therapeutic phlebotomy/venesection

▪ For hereditary forms

▪ Each unit removes 250 mg of iron

▪ Hgb monitored periodically; mild anemia is

sought and maintained

◼ Chelation therapy

▪ For acquired/secondary forms