Pediatric Module

Anemia
Under Supervision

Prof/Hosny Mohamed El-Masry

By : Group 6
1-Sama Ahmed Abdelbary

2-Salma Sherif Abdelsalam

3-Samira Mohamed Badr

4-Sara Tarek Elsayed Elakraa

5- sara Shaban Ahmed

6-Sara Mohamed Fawzy

Anemia Interpretation in Children
Anemia in children can be indicative of various underlying conditions, including primary blood disorders
such as leukemia or bone marrow failure, as well as secondary pathologies like malabsorption with
hematinic deficiency or chronic renal failure. It is crucial to conduct thorough investigations to confirm
the etiology, even if the cause seems apparent clinically.
Normal Hematological Values
Mean Hb Hematocrit Adult
Cord blood: 16.8 gm% Birth: 50-55% Female: 42%

3 months to 6 years: 12 3 months to 6 years: 36-37% Male: 47%

gm%
7-12 years: 38%
7-12 years: 13 gm%
Clinical Assessment
1 Family History 2 Dietary History 3 Examination
Include history of Sickle Consider iron Physical signs depend
cell disease, deficiency in the diet. on CBC results,
Thalassemia, including pallor of
Spherocytosis, G6PD mucous membranes
deficiency. and other indicators.
Diagnostic Investigations
Key Parameters of Blood Test

Diagnostic investigations for anemia in children involve analyzing various blood parameters such as
hemoglobin, hematocrit, red blood cell count, and mean corpuscular volume.
Blood Film Analysis
Morphological Classifications Pathophysiological Classifications

Microcytic hypochromic, Normocytic Anemia due to blood loss, Hemolytic anemia,

normochromic, and Macrocytic anemia Anemia due to impaired RBC production, and
Anemia of chronic diseases
Anemia Definition and Nutritional
Requirements
1 Definition
Anemia is defined as Hb concentration in
blood below the lower limit of normal or
reduction of RBC volume for age and sex.
2 Nutritional Requirements
Metals, Vitamins, Amino acids, and
Hormones are essential for
erythropoiesis.
M orphologicalClassificationsof Anemia
Microcytic hypochromic anemia
Includes iron deficiency anemia, thalassemia, sideroblastic anemia, and lead poisoning.

Normocytic normochromic anemia

Classification for certain types of anemia.

Macrocytic normochromic anemia

Another classification for specific anemic conditions.
Pathophysiological Classifications of Anemia
Anemia
Anemiadue to Hemolytic anemia Anemia due to Anemia of
bloodloss impaired RBC chronic diseases
Conditions causing production diseases
Acute blood loss, hemolysis of RBCs Associated with
chronic blood loss Defects in RBC chronic diseases
production process like chronic renal
failure, leukemia,
lymphoma, and
myelosclerosis
R ed CellParametersand Blood Film
Analysis
Red cell parameters such as mean corpuscular volume (MCV), mean corpuscular hemoglobin(MCH), and
mean corpuscular hemoglobin concentration(MCHC) are crucial for identifying specific types of anemia
in children.
Anemia in Children: Summary
Understanding the various classifications and diagnostic parameters for anemia in children is essential
for accurate diagnosis and effective treatment. From morphological to pathophysiological
classifications, each aspect plays a vital role in identifying the underlying cause and guiding appropriate
interventions.
Iron Deficiency Anemia
Anemia due to lack of sufficient iron for synthesis of hemoglobin is the most common type of
anemia. It is prevalent in children aged 9-24 months, with a daily requirement of 1 mg of
elemental iron/kg/day up to 15 years. Iron is crucial for the development of red blood cells and
overall brain development in babies.
Iron Absorption and Causes
Absorption
Iron is absorbed in the proximal small intestine
with the help of duodenal proteins at a rate of
10% to 20%. Human milk iron is absorbed 3
times more than cow's milk iron.
Causes
Common causes of iron deficiency anemia
include a diet poor in iron, low birth weight,
cow's milk protein allergy, delayed
supplementation of cereals beyond 5 months,
and chronic blood loss from various sources.
Clinical Features and Investigations
1 Clinical Features
Pallor, pica, koilonychias, irritability, anorexia, tachycardia, hemic murmurs,
tiredness, glossitis, and CNS features like decreased attention and alertness are
common signs of iron deficiency anemia.

2 Investigations

1. CBC: decrease Hb and decrease Serum ferritin

2. decrease Serum iron (Normal 50-15 mcg/dl) and increase Serum iron binding
capacity
3. Peripheral Blood Smear (PBF) shows Microcytic hypochromic, anisocytos
poikilocytosis and nucleated RBC
4. Increase Red cell distribution width (RDW)
5. Reticulocytes normal or increased
6. Thrombocytosis sometimes
7. Bone marrow hyper cellular (erythroid hyperplasia)
Treatmentand R esponse
1 Treatment 2 Response to Iron Therapy
a) 12-24 hours
1. Oral iron therapy-Ferrous salts (4-
6 mg)/kg/day. For 3 months for ▪︎z eplacem entBofBi
ntracellularBenzym esB
correction of Hb and 2 month for ▪︎k li
nicalBresponsebBi
ncreasedBappeti
te,B
body stores repletion) decreased irritability
2. Parenteral iron therapy = Hb b) 36-48 hours :
deficit x weight in kg x 4 (50 mg of
▪︎B oneBm arrow berythroi
d-hyperplasi
a
iron can be given daily I.M.).

3. Diet-Milk consumption should be c) 48-72 hours:

reduced to 500 ml/day or less. ▪︎z eti

culocytosi
sB4-URBdays-i
ncreasedBp bB
4. Iron rich foods should be advised level peak 5-7 days ▪︎S-UBm onths-repleti
onB
like cereals, green leafy of stores.
vegetables, banana, apple, liver,

5. meat
Bloodand fish.
transfusion In severe
anemia-If Hb < 4 gm packed cell 2-

6. 3 ml/kg.
Treat the cause.
Megaloblastic Anemia
Decrease in RBCs synthesis due to defiance of B12 or folic acid.
Causes of Megaloblastic Anemia
B 12

1-decrease intake (severe Malnutrition, vegetarian)

2-decrease absorption (terminal ileum - surgical remove - atrophy due to inflammation as Crops disease)

3-decrease intrinsic factor - Gastrectomy - Pernicious anemia (juvenile or adult type)

4- consumption of B12 as over growth of bacteria

5- decrease stores as ( liver disease)

Folic acid

1_ decrease intake (mal nutrition)

2_ decrease absorption ( non specific "chronic diarrhea ")

3_consumption of folic acid hemolytic anemia

4_ drug (block reductase) sulfonamide- methotrexate

5_ increase requirement (pregnancy )

clinicalpicture
1_Manifiststion of pancytopenia

a_ General manifestations of anemia _fatigue _Tachycardia loss of concentration headache pallor

b- platelet bleeding tendency due to : thrombocytopenia

C-_Luekopenia -infection

2- Git manifestation (Glotitis,stomatitis, diarrhea )

3- ,eurological manifestation B12 only ((degeneration of Shewan cells))

Investigations
1_C B C M acrocyticnorm ochromicanemialeucopenia) hypersegment
T hrom bocytopenia

2_Folic ,B12 serum

3 -Aspiration of BM

4_schilling test

5 FlGlu test 6 detectionantibodiesagaintsof paritalcellsof Stomach

Treatment
1_decrease in B12 and folic acid .

2_decrease folic acid :just folic acid.

Folic acid should be administered orally stat by 5 mg and higher dose is indicated in hemolysis.

Reticulocytosis after 5_7days.

Hemolytic Anemia
Hemolytic anemia is a group of disorders characterized by
the rapid destruction of red blood cells, often surpassing
the bone marrow's production capacity.
Causesand T ypesof Hem olytic Anemia
1 Intrinsic Causes
This includes inherited conditions like sickle cell anemia and thalassemia, leading to
flawed red blood cells.

2 Extrinsic Causes
External factors such as infections, autoimmune disorders, and medications trigger the
destruction of red blood cells.
Symptoms and Diagnosis of Hemolytic
Hemolytic Anemia
Symptoms and Diagnostic Tests

The symptoms of hemolytic anemia include pale skin, jaundice, dark-colored urine, and an enlarged
spleen. Diagnostic tests include complete blood count, peripheral smear, and urine tests to identify
hemoglobin breakdown products.
Treatmentand Com plicationsof
Hem olytic Anemia
Treatment Options Possible Complications
Treatment strategies include blood Complications of hemolytic anemia include
transfusions, corticosteroids, gallstones, blood clots, kidney failure, and
immunosuppressive therapy, and heart failure.
splenectomy in severe cases.
Thalassemia
T halassemiaS yndrome
Structure of HB

Fetal HB :2Alpha +2Gamma chains .

Adult HB:2Alpha +2Beta chains .

Minor adult HB A2: 2Alpha+2Delta chains.

Definition of Thalassemia syndrome : These are heterogenous group of mendelian disorders

characterized by lack of or decreased synthesis of polypeptide chain of hemoglobin (alpha globin chain
or beta globin chain or hemoglobin A "alpha 2 beta 2".

In genetics : 2pairs of genes are responsible for alpha chains formation , on chromosome 16 .

And 2 pairs of genes are responsible for beta chains formation ,on chromosome 11.
Classification of T halassemiaS yndrome
1_Alpha thalassemia

Is classified according to number of genes deleted : 1_silent carrier state "one gene deletion" 2_alpha
thalassemia trait "two genes deletion" 3_hemoglobin H disease "three genes deletion" 4_hydrops
fetalis "four gene deletion"

2_Beta thalassemia

Is classified according to severity of anemia which is based on type of genetic defect:

A/Thalassemia major ."most sever form"

B/thalassemia minor /trait "asymptomatic carrier".

C/thalassemia intermedia "mild".

D/ presence of one normal gene .

Thalassemia Major (Cooley's Anemia)
causes

1_Complete absence of beta chain synthesis or only small amount of beta chain is formed .

2_Excessive formation of alternate HB as fetal HB or HBA2 .

Clinical features

Infant born normally.

1_Anemia appears within 4_6 months.

2_Hepatosplenomegaly.

3_ Thalassemia facies due to expansion of facial bones because of erythroid hyperplasia (frontal bossing
, prominent maxilla, malocclusion of teeth , depressed nasal bridge)

4_ features of iron overload : _ Growth retardation. _Delayed puberty. _DM. _Cardiac failure due to
cardiomyopathy due to iron overload.
Investigations
1_HB estimation <5% gm.

2_RBCs decreased, leukocytosis ,platelet normal .

3_Decreased hematocrit ,MCV ,MCH.

4_increased reticulocytes counts.

5_Peripheral blood film: Microcytic hypochromic anemia , fragmented RBCs , polychromatic.

6_Serum bilirubin increase.

7_HB electrophoresis : Either fetal HB increased 50_98% or HBA2 increased ,HBA1 decreased.

8_ decreased Osmotic fragility.

9_ Increased serum ferritin .

10_X-ray changes: Hand : rectangular appearance of metacarpals, skull hair on end appearance.

BM :normoblastic erythroid hyperplasia.

Thalassemia minor
• HB 10-12 gm.
• alpha gene is normal.
• moderate suppression of beta chain.
• Usually asymptomatic, mild anemia.
• Spleen may be palpable.
• Slight increase of FHB.
• Increased HBA2.
Thalassemia Intermedia
HB between 5_10 gm.

Usually anemia detected around 45 years .

Mild hepatosplenomegaly.

Features between major and minor.

 Hereditary S pherocytosis

Definition Hereditary hemolytic anemia with abnormal

red cell membrane

Pathogenesis Deficiency in structural sceptrin protein of

RBC membrane

Inheritance Autosomal dominant

ChbT …. Iereditary Spherocytosis
Clinical features :

hemolytic anemia.

splenomegaly.

jaundice.

pigment gallstone.

Investigations :

1-Hb..... decrease mild to moderate.

2-Reticulocyte count..... increase 5-20%.

3-EMA(Eosin-5-maleimide binding) test.

4-Microspherocytes.

5-Osmotic fragility..... increased.

Treatment of Hereditary Spherocytosis
• splenectomy after 5 years of age.

• partial splenectomy in child<5 years.

• folic acid supplementation (1mg daily).

• post splenectomy prophylaxis:

1- vaccines for pneumococcus, H. influenza, meningococcus.

2- oral penicillin V (125-250 mg).

Introduction of G6PD

What is G6pd Disease ?

Genetic Disorder G6pd disease is a genetic disorder that effects the red blood cells. Enzyme deficiency .
The disease is caused by a deficiency of the enzyme glucose-6-phosphate dehydrogenase,which
responsible for hexose monophos shunt.

Prevalence

G6pd disease is ( x-linked recessive disorder with obvious symptoms)so more common in males.
heterozygous female appear normal, can affect if she is homozygous Inheritance The disease can be
inherited from carrier mothers.
Causes and Risk factors of G6PD
G6pd disease is primarily caused by an inherited mutation in the G6PD gene. This gene provides
instructions for producing an enzyme called glucose-6-phosphate dehydrogenase, which is responsible
for protecting red blood cells from damage caused by certain substances. In addition to the genetic cause
, there are several risk factors that can trigger symptoms in individuals with G6pd deficiency.

These risk factors include:

1-Certain medications:

such as certain antibiotics, anti malarias, and non steroidal anti inflammatory drugs (NSAIDs)

2-vitamin K , can trigger a reaction in individuals with G6pd deficiency.

3- certain infections , particularly bacterial and viral infections , can cause the destruction of red blood
cells in individuals with G6pd deficiency.

4-Certain foods: some foods , such as fava beens, can trigger a reaction in individuals with G6pd
deficiency .
Symptoms and Diagnosis of G6PD
G6pd disease, also known as glucose-6-phosphate dehydrogenase deficiency, is a genetic condition that
affects the red blood cells,It is more common in males and can cause a range of symptoms in pediatric
patients.

Common symptoms of G6pd disease in pediatric patients include:

1- Sudden Neonatal Jaundice: Yellowing of the skin and eyes ,on set is usually in the first 3 days of life .

2-Sudden pale skin : Reduced red blood cell count can lead to paleness.

3-Dark urine : The breakdown of red blood cells can cause red colored urine.

4-Sudden fever .

5-Rigor and fatigue .

6-Bilateral loin pain.

Diagnosis of G6pd disease is typically done through a blood test to measure G6PD levels. This test can
determine if a patient has reduced or absent G6pd activity, indicating the presence of the condition.
Complications and ManagementG6PD
1- Anemic HF .

2-Acute Renal failure .

3-Complication of Blood Transfusion .

4-Regular monitoring of G6pd levels .

5-Avoiding triggers that can cause hemolytic episodes , such as certain foods or medications .

6-Providing supportive care during hemolytic episodes , such as blood transfusions if necessary.
IVES TIGA TIO N of G6P D
BLOOD DURING ATTACK BLOOD PICTURE;

1- Normocytic normochromic anemia.

2-Increase reticulocytotic Bilirubin.

3-Increase indirect bilirubin.

4-Decrease; hemopexin and haptoglobin URINE.

HEAM-GLI,REA E,ZYME ACTI4ITY ; G6PD E,ZYME LE4EL (2-3 weeks after attack)
Treatment options of G6PD
1- The treatment for pediatric patients with G6pd disease primarily focuses on avoiding tiggers that can
cause a G6PD crisis . This includes certain medications and foods that can lead to the destruction of red
blood cells. In addition to trigger avoidance , supportive care may also be provided to manage symptoms
and complications .

2- supportive packed RBCs transfusion during a cute attack.

3- Washing of the kidney.

Prevention Strategies of G6PD
1- Avoid foods and medication that trigger G6pd deficiency, such as Fava beans, anesthetics, and certain
antibiotics.

2- Carry a G6pd Deficiency cared to alert health care providers of the condition.

3- Consider genetic testing for family members to identify carriers and potential risks.

Genetic Counseling

1- Provide information on the genetic basis of G6PD deficiency and its potential impact on health.

2- Discuss the risks and benefits of genetic testing for family members.

3- Offer support and resources for families with a history of G6PD deficiency.
Aplastic Anemia
Aplastic anemia is characterized by the failure or
suppression of multipotent myeloid stem cells, resulting
in pancytopenia - a condition characterized by low counts
of red blood cells, white blood cells, and platelets.
Causes of Aplastic Anemia
Idiopathic
Aplastic anemia can occur
without an identifiable
cause, making it challenging
to determine the underlying
reason.
S econdary causes
Exposure to myelo-toxic
drugs, chemicals, infections,
irradiation, and inherited
diseases are common
secondary causes of aplastic
anemia.
Hematological Disorders
Certain inherited diseases
such as Fanconi anemia and
Diamond Blackfan anemia
can lead to aplastic anemia.
ClinicalFeaturesof Aplastic Anemia
1 GradualO nset
The onset of aplastic anemia is gradual, often leading to overlooked symptoms at
initial stages.

2 Anemia and Infections

Patients may present with anemia and an increased susceptibility to infections due to
reduced white blood cell count.

3 Bleeding T endency
Thrombocytopenia in aplastic anemia can lead to prolonged bleeding and easy bruising.
DifferentialDiagnosisof Aplastic Anemia
1 Idiopathic 2 Leukemia 3 M yeloid M etaplasia
T hrom bocytopen
A type of cancer that A group of rare bone
ic P urpura(IT P)
affects the bone marrow disorders
A condition marrow, leading to marked by abnormal
characterized by low abnormal white blood blood cell production.
platelet levels, leading cell production.
to purpura and
prolonged bleeding.
HematologicalInvestigationsfor
Aplastic Anemia
Common Investigation Tests

Diagnosing aplastic anemia involves a series of hematological tests, including complete blood count
(CBC), peripheral smear, and bone marrow aspiration for detailed cell analysis.
Treatment of Aplastic Anemia
B one M arrow
Transplantation
Transplantation is the
preferred treatment method
for aplastic anemia, aiming
to restore normal bone
marrow function.
S upportive T herapy Growth Factorsand
Im m unotherapy
Blood transfusions,
antibiotic therapy, and Stimulating factors like G-
immunosuppressive drugs CSF and erythropoietin,
form a crucial part of along with immunotherapy,
supportive therapy. play a vital role in managing
the disease.
 Cases of Anemia
BY : Selwan Mohamed Ebrahim

B Y : S himaaA hmed M ohamed

Case 1
A 2 yearsold female presented with upperrespiratory tractinfection,shelooked pale.S he was
drinking 3 pintsofcow'smilkCdayandshe wasavery fussy eater,refusing meat.shestarted eating
soilw hen playingin the garden(pica).C B C: HB 7 gmCdl,M C V 54 fl,M C H 16 pg.

1-What is your diagnosis?

2-W hatfurtherinvestigationsw ould you request?

3-Treatment of this case?

Answers of Case 1
1-Iron deficiency anemia

2- _S erum ferritin ↓↓ _S erum iron ↓↓ _S erum iron binding capacity ↑↑ _P eripheralBlood S mear(P BF)
shows microcytichypochromic,anisocytosis,poikilocytosisand nucleated R B C. _R ed celldistribution
width(R D W ) ↑↑ _R eticulocytesnormalorincreased _T hrom bocytosissometimesand Bone marrow
hypercellular

3- Oral iron therapy.

R eplacingsome ofthe milk withironrichfood.

Case 2
A 4-year-old boy presented to the ER with epistaxis,highfeverand cough. O n examination:the child
lookstoxic,pale tem perature 39,wt 15 kg,height 80 cm. T hereisahyperpigmented rash overthe
back,chestexaminationrevealed crepitationsallover.N o palpablespleen orliver.Hbis6 gCdl,
platelets6000Ccm m, W B Cs 3800Ccm m,reticulocytes1 %.

1-What is your diagnosis?

2-Differential Diagnosis?

3-What is the further investigations?

Answersof Case 2
1- Aplastic anemia.

2-IT P _aleukemicleukemia_M yeloid metaplasia.

3-Bone marrow dry tap or hypocellular marrow or aplastic marrow.

Case 3
A 9-month-old baby girl of Mediterranean descent is brought in by her father as she appears pale and has not been
gaining weight. The child also has a "lump" in her upper left abdomen. On physical examination, the girl is noted to be
lethargic. Her skin is pale and her sclera has a tinge of yellow. The zygomatic bones are disproportionably larger than
the rest of her facial bones. The spleen is palpable 5 cm below the left costal margin. CBC - Ib (g/L) ↓, aCV ↓, w.C
count ↑, weticulocyte Count ↑, W.C b, tLT b.

1-What is your diagnosis?

2-List another cause for microcytic hypochromic anemia?

3-W hatisthe mainline of management ofthiscase?

4-What is the most diagnostic investigation?

Answersof Case 3
1- Chronic hemolytic anemia most probably B-thalassemia major.

2-iron deficiencyanemia,sideroblasticanemia,lead poisoning,anemiaofchronic disease.

3-lifelong packed RBCs transfusion with iron chelating agent.

4-Hb electrophoresis : Either fetal Hb increased 50 to 98% or Hb A 2 increase, Hb A 1 decreases.

Case 4
A 1-yearold boy presented to the ER withlethargy andsevere pallor.He had atinge ofjaundice.O CE
hisHR was160 BCM and R R was65Cm. T he baby wasquite welltillthe m otherintroduced beans
recentlyinto hisfood yesterday.

1-What is your possible diagnosis?

2-W hatisthe m ostspecifictestto confirm the diagnosis?

3-What is your treatment?

Answersof Case 4
1-Acute hemolysis most probably G6PD deficiency.

2-Enzyme activity (Assay of G6PD Enzyme)

Blood film : RBC shows Heinz bodies

3-avoid oxidantstress_blood transfusionifsevereanemia.

MCQs of Anemia
S hams Esam M ohamed .

Suhila Wali Eldin Mohamed.

M CQ 1
1-Iron deficiency anemia can be caused by all the following except

a-Bone marrow infiltration

b-Low birth weight

c-A ncylostomiasis

d-Prolonged exclusive breastfeeding's

e-C hronic diarrhea

2-Which of the following is least necessary for red call production?

a-Folate

b-Vitamin C

c-Calcium

d- Iron

e-T hyroid horm ones

MCQ 2
3. Hematologicalinvestigationsinachild with B thalassemiamajorrevealallthefollowing except:

a-Normocytic normochromic anaemia

b-R eticulocytosis

c-Increased serum iron

d-Erythroid hyperplasia of bone marrow

e-Raised HbF

4-W hich ofthefollowingisa m ore com m on cause of deathin Beta

thalassemia major?

a-Diabetesmellites

b-Renal failure

c-Heartfailure

d-Intestinal obstruction

e-Cirrhosis
MCQ 3
5.Allthefollowing are com m only observedinaplasticanemiaexcept:

a-Increased ability to bleeding

b-S plenomegaly

C-Decreased reticulocytes in peripheral blood

d-R ecurrentInfections

e-Normocytic normochromic anemia

6-Term new born has blood volume of:

a)110ml/kg

b)20mlCkg

c)85ml/kg

d)60mlCkg
MCQ 4
7-T he deficiencyanemiaism ostlikely to be caused by:

a) Parasitic infection.

b) Hematuria

c) Artificial feeding.

d)Allofftheabove.

8-All off the following diseases cause hemolytic anemia except:

a)M alaria.

b)SLE

c)Iron deficiencyanemia.

d)DIC.
MCQ 5
9-Iron deficiency anemia is characterized by the following except:

a)M icrocytichypochromicanemia.

b) Decreased iron binding capacity.

c)Decreasedserum ferritin.

d)pica

10-M egaloplasticanemiaoccursdue to:

a)folic acid deficiency.

b)zinc deficiency.

c)copper deficiency.

d)B_thalassemia.
MCQ 6
11-W hich ofthefollowingisnot true about megaloblasticanemia:

a) It's caused by B12 or folate nutritional deficiency.

b)bone marrow appearanceisidenticalin B 12 orfolate deficiency.

c) It's caused by defective DNA synthesis.

d)B12 deficiency may be associated with neurological manifestations.

12-Concerning hereditary spherocytosis:

a)A utosomaldominantininheritance.

b) splenectomy.

c)liability to pigmentary gallstones.

d)All off the above.

M CQ 7
13-The CBC of a patient with thalassemia may show the following except:

a)microcytosis.

b)Acanthocytosis.

c)hypochromia.

d) increased reticulocyte.

14-T halassemiamajorischaracterized by allofthefollowing except:

a)bony hyperplasia.

b)A uto-splenectom y.

c) mongoloid features.

d)marked hepatosplenomegaly.
MCQ End
15-A plasticanemiacan besecondary to:

a) Radiation.

b) hepatitisA.

c) parvovirus B-19.

d)Allofftheabove.
Answers of MCQ
1 .bone marrow infiltration

2. calcium

3. norm ocyticnorm ochromicanemia

4. Heart failure

5. S plenomegaly

6. 85ml/kg

7. Alloftheabove

8. Iron deficiency anemia

9. Decreased Iron binding capacity

10. Folic acid deficiency

11.It'scaused by defective DN A synthesis

12. All of the above

13. Acanthocytosis

14. Auto-splenectomy

15. Alloftheabove