الـرحيــم الـرحمـن اللــه الـرحيــم بســم الـرحمـن اللــه بســم

Blood diseases.Blood diseases.Dr. Abed M. Al Hazmi.Dr. Abed M. Al Hazmi.

Associated prof. of pediatrics.Associated prof. of pediatrics.King A/Azziz University Jeddah King A/Azziz University Jeddah

KSA.KSA.

Definition of ANEMIA:Definition of ANEMIA:Anemia is defined as Anemia is defined as

reduction in red blood cell reduction in red blood cell mass, below 2SD of the range mass, below 2SD of the range

of values for that age, and of values for that age, and sex found in healthy person, sex found in healthy person,

i.e. (<-2SD). i.e. (<-2SD).

Normal Values ( mean and lower limit of normal (-2 SD)),Normal Values ( mean and lower limit of normal (-2 SD)),for Hemoglobin, and Mean Corpuscular Volume (MCV) at various for Hemoglobin, and Mean Corpuscular Volume (MCV) at various

Ages.Ages.

Hemoglobin (g/dl) Hemoglobin (g/dl) MCV (fl) Hematocrit (%).MCV (fl) Hematocrit (%). AgeAge Mean Mean -2SD-2SD Mean -2SDMean -2SD Mean -2SDMean -2SD ________________________________________________________________________________________________________________________________________ Cord blood 16.5Cord blood 16.5 13.513.5 108108 9898 5151 42.42. 1 WK1 WK 17.5 17.5 13.513.5 107107 8888 5454 42.42. 2 WK2 WK 16.5 16.5 12.512.5 107107 8686 5151 39.39. 1 mo 14.01 mo 14.0 10.010.0 104104 8585 4343 31.31. 2 mo 11.52 mo 11.5 9.09.0 9696 7777 3535 28.28. 3-6mo 11.53-6mo 11.5 9.59.5 9191 7474 3535 29.29. 0.5-2yr0.5-2yr 12.0 12.0 10.510.5 7878 7070 3636 33.33. 2-6yr2-6yr 12.5 12.5 11.511.5 8181 7575 3737 34.34. 6-12YR 13.56-12YR 13.5 11.511.5 8686 7777 4040 35.35. 12-18YR12-18YR Female 14.0Female 14.0 12.012.0 9090 7878 4141 36.36. Male 14.5Male 14.5 13.013.0 8888 7878 4343 37.37. 18-49yr18-49yr female 14.0female 14.0 12.012.0 9090 8080 4141 36.36. Male 15.5Male 15.5 13.513.5 9090 8080 4747 41.41.

Classification of anemia:Classification of anemia:

A useful classification of the anemia A useful classification of the anemia is to divided anemia into three large is to divided anemia into three large groups by the RBC CELL Mean groups by the RBC CELL Mean Corpuscular Volume (MCV).Corpuscular Volume (MCV).

Microcytic Macrocytic NormocyticMicrocytic Macrocytic Normocytic MCV < 76MCV < 76 MCV > 96MCV > 96 MCV 76-96 femto.MCV 76-96 femto.

Iron deficiency Folate deficiency Hemolytic anemia'sIron deficiency Folate deficiency Hemolytic anemia's ThalassemiaThalassemia Vit. B12 Deficiency Anemia of chronic dis.Vit. B12 Deficiency Anemia of chronic dis. Lead poisoningLead poisoning cong. Hypoplastic Acute blood losscong. Hypoplastic Acute blood loss Sideroblastic anemiaSideroblastic anemia anemia.(D.B.S) Aplastic anemia.anemia.(D.B.S) Aplastic anemia. Anemia of chronicAnemia of chronic Preleukemia.Preleukemia. SCA. G6PD.SCA. G6PD. DiseaseDiseaseLiver diseaseLiver disease Fanconi anemia.Fanconi anemia. Copper deficiencyCopper deficiency HypothyroidismHypothyroidism Infiltrative process.Infiltrative process. Thiamine deficiency.Thiamine deficiency.

Others Classifications of Anemia:Others Classifications of Anemia:

anemia may be classified into the following 3 anemia may be classified into the following 3 primary categories:primary categories:

1- Decreased red cell production1- Decreased red cell production 2- Increased red cell destruction (hemolysis)2- Increased red cell destruction (hemolysis) 3- Anemia due to blood loss. 3- Anemia due to blood loss.

Clinical features of anemia:Clinical features of anemia: NB: When oxygen delivery by RBC to tissues is decrease: NB: When oxygen delivery by RBC to tissues is decrease:

the body responds by compensatory mechanism include:the body responds by compensatory mechanism include: 1- Increase cardiac output 2- Increase 2-3 DPG.1- Increase cardiac output 2- Increase 2-3 DPG.

(diphosphoglycerate)(diphosphoglycerate) 3- Increase EPO production 4- Shift of blood to vital organs.3- Increase EPO production 4- Shift of blood to vital organs.

The clinical effects of anemia are The clinical effects of anemia are influenced by 4 major factors:influenced by 4 major factors:

1- The speed of onset 2- Severity of anemia.1- The speed of onset 2- Severity of anemia. 3- Age of onset 4- The HGB – O2 dissociation 3- Age of onset 4- The HGB – O2 dissociation

curve.curve.

Symptoms:Symptoms: 1- Shortness of breath (particularly on exercise).1- Shortness of breath (particularly on exercise). 2- Weakness.2- Weakness. 3- Lethargy.3- Lethargy. 4- Anorexia.4- Anorexia. 5- Headache.5- Headache. 6- Heart failure.6- Heart failure. 7- Palpitation ( older children & Adult ).7- Palpitation ( older children & Adult ).

Signs:Signs: General signs:General signs: 1- Pallor (mucous membrane). Present when Hgb <10g/dl.1- Pallor (mucous membrane). Present when Hgb <10g/dl. 2- Hyper dynamic circulation ( tachycardia, bounding pulses).2- Hyper dynamic circulation ( tachycardia, bounding pulses). 3- Features of heart failure.3- Features of heart failure. 4- Failure to thrive.4- Failure to thrive.

Specific signs:Specific signs: 1- Jaundice ( Hemolytic anemia ).1- Jaundice ( Hemolytic anemia ). 2- Leg ulcer ( SCA ). 2- Leg ulcer ( SCA ). 3- Koilonychias ( spoon nail ). 3- Koilonychias ( spoon nail ). 4- Bone deformities ( Thalassemia).4- Bone deformities ( Thalassemia). 5- Smooth red painful tongue ( vit. B12 Def. ).5- Smooth red painful tongue ( vit. B12 Def. ).

Anemia in the Neonate & First Anemia in the Neonate & First three months of age:three months of age:

Some types of anemia occur at birth or in Some types of anemia occur at birth or in early infancy. They are due to early infancy. They are due to

Physiological, Physiological, Acquired, Acquired, Inherited,Inherited,

A two months old infant seen in ER, because of A two months old infant seen in ER, because of one day history of S.O.B. and cough. one day history of S.O.B. and cough.

He is a product of S.V.D, full term pregnancy.He is a product of S.V.D, full term pregnancy. A CBC was done showed:A CBC was done showed: WBCWBC 15000/mm3.15000/mm3. RBCRBC 4.5 x 10 12/mm3.4.5 x 10 12/mm3. HgbHgb 8.2 g/dl.8.2 g/dl. MCVMCV 80 pf.80 pf. PlateletPlatelet 250000/mm3.250000/mm3.

What is your comment on this CBC ?What is your comment on this CBC ? What is your management ?What is your management ?

Physiological anemia & Anemia of Physiological anemia & Anemia of prematurityprematurity

Physiological anemia:Physiological anemia: developed in full term developed in full term baby by age of 6 – 12 wks with Hb ( 8.0 – 11 g/dl ).baby by age of 6 – 12 wks with Hb ( 8.0 – 11 g/dl ).

Anemia of prematurity:Anemia of prematurity: developed preterm developed preterm baby by age of 4 -6 wks with Hb level ( 4 – 10 g/dl ).baby by age of 4 -6 wks with Hb level ( 4 – 10 g/dl ).

Mechanisms of these anemia:Mechanisms of these anemia: 1- Cessation of erythropoietin (EPO) production.1- Cessation of erythropoietin (EPO) production. 2- Shortened survival of fetal RBC.2- Shortened survival of fetal RBC. 3- Expansion of blood volume due to rapid wt. gain.3- Expansion of blood volume due to rapid wt. gain. 4- After birth the ratio of HbF/HbA decreased & (2-3 DPG) increased, this 4- After birth the ratio of HbF/HbA decreased & (2-3 DPG) increased, this

result in increased O2 delivery to tissue and decreased hypoxia which result in increased O2 delivery to tissue and decreased hypoxia which stimulate EPO production. stimulate EPO production.

A two months old infant seen in ER, because of A two months old infant seen in ER, because of one day history of S.O.B. and cough. one day history of S.O.B. and cough.

He is a product of S.V.D, full term pregnancy.He is a product of S.V.D, full term pregnancy. A CBC was done showed:A CBC was done showed: WBCWBC 15000/mm3.15000/mm3. RBCRBC 4.5 x 10 12/mm3.4.5 x 10 12/mm3. HgbHgb 8.2 g/dl.8.2 g/dl. MCVMCV 80 fl.80 fl. PlateletPlatelet 250000/mm3.250000/mm3.

What is your comment on this CBC ?What is your comment on this CBC ? What is your management ?What is your management ?

Clinical manifestations:Clinical manifestations: Pure physiological anemia of infancy almost always fully Pure physiological anemia of infancy almost always fully

compensated with no symptoms or signs, unless there is/are other compensated with no symptoms or signs, unless there is/are other process associated e.g. neonatal infection, blood loss, hemolysis.process associated e.g. neonatal infection, blood loss, hemolysis.

Therapy:Therapy: Usually required no therapy other than ensuring that diet Usually required no therapy other than ensuring that diet

contains the essential nutrients for normal hematopoiesis contains the essential nutrients for normal hematopoiesis as folic ac., & iron.as folic ac., & iron.

Transfusion when the baby is not growing properly, apneic Transfusion when the baby is not growing properly, apneic spell, bradycardia, infections.spell, bradycardia, infections.

Recombinant human EPO, plus iron & folic ac. When blood Recombinant human EPO, plus iron & folic ac. When blood transfusion is not possible. transfusion is not possible.

Acquired anemia in the neonate:Acquired anemia in the neonate: Blood loss:Blood loss:

A- Obstetric as a cause of blood loss:A- Obstetric as a cause of blood loss: 1- placenta previa.1- placenta previa. 2- Abrupt placenta.2- Abrupt placenta. 3- Hematoma of the umbilica cord.3- Hematoma of the umbilica cord. 4- Rupture of the umbilical cord.4- Rupture of the umbilical cord.

B- Occult blood loss:B- Occult blood loss: 1- Fetomaternal bleeding:1- Fetomaternal bleeding:

A- Placenta malformation.A- Placenta malformation. B- Obstetric procedure ( Traumatic amniocentesis, B- Obstetric procedure ( Traumatic amniocentesis,

external or internal cephalic version, breech delivery ).external or internal cephalic version, breech delivery ). C- Spontaneous.C- Spontaneous.

C- Fetoplacenta bleeding:C- Fetoplacenta bleeding: 1- Chorioangioma, Choriocarcinoma.1- Chorioangioma, Choriocarcinoma. 2- Cesarean section ( infant hold above placenta).2- Cesarean section ( infant hold above placenta). 3- Tight nucal cord or occult cord prolapse>3- Tight nucal cord or occult cord prolapse>

This is the picture of twin delivery:This is the picture of twin delivery:What is your description ?What is your description ?

What are the complications in the first & second twin?What are the complications in the first & second twin?

D- Twin – Twin Transfusion.D- Twin – Twin Transfusion.

E- Hemolysis:E- Hemolysis: 1- Rh, ABO, & minor blood gr. 1- Rh, ABO, & minor blood gr.

Incompatibility.Incompatibility. 2- Infection, DIC, Vit. E deficiency.2- Infection, DIC, Vit. E deficiency.

Hereditary RC Disorders:Hereditary RC Disorders: A- Metabolic defect as G6PD, Pyruvate kinase A- Metabolic defect as G6PD, Pyruvate kinase

def.def. B- RBC membrane defect as spherocytosis, B- RBC membrane defect as spherocytosis,

elleptocytosis, somatocytosis.elleptocytosis, somatocytosis.

Hemoglobinopathies:Hemoglobinopathies: A- Alfa and gamma thalassemia syndrome.A- Alfa and gamma thalassemia syndrome. B- Alfa and gamma chain structural abnormal.B- Alfa and gamma chain structural abnormal.

Diminished RBC production:Diminished RBC production: A- Diamond – Blackfan Syndrome.A- Diamond – Blackfan Syndrome. B- Congenital leukemia.B- Congenital leukemia. C- Infection ( specially Rubella, Parvovirus).C- Infection ( specially Rubella, Parvovirus). D- Osteopetrosis.D- Osteopetrosis.

Nutritional Anemia:Nutritional Anemia:( due to deficiency of substances essential for erythropoiesis)( due to deficiency of substances essential for erythropoiesis)

A- A- Iron deficiency anemia:Iron deficiency anemia: (very common). (very common). (Uncommon problem in childhood).(Uncommon problem in childhood). B- B- Megaloblastic anemia:Megaloblastic anemia: due to deficiency of due to deficiency of

Vit B12 or folic acid. Vit B12 or folic acid. CC- - Anemia due to protein malnutrition:Anemia due to protein malnutrition: D- Vit C deficiency anemia:D- Vit C deficiency anemia: (associated with (associated with

scurvy or pyridoxine deficiency).scurvy or pyridoxine deficiency).

Test nameTest name Result Result Refer. Range Refer. Range Unit.Unit. ______________________________________________________________________________________________________________________ WBC ( White blood Cell Count). WBC ( White blood Cell Count). 6.7 6.7 4.5 - 11.54.5 - 11.5 K/ulK/ul

RBC ( Red blood Cell Count ).RBC ( Red blood Cell Count ). 3.15 3.15 4.00 – 6.00 4.00 – 6.00 M/ul M/ul .. Hemoglobin ( Hb ).Hemoglobin ( Hb ). 8.5 8.5 12 – 16. 12 – 16. g/dl g/dl

Hematocrit ( HCT ).Hematocrit ( HCT ). 30.00 30.00 36 – 54 36 – 54 % .% .

Mean Corpuscular Volume) MCV.Mean Corpuscular Volume) MCV. 60.0060.00 70 – 8070 – 80 fl.fl.

Mean Corpuscular Hb MCHMean Corpuscular Hb MCH 23.0023.00 27 – 3227 – 32 pg.pg.

Mean Cor. Hb Conc. MCHCMean Cor. Hb Conc. MCHC 28.0028.00 32- 3632- 36 %.%.

RDW ( RBC distribution width )RDW ( RBC distribution width ) 17.117.1 11.5 – 14.511.5 – 14.5 %.%. ( MCV/RBC ).( MCV/RBC ).

Platelets ( PLT )Platelets ( PLT ) 240240 150 – 450 150 – 450 K/ul. K/ul.

1- Comment on this CBC.1- Comment on this CBC. 2- What is your most likely diagnosis ?.2- What is your most likely diagnosis ?.

Iron Deficiency AnemiaIron Deficiency Anemia( Is the most common anemia in infancy & childhood )( Is the most common anemia in infancy & childhood )

Etiology:Etiology: 1- Inadequate intake of Iron:1- Inadequate intake of Iron:

A- Prolonged breast feeding. Rare before age of 6 mon.A- Prolonged breast feeding. Rare before age of 6 mon. B. Preterm baby ( low birth weight ) & Unusual perinatal blood lossB. Preterm baby ( low birth weight ) & Unusual perinatal blood loss C- Poverty.C- Poverty.2- Blood loss:2- Blood loss:

A- Occult bleeding from GIT as Peptic ulcer, Meckel diverticulum's, Polyps, heamangioma, A- Occult bleeding from GIT as Peptic ulcer, Meckel diverticulum's, Polyps, heamangioma, Inflammatory bowel disease, hookworm infest.Inflammatory bowel disease, hookworm infest.B- In some areas occult blood loss from GIT due to consumption of whole cow's milk B- In some areas occult blood loss from GIT due to consumption of whole cow's milk ( exposure to a heat-labile protein ).( exposure to a heat-labile protein ).

3- Defective absorption of Iron:3- Defective absorption of Iron: A- Malapsorption syndrome.A- Malapsorption syndrome.

B- Excess phosphate & phytate in diet e.g. cereals.B- Excess phosphate & phytate in diet e.g. cereals.C- Achlorhydria ( ).C- Achlorhydria ( ).

4- Increase demand for iron:4- Increase demand for iron:A- Rapid growing premature and growing children.A- Rapid growing premature and growing children.B- Menstruating females.B- Menstruating females.C- Convalescence from disease. C- Convalescence from disease.

Clinical picture:Clinical picture: 1- Pallor is the most important sign of anemia.1- Pallor is the most important sign of anemia. 2- Compensatory mechanisms ( in mild & moderate IDA Hb 6-10 g/dl).2- Compensatory mechanisms ( in mild & moderate IDA Hb 6-10 g/dl).

A- Increased level of 2,3 DPG ( diphospho – glycerate ).A- Increased level of 2,3 DPG ( diphospho – glycerate ). B- Shift of the oxygen dissociation curve. B- Shift of the oxygen dissociation curve. 3- Irritability, pica( pagophagia), and anorexia in severe anemia Hb <5 g/dl.3- Irritability, pica( pagophagia), and anorexia in severe anemia Hb <5 g/dl.4- Iron deficiency with or without anemia have effects on neurologicl and intellectual 4- Iron deficiency with or without anemia have effects on neurologicl and intellectual

function asfunction asattention span, alertness, and learning in both children & adolescent.attention span, alertness, and learning in both children & adolescent.

5- Enlargement of the spleen in 10%.5- Enlargement of the spleen in 10%.6- Angular stomatitis, red glazed tongue.6- Angular stomatitis, red glazed tongue.7- Nails are brittle, striated and loss their luster, in severe anemia there is spooning 7- Nails are brittle, striated and loss their luster, in severe anemia there is spooning

of nails.of nails.8- Hemic mur. In severe anemia.8- Hemic mur. In severe anemia.

Investigations: Investigations: ( follow a sequence)( follow a sequence) Hb & RBC are reduced. And disappearing of B.M. hemosiderin.Hb & RBC are reduced. And disappearing of B.M. hemosiderin. S. Ferritin decreased.S. Ferritin decreased. Iron-binding capacity of the serum (s. transferrin) Increased.Iron-binding capacity of the serum (s. transferrin) Increased. WBC are normalWBC are normal Platelet Increased (in severe IDA Decreased)Platelet Increased (in severe IDA Decreased).. B.M. Hypercrllular with erythrioid hyperplasia.B.M. Hypercrllular with erythrioid hyperplasia.

AS the deficiency of iron progress the RBCAS the deficiency of iron progress the RBC 1- Become small (Microcytic), Decrease their Hgb content (Hypochromic).1- Become small (Microcytic), Decrease their Hgb content (Hypochromic). 2- RBCs become deformed (Poikilocytosis).2- RBCs become deformed (Poikilocytosis). 3- Increase red cell distribution width (RDW).3- Increase red cell distribution width (RDW).

Differential diagnosis:Differential diagnosis: IDA Should be differentiated from:IDA Should be differentiated from: 1- Thalassemia Trait.1- Thalassemia Trait. 2- Lead poisoning.2- Lead poisoning. 3- Sideroblastic anemia.3- Sideroblastic anemia. 4- Chronic diseases.4- Chronic diseases. 5- Copper deficiency.5- Copper deficiency. 6- Hemoglobin E.6- Hemoglobin E. 7- Pyridoxine deficiency.7- Pyridoxine deficiency.

Differential diagnosis:Differential diagnosis: 1- Alfa & Beta Thalassemia trait.1- Alfa & Beta Thalassemia trait. Hb electrophoresis ( Level of Hb A2 & Hb F are increased ).Hb electrophoresis ( Level of Hb A2 & Hb F are increased ). 2- Lead poisoning ( level of lead increased ).2- Lead poisoning ( level of lead increased ). 3- Thalassemia major Hemolytic manifestations.3- Thalassemia major Hemolytic manifestations. 4- Pyridoxin deficiency ( V.B6 level decrease ).4- Pyridoxin deficiency ( V.B6 level decrease ). 5- Chronic disease ( S.iron & Iron-binding capacity are reduced 5- Chronic disease ( S.iron & Iron-binding capacity are reduced

but but S. ferritin increased.S. ferritin increased.

Treatment:Treatment: Oral administration of Ferrous salts ( Sulfate, Gluconate, Oral administration of Ferrous salts ( Sulfate, Gluconate,

Fumarate )Fumarate ) 4-6 mg/kg of elemental iron in three divided doses.4-6 mg/kg of elemental iron in three divided doses. Iron dextran IM Iron dextran IM Vit C Increases absorption of Iron from food.Vit C Increases absorption of Iron from food. Stop bleeding and treat parasitic infestation.Stop bleeding and treat parasitic infestation. Blood transfusion is indicated when:Blood transfusion is indicated when:

1- Severe anemia ( Hb < 4g/dl).1- Severe anemia ( Hb < 4g/dl).2- Anemia associated with infection that may interfere with 2- Anemia associated with infection that may interfere with iron absorption.iron absorption.

Family education and diet to prevent IDA in infancy. Family education and diet to prevent IDA in infancy.

Response to iron therapy:Response to iron therapy: 12 – 24 hr. : replacement of intracellular iron enzymes ( dec. 12 – 24 hr. : replacement of intracellular iron enzymes ( dec.

irritability, increase appetite ).irritability, increase appetite ). 36 – 48 hr. : Initial bone marrow response ( erythroid 36 – 48 hr. : Initial bone marrow response ( erythroid

hyperplasia ).hyperplasia ). 48 – 72. hr. : Reticulocytosis.48 – 72. hr. : Reticulocytosis. 4 - 30 days : Increase in Hb ( 0.5g/dl/24 hr.4 - 30 days : Increase in Hb ( 0.5g/dl/24 hr. 1 – 3 months : Repletion of iron stores1 – 3 months : Repletion of iron stores. .

Megaloblastic AnemiaMegaloblastic Anemia Vitamin B-12 Deficiency:Vitamin B-12 Deficiency: Requirements: 1-2 mic.g/d.Requirements: 1-2 mic.g/d. Sources: Animal products ( liver, Kidney).Sources: Animal products ( liver, Kidney). Absorption: Combined with IF absorbed in the Absorption: Combined with IF absorbed in the

terminal ileum.terminal ileum. Functions: Essential for hemopoiesis & NS Functions: Essential for hemopoiesis & NS

integrity.integrity. Storage: 2 mg. are stored in the liver (sufficient Storage: 2 mg. are stored in the liver (sufficient

for 2-4 yr.).for 2-4 yr.).

Causes of Vit.B-12 Deficiency:Causes of Vit.B-12 Deficiency: A- Poor dietary intake. Rare in children A- Poor dietary intake. Rare in children ( poverty & ( poverty &

Vegan).Vegan).

B- Gastric causes. Rare in children.B- Gastric causes. Rare in children.1- Pernicious anemia ( meanly in adult).1- Pernicious anemia ( meanly in adult).2-Congenital lack or abnormal intrinsic factor (IF).2-Congenital lack or abnormal intrinsic factor (IF).3- Total or partial gastrectomy.3- Total or partial gastrectomy.

C- Intestinal causes. Is the usually causes in children.C- Intestinal causes. Is the usually causes in children.1- Intestinal stagnant synd. Jejunal devirticulosis,1- Intestinal stagnant synd. Jejunal devirticulosis, blind- loop stricture, ect (B12 utilization by blind- loop stricture, ect (B12 utilization by bacteria).bacteria).2- Chronic tropical sprue.2- Chronic tropical sprue.3- Ileal resection & Cohn's disease.3- Ileal resection & Cohn's disease.

D- Congenital deficiency of Vt.B12 carrier proteins.D- Congenital deficiency of Vt.B12 carrier proteins.Transcobalamin Def. ( Tarnscobalamin II ).Transcobalamin Def. ( Tarnscobalamin II ).

E- Others: (rare without clinical importance).E- Others: (rare without clinical importance).Celiac dis. Sever pancreatitis, HIV infection. Celiac dis. Sever pancreatitis, HIV infection.

Clinical manifestations: Clinical manifestations: The onset usually The onset usually insidious.insidious.

1- Mild jaundice (due to ineffective erythropoiesis).1- Mild jaundice (due to ineffective erythropoiesis). 2- Glossitis ( a beefy-red, sore tongue).2- Glossitis ( a beefy-red, sore tongue). 3- Angular stomatitis.3- Angular stomatitis. 4- Signs of malabsorption with wt. loss.4- Signs of malabsorption with wt. loss. 5- Purpura due to thrombocytopenia.5- Purpura due to thrombocytopenia. 6-Widespread melanin pigmentation.6-Widespread melanin pigmentation. 7- Vit. B12 Neuropathy 7- Vit. B12 Neuropathy (subacute combined degeneration of the cord).(subacute combined degeneration of the cord). Affecting the sensory nerves and posterior & lateral columns. It is Affecting the sensory nerves and posterior & lateral columns. It is

symmetrical affecting the lower limbs more than the upper.symmetrical affecting the lower limbs more than the upper. Ataxia, Paresthesias, Hyporeflexia, Babinki & Clonus Ataxia, Paresthesias, Hyporeflexia, Babinki & Clonus

+.+.

Laboratory Findings:Laboratory Findings: 1- CBC: Macrocytic red cell indices, evaluates for 1- CBC: Macrocytic red cell indices, evaluates for

cytopenias.cytopenias. WBC and platelet may be moderately reduced.WBC and platelet may be moderately reduced. Reticulocyte count: is low in relation to the Reticulocyte count: is low in relation to the

degree of the anemia.degree of the anemia. 2- Bone marrow: 2- Bone marrow: Should be consider for any child with more than one Should be consider for any child with more than one

abnormal cell line on the CBC.abnormal cell line on the CBC. 3- Serum B12 level.3- Serum B12 level.

Treatment:Treatment: Initial dose: IM.Initial dose: IM.

10-50 mcg/d for 5-10 d, followed by 100-250 mcg/dose 10-50 mcg/d for 5-10 d, followed by 100-250 mcg/dose q2-4 wk.q2-4 wk.

OR.OR. 1mg/dose IM .1mg/dose IM .If there is evidence of neurological involvementIf there is evidence of neurological involvement

1mg/d IM for 2 wks.1mg/d IM for 2 wks.Maintenance :Maintenance : 1 mg IM monthly for life.1 mg IM monthly for life.

Folic Ac. Deficiency:Folic Ac. Deficiency: Requirement: 100 – 200 mic.g/d.Requirement: 100 – 200 mic.g/d. Sources: Greens vegetables, fruits, liver.Sources: Greens vegetables, fruits, liver. Absorptions: Small intestine.Absorptions: Small intestine. Functions: DNA synthesis, and a.a. Functions: DNA synthesis, and a.a.

interconversions.interconversions.

Causes of Folate Deficiency:Causes of Folate Deficiency: 1- Inadequate dietary intake:1- Inadequate dietary intake: 2- Inadequate absorption:2- Inadequate absorption: 3- Antifolate medications (e.g: Methiotraxate):3- Antifolate medications (e.g: Methiotraxate): 4- Medications that impair absorption (eg. Ant 4- Medications that impair absorption (eg. Ant

convulsions).convulsions). 5- Increased use ( eg, Chronic hemolysis such as 5- Increased use ( eg, Chronic hemolysis such as

SCA).SCA).

Clinical manifestations:Clinical manifestations: Onset 4-7 months of age the infant usually of low Onset 4-7 months of age the infant usually of low

birth wt. 0r significantly underweight ( marasmus, birth wt. 0r significantly underweight ( marasmus, or kwashiorkor ).or kwashiorkor ).

They present with:They present with: 1- Megaloblastic Anemia.1- Megaloblastic Anemia. 2- Irritability.2- Irritability. 3- Failure to gain wt.3- Failure to gain wt. 4-Chronic diarrhea.4-Chronic diarrhea. 5- Hemorrhage due to thrombocytopenia.5- Hemorrhage due to thrombocytopenia.

Laboratory Findings:Laboratory Findings: 1- CBC: Macrocytic red cell indices, evaluates for 1- CBC: Macrocytic red cell indices, evaluates for

cytopenias.cytopenias. WBC and platelet may be moderately reduced.WBC and platelet may be moderately reduced. Reticulocyte count: is low in relation to the Reticulocyte count: is low in relation to the

degree of the anemia.degree of the anemia. 2- Bone marrow: 2- Bone marrow: Should be consider for any child with more than one Should be consider for any child with more than one

abnormal cell line on the CBC.abnormal cell line on the CBC. Red blood cell folate level Red blood cell folate level (The best test for metabolically (The best test for metabolically

active folate).active folate). Serum Folate Serum Folate measures the circulating pool.measures the circulating pool.

Treatment:Treatment: Folic ac.Folic ac. 1-5 mg/d for 3-4 wks. Orally.1-5 mg/d for 3-4 wks. Orally.