Infancy & Childhood Diseases

8/8/2019 Infancy & Childhood Diseases

http://slidepdf.com/reader/full/infancy-childhood-diseases 1/48

DATE:22-04-2009



INFANCY AND CHILDHOOD DISEASE

INBORN ERRORS OF METABOLISM

SIR ARCHIBALD GARNOD COINED THE TERM INBORN

ERRORS OF METABOLISM IN 1908.

1.PHE NYL K ETONURIA

2.GALACTOSEMIA

3.CYSTIC FIBROSIS(MUCOVISCIDOSIS)



PHE NYL K ETONURIA

AUTOSOMAL R ECESSIVE DISOR DER

MOST COMMON- CLASSICAL PKU

BIOCHEMICAL ABNORMALITY

THER E IS SEVER E DEFICIE NCY OF PHE NYL ALA NINE

HYDROXYLASE WHICH LEADS TO HYPER PHE NYL

ALA NIN

EMI

A

INABILITYTO CONVER T PHE NYLALA NINE INTO TYROSINE



AT THE MOLECULAR LEVEL SEVER AL MUTA NT ALLELES OF

PHE NYL ALA NINE HYDROXYLASE GE NE HAVE BEE N

IDE NTIFIED WHICH ON MUTALION INDUCES A PAR TICULAR

ALTER ATION IN THE E NZYME.

AFFECTED INFA NTS AR E NORMAL AT BIR TH WITHIN A FEW

WEEKS IMPARME NT OF BR AIN DEVELOPME NT.

6 MONTHS

±

SE

VE

R E

ME NTAL

R ETA

R DAT

ION1/3 ---- NOT ABLE TO WORK

/3 ---- CA NNOT TALK

Seizures, Neurological abnormalities,pigmentation of hair & skin



Maternal Phenylketonuria

Treated patients during child bearing age

discontinue dietary treatement.

Child born-Mentally retarded,

Microcephalic,Congenital Heart disease

Prevention

Restriction of Phenylalanine intake early inlife.



Treatement

Dietary restriction ± Reduce or prevent

mental retardation.

Somatic gene therapy.



Autosomal recessive disorder of galactose

metabolism.

Lactose the major carbohydrate of milk is

Split into glucose and galactose in the

intestinal microvilli.





Biochemistry of galactose metabolism

Galactose+ATP-------------galactose1po4+ADP

Galactose1po4

+UDP glucose--------------UDPgalactose+

glucose1po4

UDPgalactose--------------UDP glucose

Common variant-Lack of galactose1PO4 uridyl

transferase



R are variant-lack of galactokinase

As a result of transferase lack accumulation of Galactose1po4 in liver,spleen,kidney,heart

Muscle,cerebral cortex and erythrocytes.

Alternative pathway is activated and

Accumulation of galactitol in tissue occurs.

Symptoms-vomiting and diarrhoea



Signs-

Hepatomegaly-Jaundice

Cataract

Mental retardation

Aminoaciduria

I nvestigation:

Demonstration of reducing sugar in urine

Deficiency of transferase in leucocytes and

and erythrocytes.

Antenatal diagnosis by assay of GALT

(Galactose1po4 uridyl transferase) activity

In cultured amniotic fluid cells.



T reatment

Dietary restriction

Even with dietary restriction older

patients are affected by speechdisorder and gonadal failure

(premature ovarian failure.)



C ystic fibrosis-(Mucoviscidosis)

It is an autosomal recessive widespread

disorder in epithelial transport affecting fluid

Secretion in Exocrine glands and the epithelial

lining of Respiratory,Gastrointestinal andreproductive tracts.

primary defect is due to abnormal function of

an epithelial chloride channel protein encodedby the cystic fibrosis transmembrane

conductance regulator gene on chromosome

Band 7q 31.2.



I ncidence:1 in 3200 live births in U.S.

1 IN 31000 live births in Africans

Abnormal viscid mucous secretions.

Non classical type:Disease is mild,growth less

Affected.survive to adolescence and adulthood.

Organs affected :Pancreas,Liver,Lungs,Salivary

glands and Reproductive system.



P ancreas:

I mpairs intestinal absorption-Leads to

Stunted growth and shorten survival.

Avitaminosis-A

Liver-Focal biliary cirrhosisHepatic nodularity.

Lungs-Bronchitis,Bronchiectasis,Lung abscess.

Salivary glands-Fibrosis.

Reproductive system-Azoospermia and

I nfertility in males.





C

l

i

n

i

ca

l

f

e

a

t

C linical features:

C hronic cough,sputum production,wheezing

Nasal polyp,Digital clubbing I ntestine-Meconium ileus

Rectal prolapse

Recurrent Pancreatitis,Protein calorieMamalnutrition,Hypo proteinemic edema

Salt loss syndromes-Acute salt depletion

C hronic metabolic acidosis





Investigation:Investigation:

Persistently elevated sweat electrolyte

Concentration

Sequencing the CFTR gene is the gold

standard

Gene therapy still in early stages

Life expectancy-30 Years



SIDS-Sudden infant death syndrrome

Defined as sudden death of an infant under 1 year of age which remains unexplained

After a through case investigation including

Performance of a complete autopsy,

Examination of death scene and review of the

Clinical history.

Infant usually dies in sleep.

Pseudonym-crib death or cot death.



TU MO URS

Heterotropia or C horistoma

Microscopically normal cells present in

abnormal

Location.pancreatic tissue found in wall of

Stomach or small intestine.Hamartoma

Execessive focal over growth of cells and tissues

Native to the or gan in which it occurs.BENIGNS TUMOURS

1.Haemangioma

2.Lymphangioma

3.Sacrococc eal teratoma



H emangioma

It is the most common tumour of infancy.

Types-Cavernous

Capillary-more cellular

Site-face and scalp

Morphology-flat to elevated red blue masses.

Referred as port wine stains.Course-Enlar ge or regress.

Von-Hippel Lindau Syndrome

Stur ge weber Syndrome





Lymphatic counterpart of Haemangioma

C haracterised by cystic and cavernous spaces

Lined by endothelioal cells and surrounded by

Lymphoid aggregatesThe spaces contain pale fluid

Site-Skin,deeper regions of neck,axilla,

mediastinum and retroperitonium.C ystic hygroma

Post nuchal collections of lymphatic fluid seen

in aborted foetuses with a 45x-Karyotype-Turner

Syndrome.



Most common germ cell tumour ofchildhood more than 40% of cases

Mechanism

Overlap of teratogenesis & onogenesis/

10%associated with congenital anamoly.

Associated with mid line defects-Menigocele

-Spinabifida.

75% Histologically mature with a benign course

12% Malignant,Lethal.





2 nd most common cause of death in the age group4-14yrs

I t is difficult to differentiate true tumours from tumour

like lesionsThe organs involved are Harmopoietic

system,neural tissue & soft tissues

Frequent demonstrations of a close relationshipbetween teratogenesis-abnormal development&

oncogenesis-tumour induction

Prevelence of genetic abnormalities that predispose

to cancer



85-90% of patients with cystic fibrosis areaffected

Pancreatic involvement is severe &impairs intestinal absorption leading to

stunted development & shorten survival

Mild: Accumulation of mucus in smallducts some dilatation of exocrine glands

Pancreatic AbnormalitiesPancreatic Abnormalities



Spontaneous regression or differentiation

Into mature elements.

Improved survival or cure of many childhoodMalignancies.0-4yrs 5-9yrs 10-14yrs

Leu emia Leu emia

etino lastoma etino lastoma

euro lastoma euro lastoma

Wilms tumour

epato lastoma epato carcinoma epato carcinoma

Soft tissue sarcoma Soft tissue sarcoma Soft tissue sarcoma

ha domyo sarcoma ings tumour steogenic sarcoma

eratomas Lymphoma hyroid carcinoma

S tumours S tumours odgkins disease



Primitive Histologic appearance of

many childhood tumours are referred

as small round blue cell tumours

Neuroblastoma

Lymphoma

Rhabdomyosarcoma

Ewings sarcoma



Most common solid tumour of childhood

15% of childhood cancer deaths

Origin-Neural crest

Site-Abdomen,Adrenal gland,

Paravertebral gland



Morphology

Microscopic nodules to masses that fill Abdomen

Cross section

Greyish,white,soft,friable,lar ge tumours.Microscopic

Cells which grow in solid sheets are roundTo ovoid,lar ge hyperchromatic nuclei

Surrounded by scanty cytoplasm

Homer wright pseudo rosettes formation



C linical features

<2 years-protuberant abdomen,fever,eight loss.

Older children-Remain unnoticed until

Metastasis causes hepatomegaly,ascitis And bonepain



RETI NOBLAST OMA

Most common malignant eye tumour of Childhood

Frequently occurs as a congenital tumour

Diagnosed before the age of 4 yearsSporadic-Non heritable,unifocal and

Unilateral

Familial-Bilateral,Multiple tumoursMorphology-Arise from a cell of neuro

Epithelial in origin in the posterior retina

Nodular masses with satellite seedlings



Microscopic -

Undiferrentiated areas-small round cells

ith lar ge hyperchromatic nuclei andScanty cytoplasm

Differentiated areas-Retinoblastomes,

Flexner wintersteiner rosettes.Metastasis-skull,distal bones,lymph node

Clinical features

Poor vision squinthitish hue to pupil(CATS EYE REFLEX)

Germ cell mutation-60-70%

Sporadic-30-40%



Familial type-increased risk of osteo

Sarcoma,soft tissue tumours

Treatment-Enucleation,Chemotherapy,Radiotherapy





WILMS TUMOUR

NephroblastomaMost common primary renal tumour in

Children

Age-2-5 yearsW AGR syndrome-Aniridia,genital and

Germ cell abnormalities,mental retardation

Denys drash syndrome-GonadalDysgenesis ->Nephropathy->renal failure

Both-loss of genetic material on

Chrosome 11p13





Morphology-Lar ge,solitary well

Circumscribed mass

Cut section-soft,homogenous,gray,cyst formation

Microscopic-blastemal,stromal,epithelial

cellTypes,sheets of small blue cells

Stromal cells are fibrotic or myxoid

Clinical features Abdominal mass,hematuria,pain

abdomen

Intestinal obstruction,hypertension



Prognosis-good

Treatment-Nephrectomy,chemo therapy

2 year survival rate 90% even for tumoursThat have spread beyond kidney

Survival for 2 years-implies cure



FETAL HYDROPS

Refers to accumulation of edema fluid inthe fetus during intra uterine growth

Fluid accumulation-progressive

Generalised-Hydrops fetalisLocalised-pleural,peritoneal effusion

Post nuchal-Cystic hygroma

CausesCVS,chrosomal-Turner syndrome,

Trisomy-18,21

Fetal anaemia-immune hydrops



Infection-CMV,syphilis,Toxoplasmosis

Tumours,Metabolic disorders

IMMUNE HYDROPS

Defined as hemolitic disease in the new

Born caused by blood group incompatibilityBetween mother and child

Fetus inherits red cell antigenic

Determinants from father and a maternalImmune reaction occurs->hemolytic disease

In the infant

Major antigens-ABO,Rh antigens

Etil d th i



Etilogy and pathogenesis

D antigens ± major cause of Rh

IncompatibilityMorphology

Bone marrow-Compensatory hyperplasia

0f erythroid precursorsPresence of lar ge number of immature red

Cells,reticulocytes,normoblasts,

Erythroblasts-Erythroblastosis fetalisClinical features

Pallor,Hepatosplenomegaly,Jaundice,

Generalised edema,neurology involment

Tohelp protectyour privacy, PowerPointprevented thisexternalpicturefrom being automatically downloaded.To download and display thispicture,click Optionsin the MessageBar, and then click Enableexternalcontent.



I i i



Investigations

Amniocentesis,Chorionic villus examination

Fetal blood samplingPrevention-RhIg(antiDAbs0 given at

28 weeks and within 72 hrs of delivery to

Rh-ve mother Tretment-Photo therapy,Total exange

Transfusion,administration of high dose

Of Ig.

Tohelp protectyour privacy, PowerPointprevented thisexternalpicturefrom being automatically downloaded.To download and display thispicture,click Optionsin the MessageBar, and then click Enableexternalcontent.



Pictures

Hydrops fetalis



Documents

Infancy & Childhood Diseases