infancy & childhood diseases
TRANSCRIPT
8/8/2019 Infancy & Childhood Diseases
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DATE:22-04-2009
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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)
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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
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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
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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.
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Treatement
Dietary restriction ± Reduce or prevent
mental retardation.
Somatic gene therapy.
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Autosomal recessive disorder of galactose
metabolism.
Lactose the major carbohydrate of milk is
Split into glucose and galactose in the
intestinal microvilli.
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Biochemistry of galactose metabolism
Galactose+ATP-------------galactose1po4+ADP
Galactose1po4
+UDP glucose--------------UDPgalactose+
glucose1po4
UDPgalactose--------------UDP glucose
Common variant-Lack of galactose1PO4 uridyl
transferase
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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
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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.
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T reatment
Dietary restriction
Even with dietary restriction older
patients are affected by speechdisorder and gonadal failure
(premature ovarian failure.)
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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.
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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.
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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.
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C
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ca
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f
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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
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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
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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.
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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
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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
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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.
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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.
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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
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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
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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
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Primitive Histologic appearance of
many childhood tumours are referred
as small round blue cell tumours
Neuroblastoma
Lymphoma
Rhabdomyosarcoma
Ewings sarcoma
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Most common solid tumour of childhood
15% of childhood cancer deaths
Origin-Neural crest
Site-Abdomen,Adrenal gland,
Paravertebral gland
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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
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C linical features
<2 years-protuberant abdomen,fever,eight loss.
Older children-Remain unnoticed until
Metastasis causes hepatomegaly,ascitis And bonepain
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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
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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%
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Familial type-increased risk of osteo
Sarcoma,soft tissue tumours
Treatment-Enucleation,Chemotherapy,Radiotherapy
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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
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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
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Prognosis-good
Treatment-Nephrectomy,chemo therapy
2 year survival rate 90% even for tumoursThat have spread beyond kidney
Survival for 2 years-implies cure
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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
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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
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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
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I i i
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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.
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Pictures
Hydrops fetalis
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