– Congential aortic stenosis
– Anomalous origin of coronary artery from pulmonary artery
SIDS (Differential diagnosis)
• Genetic/Metabolic Defects
– Long QT syndrome (SCNSA + KCNQ1 mutations)(Sodium and potassium channel abnormalities.) 1%
– Fatty acid oxidation disorders (MCAD, LCHAD, SCHAD mutations) 5%
– Histiocytoid cardiomyopathy (MTCYβ mutations)
– Abnormal inflammatory responsiveness
(Partial deletion of C4a and C4b)
After how many weeks does the female amniotic fluid become bacteriocidal
Fetal and Perinatal Infections - Pathways
• Ascending from the vagina and cervix.
• Hematogenous dissemination from the placenta.
• Maternal to fetal transfusion at delivery(Hepatitis B and HIV)
• Direct contact at birth.
• From the environment post-partum.
• Accidental introduction at the time of
procedures - amniocentesis.
Fetus acquires infection by
– Inhalation of infected amniotic fluid
– Passage through birth canal
• Fetal birth infections
Infections Acquired by the Hematogenous Route
• Congenital syphilis.
• Parvovirus B19.
• Human Immunodeficiency Virus(HIV).
• Other infections(Listeria, parasitic infections).
O= OTHER INTRAUTERINE INFECTIONS
Listeria monocytogenes (late-onset sepsis)
• Hematogenous through the placenta.
• Herpes simplex infection is an exception to this as most infections are due to:
– Direct contact at the time of delivery.
– Ascending infection.
Hepatomegaly with jaundice
Bony changes resembling osteomyelitis
Eye and heart Manifestations
• Ocular lesions:
– Corneal changes.
• Cardiac lesions:
– Patent ductus arteriosus.
– Septal defects.
An autosomal recessive systemic disorder of exocrine glands characterized by
– Chronic pulmonary disease
– Deficient exocrine pancreatic function
– Other complications of inspissated mucus in a number of organs, including the small intestine, liver and the reproductive tract.
Cystic fibrosis pathogenesis
• Gene on chromosome 7 (7q31.2) encodes for a protein called the CF transmembrane conductance regulator (= CFTR).
• Phosphorylation of CFTR by protein kinase A using cAMP controls the chloride channel in the apical membranes of eccrine glands.
Types of Mutations in cystic fibrosis
In 70 % cases – 3 base pair deletion that results in loss of a phenylalanine residue at amino acid position 508(∆F508).
• The remaining patients exhibit multiple (more than 800) different mutations.
Plugging of submucosal tracheobronchial mucous glands and ducts.
• Obstruction of bronchioles with mucus, associated with marked hyperplasia and hypertrophy of the mucus-secreting cells.
LUng infections from CF
– Chronic bronchitis.
– Lung abscesses.
• In this organ, there is the same mucous obstruction of ducts accompanied by:
– Secondary dilatation and cystic changes of the distal ducts and atrophy of secretory cells.
– Destruction of parenchyma.
• These effects result in chronic pancreatitis in 85% of patients with CF.
• Discovered between age of 2-12 months.
• Child presents with symptoms of malabsorption secondary to pancreatic insufficiency:
– Foul-smelling steatorrhea.
– Malnutrition • Edema
– Failure to thrive.
• Two clinical clues in children:
– Nasal polyps
– Rectal prolapse
• Pilocarpine sweat test
– Normal sweat: chloride = 10 mEq/L.
– CF sweat, severe variant: chloride >60 mEq/L.
– CF sweat, mild variant: chloride = 40-60 mEq/L
• Genetic diagnosis
• Autosomal recessive disorder characterized by
– Progressive mental retardation caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase.
• Point mutation in the PAH gene on 12q.
• Deficiency of Phenylalanine Hydroxylase (PAH) results in
– Formation of Phenylketones
• Hyperphenylalaninemia causes irreversible brain damage
– Complete interference with amino acid transport system in brain
– Inhibiting the synthesis of neurotransmitters
PKU clinical features
• Affected infant is normal at birth
• Mental retardation develops within few months
• Tend to have fair skin, blond hair and blue eyes.
• Mousy odour
An autosomal recessive deficiency of Galactose -1-phosphate uridyl transferase, the enzyme that catalyzes the conversion of galactose to glucose.
Infants fed milk rapidly develop hepatosplenomegaly, jaundice and hypoglycemia.
• Cataracts and Mental retardation.
• M/E –
extensive and uniform fat
accumulation in liver and marked bile ductal proliferation, cholestasis and fibrosis.
• Autosomal recessive disease characterized by chronic or intermittent jaundice and accompanied by a „black‟ liver.
• Defective transport of conjugated bilirubin from hepatocytes to canalicular lumen
• Associated defect in hepatic excretion of
accumulation of coarse, iron free, dark brown granules in hepatocytes and Kupffer cells.
pigment is located in lysosomes and it appears to be composed of polymers of epinephrine metabolites, not bilirubin pigment
• Familial conjugated Hyperbilirubinemia
defect in the excretion of conjugated bilirubin into the biliary canaliculi with the bilirubin being absorbed into the blood.
jaundice, attacks of intermittent epigastric discomfort and occasionally abdominal pain, and fever.