Week 13-14 Cyto

• Organogenesis


  Transformation of the simple three germ layers into distinct organs
• Germ layers

  Ectoderm (outermost layer), Mesoderm (middle layer), Endoderm (innermost layer)
• Embryonic development


  1. Primitive streak appears (week 3)

  2. Connective tissue progenitor cells, notochord, neural tube, heart, central nervous system, arms, legs and other organ rudiments form

  3. All organs that will be present in the newborn have begun to develop (by week 8)
• Stages of development

  • Germinal stage (first 2 weeks after conception)
  • Embryonic period (3rd week to 8th week)
  • Fetal period (9th week to 37th week)
  • Neonatal period (first month after birth)
• Fetal development

  1. Body proportions approach those of a newborn

  2. Bone replaces softer cartilage

  3. Nerve and muscle functions become coordinated

  4. Sex organs become more distinct (by week 6)

  5. Sucks thumb, kicks, makes fists and faces, and has the beginnings of teeth (by week 12)

  6. Fingernails and toenails begin to develop and the external ears are also formed

  7. Vocal cords will be formed (by 18 weeks)

  8. Distinct kicks and jabs felt, fetal hiccup detected (by end of second trimester)

  9. Fetal brain cells link into networks as organs elaborate and grow, and fat fills out the skin (in final trimester)

  10. Digestive and respiratory systems mature last
• Week 16


  • Muscle tissue and bone continue to form
  • Skin begins to form
  • Meconium develops in the baby's intestinal tract
  • Sucking motions (sucking reflex)
  • Length: 4 to 5 inches
  • Weight: 3 ounces
• Gastrulation


  Process during embryonic development that changes the embryo from the blastula (single layer of cells) to the gastrula (multiple layers of cells)
• Birth defects can be minor or severe
• Critical period


  Time when genetic abnormalities, toxic substances, or viruses can alter a specific structure
• Most birth defects develop during the embryonic period and are more severe than those that arise during the fetal period
• Some birth defects can be attributed to an abnormal gene
• Newborn screening


  Procedure to detect if a newborn has congenital metabolic disorders that may lead to mental retardation or death
• Newborn screening is part of the "Unang Yakap": Early Essential Newborn care Protocol

  
• Importance of newborn screening

  Most newborns with metabolic disorders look normal at birth, but can be reversed or treated to prevent mental retardation or death
• Newborn screening procedure

  1. Testing is done 24 to 48 hours after birth using the heel prick method

  2. Blood drops on NBS kit

  3. Air dry for 4 hours

  4. Send to testing facility

  5. Blood collector: Doctor, Nurse, Midwife, Medical technologist
• Newborn screening is covered by law and is mandatory for every child
• Basic newborn screening disorders (6 disorders)

  • Congenital hypothyroidism (CH)
  • Congenital adrenal hyperplasia (CAH)
  • Phenylketonuria (PKU)
  • Galactosemia (GAL)
  • Glucose 6 phosphate deficiency (G6PD)
  • Maple syrup urine disease (MSUD)
• Expanded newborn screening disorders (28 disorders)


  • Basic 6 disorders plus 22 more disorders such as hemoglobinopathies and additional metabolic disorders (organic acid, fatty acid oxidation, amino acid disorders)
• Congenital hypothyroidism (CH)


  Caused by thyroid gland failing to develop or function properly, leading to shortage of thyroid hormones which are important for normal brain development, muscle and bone development, regulation of body temperature, and maintaining heart rate
• Manifestations of congenital hypothyroidism

  • Early: Prolonged jaundice, inactive defecation, umbilical hernia, hypotonia, rough and dry skin, delayed overall development
  • Late: Mental retardation, growth retardation, delayed skeletal maturation, delayed dental development and tooth eruption, delayed puberty
• Treatment for congenital hypothyroidism - L-thyroxine tablet to provide more thyroid hormone
• Congenital adrenal hyperplasia (CAH)

  Autosomal recessive disorder caused by mutations in the CYP21A2 gene, leading to excess production of male sex hormones (androgens)
• Types of 21-hydroxylase deficiency in CAH

  • Classic form: Salt-wasting (most severe), Simple virilizing
  • Non-classic / late onset
• Manifestations of congenital adrenal hyperplasia

  • Early: Increased pigmentation, ambiguous genitalia in female infants, poor suck, weak cry, vomiting, excessive urination, dehydration, irritability and seizures, failure to thrive, hypotension, shock, coma
  • Late: Precocious puberty, "skin puberty", dark skin color, short adult stature
• Galactosemia


  Disorder that affects how the body processes galactose, a component of dietary sugars Converted to GLUCOSE for energy storage (glycogen) and energy production

  • autosomal recessive
• Manifestations of galactosemia

  • Develop a few days to two weeks after initiation of milk feedings: Poor suck, vomiting, jaundice, lethargy, weakness, coma, septicemia (E. coli)
  • Late: Liver problems, cataracts, mental retardation, kidney problems, growth failure
• Thyroid dysgenesis: thyroid gland fails to develop or function properly

  2 Genes involved

  • Paired box gene 8 (PAX8) in chromosome 15

  • Thyroid stimulating hormone receptor (TSHR) in chromosome 14
• Thyroid dyshormonogenesis - condition in the synthesis of hormones in the thyroid

  • Dual oxidase 2 (DUOX2) – 15

  • Solute Carrier Family 5 Member (SLC5A5) – 19

  • Thyroglobulin (TG) – 8

  • thyroid peroxidase (TPO) – 2
• Thyroid Gland: butterfly shaped organ that produces thyroid hormones

  • makes iodine-containing hormones

  FUNCTIONS

  • Normal brain development
  • Development of muscles and bones
  • Regulation of body temperature
  • Maintain heart rate
• Free thyroid hormone (FT4): determines whether the thyroid is performing properly
• Congenital Hypothyroidism

  • 1 in 2,000 to 4,000 newborns

  • Autosomal recessive

  • 15 to 20 % of cases

  • Most common – shortage of iodine in the diet of the mother during pregnancy
• Adrenal Gland: located on top of the kidneys

  Hormones produced in Adrenal Gland

  1. Epinephrine or adrenalin: for vigorous physical activities
  2. Cortisol: maintains blood sugar levels, protects the body from stress, and suppress inflammation
  3. Aldosterone (salt-retaining hormone): regulates the amount of salt retained by the kidneys.
• CONGENITAL ADRENAL HYPERPLASIA

  • Autosomal recessive

  • 21-hydroxylase deficiency : produce excess androgens (MALE SEX HORMONES)

  • Mutations in the Cytochrome P450 Family 21 Subfamily A Member 2 (CYP21A2 gene)

  found in Chromosome 6 within the human leukocyte antigen histocompatibility (HLA) complex.
• CYP21A2 gene: provides instructions for making an enzyme called 21-hydroxylase
• 3 types of 21-hydroxylase deficiency

  • Classic form: 1 in 15,000 newborns

  1.Salt-wasting: Most severe

  CYP21A2 mutations that result in a completely non-functional enzyme

  2. Simple virilizing

  CYP21A2 gene mutations that allow the production of low levels of functional enzyme

  3. Non-classic / late onset: 1 in 1,000 individuals

  CYP21A2 mutations that result in the production of reduced amounts of the enzyme

  • More enzyme produced compared to the other types
• Treatment for CAH

  • Hormone replacement

  • Surgery
• TREATMENT for Galactosemia: eliminate lactose and galactose from diet
• MUTATIONS IN GALACTOSEMIA

  1. Galactose-1-phosphate uridyltransferase (GALT)

  • Chromosome 9
  • Classic Galactosemia
  • Type I Galactosemia
  • Most Severe
  • 1 in 30,000 to 60,000

  2. Galactokinase 1 (GALK1)

  • Chromosome 17
  • Galactokinase deficiency
  • Type II Galactosemia
  • 1 in 100,000

  3. UDP-Galactose-4-epimerase (GALE)

  • Chromosome 1
  • Galactose epimerase deficiency
  • Type III
  • Very rare
  • Symptoms vary from mild to severe
• Meconium

  • baby's first bowel movement
• Enactment of the Newborn Screening Act of 2004

  • April 6, 2004