CONGENITAL DISEASES

• the transformation of the simple three germ layers into distinct organs

  Organogenesis
• Tissues combine to form organ during 8th week to birth

  Gastrulation
• 3 GERM LAYERS formed from Gastrulation

  • ECTODERM: outermost layer • MESODERM: middle layer • ENDODERM: innermost layer
• a band called the primitive streak appears along the back of the embryo during week 3. Followed by the connective tissue progenitor cells, notochord, neural tube, heart, central nervous system, arms, legs and other organ rudiments. 

• By week _ , all the organs that will be present in the newborn have begun to develop

  week 8
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  • First 2 weeks after conception: GERMINAL STAGE

  • 3 rd Week to 8th Week: EMBRYONIC PERIOD

  • 9 th Week to 37th Week:FETAL PERIOD

  • FIRST MONTH ( 4 WEEKS) AFTER BIRTH: NEONATAL PERIOD
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  By week 12, sucks thumb, kicks, makes fists and faces, and has the beginnings of teeth (UNDER THE GUMS)

  • Fingernails and toenails begin to develop and the external ears are also formed
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  Vocal cords will be formed by 18 weeks
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  By the end of the second trimester, the woman feels distinct kicks and jabs and may detect fetal hiccup.
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  In the final trimester, fetal brain cells link into networks as organs elaborate and grow, and fat fills out the skin.
• The digestive and respiratory systems mature last.

• WEEK 16

  • 2 ND TRIMESTER

  • Muscle tissue and bone continue to form

  • Skin begins to form

  • Meconium develops in the baby's intestinal tract o MECONIUM: baby's first bowel movement.

  • sucking motions (sucking reflex)

  • length : 4 to 5 inches • weighs : 3 ounces.
• Sex organs become more distinct by week 6

• Time when genetic abnormalities, toxic substances, or viruses can alter a specific structure is critical period

• • Most birth defects develop during the embryonic period

  • More severe than those that arise during the fetal period
• Newborn Screening A procedure to detect if a newborn has congenital metabolic disorders that may lead to mental retardation or death Part of “Unang Yakap”: Early Essential Newborn care Protocol
• Procedure of New born screening:

  • Testing is done on the 24 to 48 hours after birth.

  • heel prick method

  • Blood drops on NBS kit

  • Air dry for 4 hours

  • Send to testing facility

  • Blood Collector: Doctor, Nurse, Midwife, Medical technologist
• Newborn Screening Disorders Basic (6 disorders)

  1. Congenital hypothyroidism (CH)
  2. Congenital adrenal hyperplasia (CAH)
  3. Phenylketonuria (PKU)
  4. Galactosemia (GAL)
  5. Glucose 6 phosphate deficiency (G6PD)
  6. Maple syrup urine disease (MSUD): added in 2012
• EXPANDED NEWBORNS (28 disorders): Current 6 disorders plus 22 more disorders such as hemoglobinopathies and additional metabolic disorders, namely, organic acid, fatty acid oxidation, and amino acid disorders.
• 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
• 2 TYPES OF CH

  1.• 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

  2. • Thyroid dyshormonogenesis • Dual oxidase 2 (DUOX2) – 15 • Solute Carrier Family 5 Member (SLC5A5) – 19 • Thyroglobulin (TG) – 8 • thyroid peroxidase (TPO) – 2
• MANIFESTATION OF CH

  • Early manifestations

  • Prolonged jaundice

  • Inactive defecation

  • Umbilical Hernia

  •Hypotonia

  • Skin: rough and dry

  • Delayed overall development

  Late manifestations:

  • Mental retardation

  • Growth retardation

  • Delayed skeletal maturation

  • Delayed dental development and tooth eruption

  • Delayed puberty
• Treatment ON CH L-thyroxine tablet: provides more thyroid hormone
• 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

  
  

  1. Salt-wasting: Classic form: 1 in 15,000 newborns - 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
• Manifestations of Congenital Adrenal Hyperplasia

  • 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 Manifestations

  • Precocious puberty: child's body begins changing into that of an adult (puberty) too soon

  • “Skin Puberty”: pubic hair growth, oily skin, “body odor"

  • Dark skin color

  • Short adult stature

  Treatment : Hormone replacement Surgery
• Phenylketonuria


  Genetic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene
• 1 in 10,000 to 15,000 newborns have phenylketonuria
• Phenylketonuria

  • Autosomal recessive
  • Mutation in phenylalanine hydroxylase (PAH) gene – chromosome 12 missing or lack of phenylalanine hydroxylase
  • Phenylalanine is neurotoxic
• The first effects of phenylketonuria are usually seen around 6 months of age
• Manifestations of phenylketonuria

  • Vomiting
  • Hyperactivity
  • Seizures and hypertonia
  • Musty or mousy urine odor
  • Light hair and skin color
  • Seborrheic or eczematoid rash
  • Mental retardation
• Treatment for phenylketonuria

  1. Complete avoidance of food containing high amounts of phenylalanine

  2. Calculated intake of low protein/phenylalanine natural food

  3. Sufficient intake of fats and carbohydrates
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  1. Galactose-1-phosphate uridyltransferase (GALT)

  • Chromosome 9
  • Classic Galactosemia
  • Type I Galactosemia

  2. Galactokinase 1 (GALK1)

  • Chromosome 17
  • Type II Galactosemia

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

  • Chromosome 1
  • Type III
• GALACTOSEMIA

  • disorder that affects how the body processes Galactose
  • Component of dietary sugars
  • Converted to GLUCOSE for energy storage (glycogen) and energy production
  • autosomal recessive
• MANIFESTATION

  Develop a few days to two weeks after initiation of milk feedings

  Poor suck, Vomiting, occasionally diarrhea, Jaundice Lethargy, weakness, coma, Septicemia (E. coli)

  Late due to galactose deposits in tissues Liver: hepatomegaly, edema, ascites, cirrhosis Lens: cataracts Brain: mental retardation Kidney Growth failure

  TREATMENT: eliminate lactose and galactose from diet
• G6PD deficiency

  • Glucose-6 Phosphate Dehydrogenase (G6PD gene)

  • X chromosome (Xq28) - provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase

  • X-linked recessive

  • 400 million people worldwide

  • Hemolytic anemia: due to RBC hemolysis, exposed to oxidative stress
• Glucose-6-phosphate dehydrogenase

  - protect red blood cells from damage and premature destruction

  - prevent Hemolysis (destruction of red blood cells)

  • responsible for the first step in the Pentose phosphate pathway Pentose phosphate pathway: convert glucose to ribose-5-phosphate
• Triggering factors of G6PD

  • Illness such as viral or bacterial

  • Anti-pyretics or analgesics like aspirin

  • Some antibiotics • Some antimalarial drugs

  • Soya food

  • Red wine

  • Legumes (monggo, gabanzos, abitsuelas)

  • Napthalene balls

  • Fava beans

  • Blueberries

  MANIFESTATION

  • Pallor

  • Extreme tiredness

  • Rapid heartbeat

  • Rapid breathing

  • Jaundice

  • Splenomegaly

  • Tea-colored urine

  TREATMENT

  • Avoid triggers

  • Phototherapy

  • Blood transfusion