CONGENITAL METABOLIC DISORDERS

• congenital hypothyroidism


  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
• 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
• 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
• Thyroid dysgenesis


  thyroid gland fails to develop or function properly
• Paired box gene 8 (PAX8) in chromosome 15 and Thyroid stimulating hormone receptor (TSHR) in chromosome 14


  two genes involved in thyroid dysgenesis
• thyroid dyshormonogenesis


  - Dual oxidase 2 (DUOX2) - 15

  - Solute Carrier Family 5 Member (SLC5A5) - 19

  - Thyroglobulin (TG) - 8

  - thyroid peroxidase (TPO) - 2
• L-thyroxine tablet


  treatment for congenital hypothyroidism that provides more thyroid hormone
• congenital adrenal hyperplasia


  Manifestations

  - 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
• 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
• salt-wasting


  - most severe

  - CYP21A2 mutations that result in a completely non-functional enzyme
• simple virilizing


  CYP21A2 gene mutations that allow the production of low levels of functional enzyme
• non-classic or late onset


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

  - More enzyme produced compared to the other types
• adrenal gland


  Located on top of the kidneys

  Regulate electrolytes

  Secretes hormones associated with stress response (adrenalin and norepinephrin)
• Epinephrine (adrenaline)


  for vigorous physical activities
• cortisol


  maintains blood sugar levels, protects the body from stress, and suppress

  inflammation
• aldosterone


  salt-retaining hormone : regulates the amount of salt retained by the

  kidneys.
• congenital adrenal hyperplasia


  hormone replacement and surgery are treatment for?
• Phenylketonuria


  - missing or lack of phenylalanine hydroxylase

  - The first effects are usually seen around 6 months of age

  - Delayed development

  - Will lead to mental retardation

  
  

  MANIFESTATION

  - Vomiting

  - Hyperactivity

  - Seizures and hypertonia

  - Musty or mousy urine odor

  - Light hair and skin color

  - Seborrheic or eczematoid rash

  - Mental retardation
• Phenylketonuria


  - Complete avoidance of food containing high amounts of phenylalanine

  - Calculated intake of low protein/phenylalanine natural food

  - Sufficient intake of fats and carbohydrates

  
  

  The following are treatments for?
• phenylalanine hydroxylase (PAH) gene - chromosome 12


  In phenylketonuria, mutation occurs in?
• Galactosemia


  - disorder that affects how the body processes Galactose

  - Component of dietary sugars

  - Converted to GLUCOSE for energy storage (glycogen) and energy production
• Galactosemia


  MANIFESTATION

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

  - Poor suckVomiting, 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
• Galactosemia


  eliminate lactose and galactose from diet is treatment for?
• GALT, GALK1, GALE


  In galactosemia, mutation occurs in?
• Galactose-1-phosphate uridyltransferase


  - Chromosome 9

  - Classic Galactosemia

  - Type I Galactosemia
• Galactokinase 1


  - Chromosome 17

  - Type II Galactosemia
• UDP-Galactose-4-epimerase


  - Chromosome 1

  - Type III
• Type I Galactosemia


  - Classic galactosemia

  - Most common

  - Most severe

  - 1 in 30,000 to 60,000 newborns
• Type II Galactosemia


  - Galactokinase deficiency

  - 1 in 100,000
• Type III Galactosemia


  - Galactose epimerase deficiency

  - Very rare

  - Symptoms vary from mild to severe