IEM and Cystic Fibrosis (10) Flashcards
What are Inborn Errors of Metabolism (IEM)?
Rare GENETIC defects in metabolism
How are IEM usually inherited?
Autosomal Recessive or X-linked
What is the most important way to make a diagnosis of an IEM?
High index of suscpicion
In any critically ill neonate that was born healthy that quickly deteriorates, what should you consider?
IEM
Does a Negative newborn screening for IEMs exclude the diagnosis?
NO
List some overall physical findings with IEM disorders
Dysmorphic features - abnormal hair
Abnormal odors
Poor feeding, jaundice
EYE issues
What are 3 common IEMs?
- Phenylketonuria
- Galactosemia
- Cystic Fibrosis
What population is PKU (phenylketonuria) more common?
Scandinavian and caucasian descent
What enzyme(s) are deficient with PKU?
- Phenylalanine Hydroxylase
2. Dihydropteridine Reductase (less common)
With PKU what enzyme is deficient and what reaction does not take place?
Phenylalanine Hydroxylase
- Phenylalanine is NOT converted to Tyrosine
How is PKU inherited?
Autosomal Recessive
What are the main findings with PKU?
LOW IQ
Musty odor
Decreased pigmentation of skin and hair
Can’t talk or walk in severe cases
Low IQ, musty odor and decreased pigmentation of skin and hair is seen with what disease?
Phenylketonuria (PKU)
What enzyme is deficient with Galactosemia?
GALT (galactose-1 phosphate uridyl Transferase)
How is Galactosemia inherited?
Autosomal Recessive
What organ systems are normally affected by Galactosemia?
Liver
Eyes
Brain
What is deposited (increased) in tissues with galactosemia?
Galactose-1 phosphate
With Galactosemia, a few hours after ___ ingestion vomiting and diarrhea present
Milk ingestion
Galactosemia deposits Galactose-1 phosphate in the liver, eyes and brain. Describe what happens to those organs.
Liver - hepatomegaly
Eyes - cataracts
Brain - decreased IQ
Hepatomegaly, Cataracts and intellectual deficits are linked with what IEM?
Galactosemia
Another name for Cystic Fibrosis?
Mucoviscidosis
What is the primary population that suffers from cystic fibrosis?
CAUCASIANS
Approximately how frequent do caucasians suffer from cystic fibrosis?
1/20 are carriers
1/2500 live births
How is Cystic Fibrosis inherited?
Autosomal Recessive
What is Cystic Fibrosis?
Disorder of ion transport that results in abnormally viscous secretions in the respiratory, GI and reproductive systems
What systems are mainly affected with Cystic Fibrosis?
Respiratory
GI
Reproductive
Specifically, what ions is transport disrupted with Cystic Fibrosis?
Cl-
HCO3-
What gene is mutated with Cystic Fibrosis?
CFTR
On what chromosome is the CFTR gene?
7q31.2
Where is the most common site for CFTR mutations to take place?
Protein misfolding in the ER and Golgi so it never makes it to the cell membrane
Describe the setup of the CFTR channel
1 R domain
2 Nucleotide binding sites
2 transmembrane domains
How is Cl- pumped out of the CFTR channel?
- Agonist (ex. Ach) activates cAMP
- cAMP activates protein kinase A
- Protein Kinase A phosphorylates the CFTR channel using ATP and it opens
= Cl- is let out
In all tissues besides the sweat glands, what does the CFTR gene inhibit?
Enac
- epithelial sodium channel
When the CFTR gene is working normally, describe the sweat glands
The CFTR channel allows Cl- to be reabsorbed from the sweat and the EnaC channel allows Na+ to be reabsorbed from the sweat as well.
= Water follows sodium == hypotonic sweat!
When the CFTR gene is not working normally, describe the sweat glands
The CFTR channel does NOT allow Cl- to be reabsorbed from the sweat and so the EnaC channel follows and does NOT allow Na+ to be reabsorbed.
= Water follows sodium == Hypertonic sweat!
VERY SALTY SWEAT
If a mother thinks her child has salty sweat, what could that indicate?
Cystic Fibrosis
With Cystic fibrosis, sweat glands are morphologically ______
UNaffected
In what organ does cystic fibrosis affect bicarbonate transport?
Pancreas
Cystic Fibrosis leads to pancreatic insufficiency how?
Decreased bicarbonate secretions
= acidic secretions with low pH
With Cystic Fibrosis, the pancreas is secreting acidic material. What does this result in?
Plugged ducts that accumulate bacteria
Plugged pancreatic ducts that accumulate bacteria ultimately leads to?
Decreased fat absorption and decreased Vitamin A!
Describe a normally functioning CFTR gene in the airways
- CFTR channel allows Cl- to leave the cell and enter the airway
- Na+ and water are reabsorbed into the cell
= Normal mucus created
Describe a mutated CFTR gene in the airways
- CFTR channel does NOT allow Cl- to leave the cell
- TONS of Na+ and water are reabsorbed into the cell
= DEHYDRATED AND THICK MUCUS created
When dehydrated mucus is created in the airways, what are the effects?
Decreased mucociliary movements and increased obstruction and pulmonary infections
The presence of ______ in the lungs is very common due to the thick secretions in the lungs
Pulmonary infections!!
Meconium Ileus
Thick viscous plugs in small intestines
- seen with Cystic Fibrosis
Liver alterations in cystic fibrosis?
Steatosis, cirrhosis and obstruction of bile ducts
When do liver alterations with cystic fibrosis present in life?
Usually later, after puberty
- steatosis, cirrhosis, bile duct obstructions
What is the most common cause of death with cystic fibrosis?
Pulmonary infections and changes
Thick mucus in the lungs leads to?
- Obstruction
2. Infection
Describe the bronchiole changes seen with cystic fibrosis
Distended with hypertrophy and hyperplasia of the mucus-secreting cells
4 organisms that cause pulmonary infections in cystic fibrosis patients?
- Staph Aureus
- Haemophilus Influenzae
- Pseudomonas Aeruginosa
- B. Cenocepacia
4 organisms that cause pulmonary infections in cystic fibrosis patients?
- Staph Aureus
- Haemophilus Influenzae
- Pseudomonas Aeruginosa
- B. Cenocepacia
What is the worst organism that causes the highest mortality rate with cystic fibrosis pulmonary infections?
B. Cenocepacia
What is occasionally present in the noses of cystic fibrosis patients?
Nasal polyps
How does Cystic Fibrosis affect the reproductive system?
In males: azoospermia and infertility
* Bilateral absence of vas deferens *
With the male reproductive system, what is normally absent with cystic fibrosis?
Vas deferens
With what pulmonary infection organism, do the lungs appear green with?
Pseudomonas Aeruginosa
Define SIDS
Sudden Infant Death of a less than 1 year old that cannot be explained after reviewing autopsy, death scene and history
Define SUID
Sudden Unexpected Infant Death due to an anatomic or biochemical finding on autopsy
Is SIDS = SUID?
NO
What is the leading cause of infant death between 1 month and 1 year of age?
SIDS
When is the peak time for SIDS deaths to occur?
Between 2 and 4 months of age
What 3 factors can contribute to SIDS
- Vulnerable infant
- In a critical developmental period
- Exogenous stressor
What populations are more susceptible to SIDS?
Black and American Indian
It is believed that a vulnerable infant has issues with arousal and respiratory control. What system controls that?
Serotonin
What is the most common physical exam finding with SIDS?
Petechiae on lungs, thymus, heart
Maternal ____ is associated with a higher chance of SIDS
Smoking
What is the order of a hypothesis to how SIDS results?
- respiratory infection
- decreased activity of laryngeal chemoreceptors
- increased mucus production
- child sleeps prone
3 risk factors for SIDS?
- Vulnerable infant
- In critical developmental period
- Exogenous stressor
