Diseases of Infancy and Childhood: Inborn Errors of Metabolism and SIDS

Question 1

what are inborn errors of metabolism?

Answer 1

a large group of rare genetic diseases that generally result from a defect in an enzyme or transport protein which results in a block in a metabolic pathway

Question 2

most inborn errors of metabolism are rare diseases that are generally inherited as what?

Answer 2

inherited as autosomal recessive or x-linked traits

Question 3

What is considered most important when making a diagnosis of an inborn error of metabolism?

Answer 3

a high index of suspicion is most important in making the diagnosis

Question 4

what are the different categories of inborn errors of metabolism?

Answer 4

disorders that result in toxic accumulation; or disorders of energy production/utilization

Question 5

what are disorders that result in toxic accumulation?

Answer 5

disorders of protein metabolism or disorders of carbohydrate intolerance; lysosomal storage disorders

Question 6

what are disorders of energy production, utilization?

Answer 6

fatty acid oxidation defects; disorders of carbohydrate utilization, production; mitochondrial disorders; peroxisomal disorders

Question 7

what are the goals of treatment for patients with IEMs?

Answer 7

prevention of further accumulation of harmful substances, correction of metabolic abnormalities, and elimination of toxic metabolites

Question 8

frequently, what is the most important clue for diagnosing IEMs?

Answer 8

the most important clue is a history of deterioration, often-life threatening, after an initial period of apparent good health ranging from hours to weeks, usually following an uncomplicated pregnancy

Question 9

what could be the diagnosis of term infants with the risk for sepsis who develop the symptoms of sepsis?

Answer 9

metabolic disease may be nearly as common as sepsis; a negative newborn screen result does not exclude the diagnosis of metabolic disease

Question 10

What demographic population has the highest rate of incidence of cystic fibrosis?

Answer 10

caucasians

Question 11

what is cystic fibrosis?

Answer 11

an inherited disorder of an ion transport that affects fluid secretion in exocrine glands and in the epithelial lining of the respiratory, gastrointestinal, and reproductive tracts

Question 12

what are some clinical features of cystic fibrosis?

Answer 12

chronic lung disease secondary to recurrent infections, pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction, and male infertility

Question 13

what is the most common lethal genetic disease that affects caucasian populations?

Answer 13

cystic fibrosis

Question 14

the normal cystic fibrosis transmembrane regulator (CFTR) consists of what?

Answer 14

two transmembrane domains (channel), two nucleotide-binding domains (NBDs), and a regulatory R domain

Question 15

what does the most common mutation in the CFTR gene result in?

Answer 15

defective protein folding in the golgi/endoplasmic reticulum and degradation of CFTR before it reaches the cell surface

Question 16

what is the pathogenesis of respiratory and intestinal complications in cystic fibrosis seem to stem from?

Answer 16

an isotonic but low-volume surface fluid layer. In the lungs, this dehydration leads to defective mucociliary action and the accumulation of hyperconcentrated viscid secretions that obstruct the air passages and predispose to recurrent pulmonary infections

Question 17

CFTR regulates what?

Answer 17

transport of bicarbonate ions; pancreatic insufficiency, a feature of classic cystic fibrosis, is virtually always present when there are CFTR mutations with abnormal bicarbonate conductance

Question 18

What is cystic fibrosis like in patients with non-classic cystic fibrosis?

Answer 18

the disease is quite mild and does not seriously disturb growth and development

Question 19

In all variants of cystic fibrosis, what are the sweat glands like?

Answer 19

they are morphologically unaffected

Question 20

pancreatic insufficiency, a feature of classic cystic fibrosis, is virtually always present when there are CFTR mutations with abnormal bicarbonate conductance; what happens to the pancreas in more severe cases?

Answer 20

in more severe cases, the ducts of the pancreatic exocrine glands are completely plugged; atrophy of the exocrine portion of the pancreas may occur

Question 21

what does loss of the pancreatic exocrine secretion impair?

Answer 21

fat absorption, and the associated vitamin A deficiency may contribute to squamous metaplasia of the lining epithelium of the ducts in the pancreas

Question 22

What could thick viscid plugs of mucus in the small intestines of infants cause?

Answer 22

small-bowel obstruction known as meconium ileus

Question 23

What is the most serious complication of cystic fibrosis?

Answer 23

the pulmonary changes

Question 24

What are the three most common organisms responsible for lung infections in CF patients?

Answer 24

staphylococcus aureus, Haemophilus influenza, and Pseudomonas aeruginosa

Question 25

of the Burkolderia cepacia complex, which species are the most common in cystic fibrosis patients?

Answer 25

B. cenocepacia

Question 26

what are other opportunistic bacterial pathogens in CF patients?

Answer 26

stenotrophomonas maltophilia and nontuberculous mycobacteria

Question 27

what symptoms of CF typically appear at birth-if they do?

Answer 27

meconium ileus and intussusception

Question 28

when does liver disease typically present in patients with CF?

Answer 28

during puberty

Question 29

how can you diagnose CF?

Answer 29

characteristic clinical findings, sweat chloride test, immunoreactive trypsinogen, CFTR gene sequencing, and nasal transepithelial potential difference

Question 30

Patients with pancreas-sufficient CF have what?

Answer 30

recurrent bouts of pancreatitis associated with acute abdominal pain and occasionally life-threatening complications

Question 31

Besides the exocrine gland dysfunction in CF patients, what also could be occurring in the pancreas?

Answer 31

endocrine pancreatic insufficiency (causing DM)

Question 32

What is the most common cause of death in CF patients?

Answer 32

persistent lung infections, obstructive pulmonary disease, and cor pulmonale

Question 33

when might you suspect that CF testing is needed in a child?

Answer 33

if they have recurrent sinonasal polyps

Question 34

What is the second leading cause of CF patients?

Answer 34

significant liver disease

Question 35

how does liver disease in CF patients typically present?

Answer 35

obstruction of the common bile duct may occur due to stones or sludge; it presents with abdominal pain and acute onset of jaundice

Question 36

Why are 95% of males with CF infertile?

Answer 36

as a result of obstructive azoospermia due to congenital bilateral absence of the vas deferens

Question 37

What are three ways that have shown to be major improvements in the management of acute and chronic complications of CF?

Answer 37

potentiators, correctors, and amplifiers

Question 38

what is the role of the potentiators?

Answer 38

these agents keep the “gate” of the CFTR channel open

Question 39

what is the role of the correctors?

Answer 39

these agents assist in proper folding of the CFTR protein

Question 40

what is the role of the amplifiers?

Answer 40

these agents increase the amount of the CFTR protein the cell makes

Question 41

What is SIDS?

Answer 41

the sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation including performance of complete autopsy, examination of the death scene, and review of clinical history

Question 42

what type of diagnosis is SIDS?

Answer 42

a diagnosis of exclusion

Question 43

Many cases of sudden death in infancy may have ab unexpected anatomic or biochemical basis at autopsy. How should these be labeled?

Answer 43

not as SIDS but rather as sudden unexpected infant death (SUID)

Question 44

What is the triple risk model of SIDS?

Answer 44

1) vulnerable infant 2) a critical developmental period in homeostatic control and 3) an exogenous stressor

Question 45

What is the most common finding during an autopsy of an infant that actually died from SIDS?

Answer 45

petechiae