Pediatrics

Question 1

Baby presents with jaundice, voiting, irritability, and somnolene after switching from breastmilk to baby food. Labs show hypoglycemia, ketosis, and reducing sugars in urine. What is the most likely diagnosis.

Answer 1

Based on timecourse (switch from breastmilk), hypoglycemia and urine sugars, suspect aldolase B deficiency (aka hereditary fructose intolerance)

In this disorder, fructose-1-P accumulates. It depletes the cell’s ATP stores and causes phosphate trapping. Without ATP, gluconeogenesis and glycogenolysis stop working, leading to hypoglycemia, vomiting, and liver problems such as hepatomegaly, jaundice, and even cirrhosis.

Question 2

What are the key enzymes in fructose metabolism?

Answer 2

Fructose first enters liver cells through the GLUT-5 transporter, which works via facilitated diffusion. Then the following enzymes work their magic, in order:

Fructokinase: Conversion of fructose to fructose-1-P. This step requires adenosine triphosphate (ATP) to provide the phosphate.

Aldolase B: Cleavage of fructose-1-P to dihydroxyacetone phosphate and glyceraldehyde.

Triose phosphate isomerase and triose kinase: Conversion of dihydroxyacetone phosphate and glyceraldehyde to glyceraldehyde-3-P.

Glyceraldehyde-3-P can then proceed through glycolysis as usual

Question 3

What problems occur downstream of aldolase B deficiency

Answer 3

aldolase converts fructose-1-P to metabolites, therefore its deficiency leads to fructose-1-P accumulation. It depletes the cell’s ATP stores and causes phosphate trapping. Without ATP, gluconeogenesis and glycogenolysis stop working, leading to hypoglycemia, vomiting, and liver problems such as hepatomegaly, jaundice, and even cirrhosis. Fructose-1-P also competitively inhibits glycogen phosphorylase, the first step in glycogenolysis, thus exacerbating hypoglycemia.

Question 4

What types of sugars should be avoided in patients with fructose metabolism disorders?

Answer 4

fructose, sucrose, sorbitol

Question 5

describe galactose metabolism

Answer 5

Galactose enters cells through SGLT1, the same sodium-dependent transporter used to take up glucose. Inside cells, galactose metabolism proceeds with the help of the following enzymes (Figure 2):

Galactokinase: Converts galactose to galactose-1-P. This step requires ATP to provide the phosphate.

Galactose-1-phosphate uridylyltransferase (GALT): Converts galactose-1-P to glucose-1-P by switching the attached groups of galactose-1-P and UDP-glucose. In Figure 2, this enzyme is labeled simply as uridylyltransferase.

Aldose reductase: Converts galactose to galactitol via the polyol pathway. This is the same enzyme that converts glucose to sorbitol.

Question 6

what enzyme is deficient in maple syrup urine disease

Answer 6

Alpha-ketoacid dehydrogenase (ie branched chain alphe ketoacid dehydrogenase or BCKDH)

Question 7

Normal serum Ammonia in the setting of a suspected inborn error of metabolism would rule out which ones?

Answer 7

excludes a urea cycle disorder or an organic acidemia.

Question 8

presence of ketones in the urine in the setting of a suspected inborn error of metabolism would rule out which ones?

Answer 8

rules out a beta-oxidation disorder which would cause hypoketosis

Question 9

what are the key features and types of urea cycle disorder

Answer 9

Key features include

1. presentation in the first 24-48 hours after birth (b/c breastmilk contains proteins)
2. severe hyperammonemia,
3. absence of acidosis or other metabolic derangements.

The most common urea cycle disorder is the deficiency of the enzyme ornithine transcarbamylase –> As a result, ammonia cannot be metabolized into urea

Question 10

Many inborn errors of metabolism present in the first few days of life. Two key exceptions are (1) ______________ and (2) ________________

Answer 10

Two key exceptions are (1) glycogen storage disease type I (usually 3 to 6 months) and (2) hereditary fructose intolerance (occurs when weaned from breastfeeding).

Question 11

what infection is characterized by the Triad of: hydrocephalus, intracranial calcifications, and chorioretinal lesion

Answer 11

toxoplasmosis

Question 12

what TORCH infection is characterized by triad of: hearing loss, patent ductus arteriosus (continuous murmur), and cataracts

Answer 12

rubella

mn: a murmur sounds like a RUBbing noise (RUBella)

+ssRNA virus

Question 13

what TORCH infection is characterized best by: sensorineural hearing loss, hepatosplenomegaly +/- jaundice, thrombocytopenia, microcephaly

Answer 13

CMV

Question 14

By what age(s) do the primitive reflexes typically disappear?

Answer 14

Moro reflex by 3 months, rooting reflex by 4 months, palmar reflex by 6 months, and Babinski sign by 12 months of age (the Babinski reflex disappears when the corticospinal tract becomes myelinated)

**note these ages are all factors of 12

Question 15

what are the two key causes of failure to pass meconium within first 48 hrs of life

Answer 15

cystic fibrosis and Hirschsprung disease

Question 16

What is the biochemical profile for OTC deficiency?

Answer 16

OTC deficiency = ornithine transcarbamylase deficiency

OTC converts Ornithine and carbamoyl phosphate to citrulline

Profile: hyperammonemia, ketosis, urine orotic acid, absent hypoglycemia, absent acidosis

Question 17

What is the biochemical profile for PDC deficiency?

Answer 17

PDC = pyruvate dehydrogenase complex

converts pyruvate to acetyl CoA

Profile: alanine in urine and serum, hyperammonemia, severe lactic acidosis, high serum pyruvate

Question 18

What is the biochemical profile for Lesch Nyhan syndrome?

Answer 18

This syndrome is a deficiency in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), which catalyzes the conversion of Hypoxanthine and phosphoribosyl pyrophosphate to inosine monophosphate

Profile: uric aciduria, absent hyperammonemia.

sx: renal calculi, neurologic dysfunction (spasticity), delayed physical and mental development, self-injurious behavior (bruising), hemolytic anemia, and immune deficiency manifesting after 6 months of life.

Question 19

What is the biochemical profile of phenylketonuria (PKU)

Answer 19

deficiency of Phenylalanine hydroxylase

converts phenylalanin –> tyrosine

intellectual abnormalities, seizures (from decreased tyrosine), growth retardation, dermatitis, fair skin, or a musty body odor

Profile: elevated serum phenylalanine (+phenylacetate in urine), absent hyperuricemia, absent hyperammonemia

Tyrosine is nutritionally essential to patients with PKU and must be supplemented.

Question 20

Orotic acid concentrations are increased in patients with ________________ and _____________________

Answer 20

uridine monophosphate synthase deficiency (orotic aciduria) or ornithine transcarbamylase (OTC) deficiency.

Question 21

which enzyme deficiency (IEM) can cause severe combined immunodeficiency

Answer 21

adenosine deaminase deficiency

Question 22

what is the biochemical profile for MCAD deficiency?

Answer 22

Medium-chain acyl-CoA dehydrogenase (MCAD) degrades medium-chain fatty acids into acetyl-CoA in the mitochondria (β-Oxidation)

in patients with MCAD deficiency, a deficit of acetyl-CoA develops, which leads to hyperammonemia, hypoglycemia without compmensatory ketosis, vomiting, and lethargy, (usually presenting after period of fasting or high ATP demand such as infection)

Question 23

What is the biochemical profile for OTC deficiency

Answer 23

Ornithine transcarbamylase deficiency (OTC)

Converts ornithine and carbamoyl phosphate to citrulline

Buildup of carbamoyl phosphate → orotic acid

Profile: orotic acid in the urine, hyperammonemia, failure to thrive, developmental delay

don’t confuse with orotic aciduria which does not present with hyperammonemia

Question 24

which IEM are autosomal recessive

Answer 24

basically all the urea cycle disorders

Question 25

how would you differentiate between OTC deficicency and orotic aciduria

Answer 25

orotic aciduria has no hyperammonemia and causes megaloblasic anemia

this is not true for OTC def.

Question 26

what birth defects have multifactorial inheritance

Answer 26

cleft lip and congenital heart defects

Question 27

what is 22q11.2 deletion syndromes

Answer 27

loss of TBX1 gene and COM genes as a result of a microdeletion at the 22q11 chromosome.

Results in:

• Cleft palate
• Abnormal facies
• Thymic aplasia which results in
• T-cell deficiency
• Cardiac defects
• Hypocalcemia secondary to
• parathyroid aplasia

mnemonic = CATCH-22

examples: DiGeorge and velocardiofacial syndrome

Question 28

Chr 22q11.2 duplication syndrome

Answer 28

Affected individuals may have developmental delay, intellectual disability, slow growth
leading to short stature, and weak muscle tone

Question 29

What congenital defects result from failure of the GI lumen to recanalizate

Answer 29

Esophageal atresia (without fistula), biliary atresia, and duodenal stenosis are all caused by abnormal recanalization

A normal stage of development of the GI tube is the proliferation of the lining endoderm cells so that they temporarily fill the lumen. This is followed by a subsequent loss of these cells, leading to recanalization (ie, reopening the lumen).

Question 30

the steeple sign on XR is indicative of which upper airway obstruction

Answer 30

croup (acute laryngotracheobronchitis)

Question 31

what is bronchopulonary dysplasia

Answer 31

chronic lung disease primarily found in premature infants exposed to prolonged mechanical ventilation and oxygen therapy for neonatal RDS

Question 32

what ligement is torn in radial head subluxation (nurse maid elbow)

Answer 32

annular ligament

Pain results from pinching of the annular ligament in the elbow joint, and pronation/

supination becomes very limited

ddx: supracondylar fracture

Question 33

risk factors for hip dysplasia

Answer 33

female gender, Native American heritage, first born status, and breech birth

Question 34

injury to the surgical neck of the humerus risks damage of what nerve

Answer 34

axillary nerve

mn: you need help (ancillary–> axillary) in surgery

also, a shoulder dislocation would cause injury to axillary nerve

Question 35

what nerves and/or arteries ar at risk in a supracondylar fracture and what is the dreaded complication?

Answer 35

Supracondylar fractures are the most common arm injury in ages 5-7, they can injure the median nerve, which can present as loss of wrist flexion, thumb opposition, or lateral finger flexion.

damage to the brachial artery is also at risk

XR shows sail sign

***the dreaded complication is volkmann ischemic contracture

Question 36

what is leg calve perthes disease

Answer 36

Idiopathic avascular necrosis of the femoral head of insidious onset causing hip pain that may cause child to limp more common in males and presents ages 5-7. XR can be normal

Question 37

enuresis is defined as

Answer 37

Enuresis is clinically defined as having

urinary incontinence at >5 years of age. Most children become toilet-trained between 2-4 years of age.

Treatments include reassurance, if pt is 5+ yo, can do behavioral conditioning with bedwetting alarms, and occasionally, medication of Desmopressin acetate

Question 38

After stabilization, what is the management of croup?

Answer 38

Racemic nebulized epinephrine

this will quickly reduce symptom severity and should be followed up by the administration of glucocorticoids (usually dexamethosone), which will provide longer lasting relief.

Question 39

most common pathogen in epiglottitis

Answer 39

H. influenzae

and

S. aureus

Question 40

What are The most common causes of bacterial upper respiratory infection

Answer 40

The most common causes of bacterial upper respiratory infection are

1. Streptococcus pneumoniae (gram pos encapsulated, lancet-shaped diplococci)
2. Haemophilus influenzae (gram-negative coccobacilli), and
3. Moraxella catarrhalis (gram-negative, aerobic, oxidase-positive diplococcus that is unable to metabolize maltose)

Question 41

what is the pathophys of cleft lip vs cleft palate

Answer 41

Failure of the maxillary processes and medial nasal swelling to fuse

This defect results from abnormal development during the 6th week of gestation, when the maxillary prominences grow medially and fuse first with the lateral and then the medial nasal prominence.

The secondary palate is formed when the lateral palatine shelves eventually fuse after moving from a horizontal to vertical orientation at about the 8th week of development. Failure of the shelves to either change in orientation (e.g., as in Pierre Robin syndrome), fuse together, or fully join the nasal septum leads to a cleft palate. While often coincidental with this patient’s defect, a cleft palate develops later than the 6th week of gestation and does not involve the maxillary prominences.