Ped Metabolic Illness

Question 1

How common are pediatric metabolic disorders?

Answer 1

1/200

Question 2

What is the prognosis for most of the pediatric metabolic disorders?

Answer 2

Lethal

Question 3

What common condition mimics pediatric metabolic disorders?

Answer 3

Sepsis
Birth trauma
HF

Question 4

What are the three conditions in which a metabolic disorder must be suspected?

Answer 4

• Neonates with unexplained, progressive disease after normal pregnancy
• All children with acute deterioration of general condition
• Children with ssx of acidosis or hypoglycemia

Question 5

What is the inheritance pattern of Type II hyperlipoproteinemia?

Answer 5

AD

Question 6

What is the inheritance pattern of Polycystic kidney disease?

Answer 6

AD

Question 7

What is the inheritance pattern of G6PD deficiency?

Answer 7

XLR

Question 8

What is the inheritance pattern of Hunter syndrome? What enzyme is defective in this? What metabolites accumulate? SSX?

Answer 8

XLR
iduronate-2-sulfatase (I2S).[1][2] The accumulated substrates in Hunter syndrome are heparan sulfate and dermatan sulfate

GAG buildup in face and abdo, but no eye

Question 9

What is the inheritance pattern of Duchenne’s muscular dystrophy? What is the pathophysiology of this?

Answer 9

XLR

Mutation in the dystrophin gene that is a part of the skeletal framework of muscle cells

Question 10

What is the inheritance pattern of Hurler’s syndrome? What enzyme is defective in this? What metabolites accumulate? SSX?

Answer 10

XLR
alpha-L iduronidase

Heparan sulfate and dermatan sulfate

MR, eye issues

Question 11

What is the most important part of the history to obtain if you suspect an inherited disorder of metabolism

Answer 11

Diet history

Question 12

What are the ssx of inborn?

Answer 12

Hypoglycemia
Metabolic acidosis
Lactic acidosis
Hyperammonemia

Question 13

Diaphoretic newborns should be suspicious for what?

Answer 13

IEM

Question 14

What is the ULN of ammonia for infants? How does this compare to adults?

Answer 14

95 Much higher than adults (35)

Question 15

What are the ssx of hyperammonemia?

Answer 15

Lethargy
Somnolence
Emesis
Szs

Question 16

What, generally, is the usual cause of hyperammonemia in children?

Answer 16

Urea cycle issues

Question 17

What is the drug of choice for treating seizures in infants? MOA?

Answer 17

Phenobarbital

increased flux of chloride ions into the neuron d/t increase in Cl channel opening duration

Question 18

What is MCAD deficiency? Cause? Ssx?

Answer 18

• AR, Medium-chain acyl-CoA dehydrogenase deficiency
• hypoketotic hypoglycemia and liver dysfunction, often preceded by extended periods of fasting or an infection with vomiting.

Question 19

What is the most common cause of sepsis in newborn females?

Answer 19

UTI

Question 20

What is the cause of PKU? SSX?

Answer 20

Deficiency in phenylalanine hydroxylase, causing a musty baby odor, and MR if not treated

Question 21

What is the amino acid that pts with PKU must avoid? What must they take a supplement for?

Answer 21

Avoid F

Increase Y

Question 22

What is the inheritance pattern of PKU?

Answer 22

AR

Question 23

How do you diagnose PKU?

Answer 23

Plasma Phe level more than 20 mg/dL

Question 24

What is the treatment for PKU?

Answer 24

Restrict F intake

Lofenalac

Question 25

What is Lofenalac?

Answer 25

Baby formula that lacks phenylalanine for PKU pts

Question 26

What is malignant hyperphenylalaninemia?

Answer 26

normal phenylalanine hydroxylase (PAH) activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB), a cofactor of PAH

Question 27

What are the early ssx of PKU?

Answer 27

- Choking spells with trying to swallow - Vomiting - Abnormal neurological development

Question 28

What are the Phe levels for mild, moderate, and severe PKU?

Answer 28

``` Mild = less than 600 Mod = 600-1200 Severe = 1200+ ```

Question 29

What is the inheritance pattern of PKU?

Answer 29

AR

Question 30

What is the incidence of PKU?

Answer 30

1:15000

Question 31

What is the allowable amount of Phe for PKU pts?

Answer 31

250-350 mg

Question 32

What are the ssx of maternal PKU (untreated PKU in the mother)?

Answer 32

Microcephaly Low birth weight MR

Question 33

What level of Phe in a PKU mother is bad for the infant?

Answer 33

More than 360 microM

Question 34

What is the cause of galactosemia? Inheritance? Ssx?

Answer 34

- AR - Galactokinase, or galactose-1-uridyl transferase - ssx: hepatomegaly, MR, cataracts,

Question 35

What causes the cataracts in pts with galactosemia?

Answer 35

High galactose levels are converted in eye by aldose reductase to galactitol, but this is not suitable for polyol dehydrogenase (the next enzyme in the pathway) so builds up.

Question 36

What is the incidence of galactosemia?

Answer 36

1:75000

Question 37

What is the usual presentation of children with galactosemia?

Answer 37

Physically normal at birth, but vomiting, diarrhea, HSN, jaundice and cataracts

Question 38

What type of bacteria are patients with galactosemia susceptible to?

Answer 38

Gram negatives

Question 39

What is the urinary finding of galactosemia?

Answer 39

Reducing substance (sugar)

Question 40

What is the test to confirm galactosemia?

Answer 40

Red cell enzyme test

Question 41

What is the treatment for galactosemia?

Answer 41

Avoid breast milk and other sources of galactose---soy formula

Question 42

What is the prognosis for galactosemia?

Answer 42

Mortality in neonatal period of 20%, but good if treated

Question 43

What are the three major things to monitor for with pts with galactosemia?

Answer 43

- E. coli sepsis risk - Treat jaundice PRN - Monitor for developmental delay

Question 44

What is the presentation of MCAD deficiency?

Answer 44

Emesis after periods of fasting (sleeping)

Question 45

What are the pH, pCO2, and HCO3 levels with organic acidemias? Urea cycle disorders?

Answer 45

All low for organic acidemias pH is high with urea cycle disorders, but HCO3 and pCO2 are low

Question 46

What is the cause of homocystinuria? What is the enzyme that causes this involved in? Ssx?

Answer 46

Deficiency in cystathionine beta synthase--involved in the pathway of converting methionine to cysteine Dislocation of optic lens, MR,

Question 47

What is the treatment for homocystinuria?

Answer 47

B6 supplementation

Question 48

What is the cofactor needed for Phenylalanine hydroxylase?

Answer 48

DHP

Question 49

How does PKU cause MR?

Answer 49

Inhibits the transport of other amino acids across the BBB

Question 50

What molecule can all glucogenic amino acids be broken down into? Ketogenic?

Answer 50

- Oxaloacetate = glucogenic | - Acetyl-coa

Question 51

What are the two purely ketogenic amino acids?

Answer 51

Leucine | Lysine

Question 52

What is familial hyperinsulinemic hypoglycemia type 6?

Answer 52

Insensitivity of E-dehydrogenase, leading to continued catabolism of AAs. The increase in ATP leads the pancreas to overproduce insulin, causing hypoglycemic hyperinsulinemia

Question 53

What is the only reaction in the body N5-THF back to THF? What enzyme catalyzes this reaction?

Answer 53

Conversion of homocysteine to methionine | Methionine synthase

Question 54

What is the cause of maple syrup urine disease?

Answer 54

Inability to break down branched chain amino acids (Isoleucine, Leucine, Valine) ("I Love Vermont Maple syrup")

Question 55

What is alkaptonuria, and what causes it? SSx?

Answer 55

- Homogentisate oxidase defect | - Urine turns black on exposure to air, and ochronosis

Question 56

What is the molecule that can be donated from the urea cycle to the TCA cycle?

Answer 56

Fumarate

Question 57

What is the molecule that can be donated from the TCA cycle, to the urea cycle?

Answer 57

OXA --(AST)-- D (AST) is the enzyme

Question 58

What is the cause of citrullinemia? Ssx? Treatment?

Answer 58

Defect in argininosuccinate synthetase,

Question 59

What is the cause of argininosuccinic aciduria? Ssx? Treatment?

Answer 59

Defect in argininosuccinate lyase

Question 60

What is the cause of hyperargininemia? Ssx? Treatment?

Answer 60

Arginase deficiency

Question 61

What is the major difference between hyperargininemia and other urea cycle defects?

Answer 61

Build up of ammonia leads to hepatic encephalopathy

Question 62

What is Adrenoleukodystrophy? What is the classical presentation? Prognosis? Gene?

Answer 62

ABCD1 gene--XLR disorder of peroxisomal beta-FA degradation. Leads to neuropathy d/t FA accumulation. Young male with acidosis, Hyperkalemia, hypotension, and neurological ssx.