Inborn Errors of Metabolism 2

Question 1

Emergent Care (8)

Answer 1

a. Correct hypotension
b. NPO (reverse catabolism with D5-D10)
c. Correct hypoglycemia
d. Correct metabolic acidosis
e. Dialysis/lactulose – high/toxic NH4
f. Treat infection
g. Treat dehydration
h. Rule out sepsis (start abx is unsure)

Question 2

Detailed history to get with suspected IEMs (8)

Answer 2

a. Feeding hx
b. Describe seizures
c. Fevers
d. Respiratory hx
e. Weight gain
f. Milestones
g. Family history
h. Mom’s GsPs

Question 3

Physical Exam with IEMs (4)

Answer 3

1. Dysmorphology does not rule out IEM (note this)
2. Neuro
   i. Levels of alertness
   ii. Abnormal movements
   iii. Tone
3. Liver
   i. HSMegaly
   ii. Jaundice
4. Odor

Question 4

Lab Management (8)

Answer 4

1. ABG – acidosis
2. BMP, Ca and LFTS
3. NH4
4. Lactate
5. Pyruvate
6. UA – ketones, OA, AA
7. Newborn Screening (NBS) results
8. LP- r/o meningitis but send lactate STAT, Amino Acid levels

Question 5

Emergency Management (7)

Answer 5

1. Correct hypotension
2. NPO (reverse catabolism with D5-D10)
3. Correct hypoglycemia
4. Correct metabolic acidosis
5. Dialysis/lactulose of high/toxic NH4
6. Treat infection/dehydration
7. Rule out sepsis (start abx) if uncertain

Question 6

PKU Overview (4)

Answer 6

1. IEM of AA metabolism (1:15,000)
2. Asymptomatic in the neonate – clinically well!
   a. Untreated PKU does not cause symptoms in the neonate
3. Result of accumulating phenylalanine
4. Clinically well but irreversible brain damage occurs

Question 7

PKU Presentation (2)

Answer 7

1. Neuro- MR, seizures, spastic limbs

2. Mousy odor

Question 8

PKU Treatment (3)

Answer 8

1. Abnormal NBS → stop formula/BM→IV hydration or enteral feeds with electrolyte solutions→ Phenylalanine restricted diet (special formulas available)
2. Well established treatment that prevents MR
3. Refer to genetics and dietician

Question 9

Urea Cycle Disorder: Overview (7)

Answer 9

1. Protein Metabolism disorder
2. Protein catabolism produces nitrogen as waste product
3. Accumulation of nitrogen and toxic metabolites (ammonia) –> lead to neurologic sequelae
4. No acidosis (respiratory alkalosis)
5. No ketones (unlike organic acidemia)
6. No hypoglycemia
7. Yes hyperammonemia with normal anion gap and glucose

Question 10

Urea Cycle Disorder: Labs (3)

Answer 10

a. Ammonia level
b. Blood gas
c. Glucose level

Question 11

Urea Cycle Disorder: Treatment (6)

Answer 11

1. Remove ammonia
   * Na phenylacetate/Na benzoate (nitrogen scavengers)
2. Hydration with D10 + electrolytes
3. D/C all protein x 24 hours—calories from CHO and fat
4. Give arginine (deficient normal product of urea cycle)
5. Protein restriction for life
6. Liver transplant

Question 12

Urea Cycle Disorder: Prognosis (2)

Answer 12

1. Even with Treatment, many will die

2. Definitive treatment: liver transplant

Question 13

Protein Metabolism Disorder – Organic Acidemia Propionic Acidemia: Presentation (6)

Answer 13

a. Healthy NBrapidly ill
b. Ketoacidosis, poor feeding
c. Vomiting, dehydration
d. Hypotonia, lethargy
e. Tachypnea, seizures
f. Coma, unusual odors

Question 14

Protein Metabolism Disorder – Organic Acidemia Propionic Acidemia: Labs (4)

Answer 14

1. urine for organic acids
2. Ketonuria (in the newborn)- pathognomonic for IEM Neutropenia
3. +/- hyperammonemia
4. Abnormal acylcarnitine

Question 15

Protein Metabolism Disorder – Organic Acidemia Propionic Acidemia: Treatment (5)

Answer 15

1. Stabilize
2. Get rid of organic acid intermediates, and ammonia→hemodialysis
3. Carnitine
4. After stabilization, may resume oral feeds
5. Consult dietitian, and metabolic specialist

Question 16

Lysosomal Storage Disorder (MPS): Pathophysiology (4)

Answer 16

1. Rare group of lysosomal storage disorders of glycosaminoglycan (GAG) catabolism.
2. Deficiency of a specific lysosomal enzyme
   * This leads to an accumulation of partially degraded GAG (GAG fragments) due to a deficiency of a specific lysosomal enzyme –> causing progressive cellular damage in multiple organ systems → eventually causing organ failure.
3. Many types -Most of the MPS disorders are autosomal recessive with the exception of MPS II which is an X-linked recessive disorder affecting males.
4. Presentations within each type range mild (later occurrence) – to – severe

Question 17

Lysosomal Storage Disorder (MPS): Overview (3)

Answer 17

1. Attenuated MPS I can go undiagnosed for years and there is no cognitive impairment
2. Severe MPS I may not be diagnosed until after 12 month to 18 months
3. Different types—most autosomal recessive

Question 18

Lysosomal Storage Disorder (MPS): Types (8)

Answer 18

1. MPS 1 is due to the deficiency of lysosomal enzyme α-L-iduronidase
   * the patient accumulates glycosaminoglycan within lysosomes and there is multi-organ dysfunction and damage as a result (Hurler, Hurler-Scheie, Scheie syndrome)
2. MPS II or Hunter syndrome: is a deficiency of Iduronate-2-sulphatase
3. MPS III A-D is Sanfilippo syndrome
   * with each subtype having a deficiency of different enzymes.
4. MPS IV A, B, is Morquio syndrome
5. MPS VI is Maroteauz-Lamy syndrome
6. MPS VII is Sly syndrome.
7. MPS VIII is no longer used since it was a single case report that was classified as a MPS II.
8. MPS IX is a deficiency of Hyaluronane.

There are different presentations within each type ranging from mild and occurring later to severe

Question 19

Lysosomal Storage Disorder (MPS): Signs and Symptoms (11)

Answer 19

1. Course facial features
   i. Enlarged tongue
   ii. Full lips
   iii. Flat nasal bridge
   iv. Become more obvious overtime
2. Corneal clouding → vision loss
3. Sensorineural hearing loss
4. Communicating hydrocephalus → over months
5. Progressive cognitive impairment
   i. Neurodegenerative disorder in severe MPS 1
   ii. Early development normal →delay is obvious 1-2 years of age
6. Delay onset of language skills
7. Recurrent upper respiratory tract infections with otitis
8. Snoring and coarse breathing occur due to adenoidal and tonsillar enlargement
9. Restrictive lung disease with sleep apnea and asthma
10. Progressive skeletal and joint disease leading to:
    i. dysostosis multiplex, scoliosis, kyphosis, and hip dislocation
    ii. Short stature
11. Recurrent inguinal hernia

Question 20

Carbohydrate Metabolism Galactosemia (4)

Answer 20

1. Galactose is found in food- body metabolizes lactose (from milk) into galactose and glucose
2. Inherited disorder that affects the breakdown of galactose.. There is a lack of the enzyme (galactose-1-phosphate uridyl transferase)which helps the body break down the galactose it then builds up and becomes toxic causing organ damage
3. The build up of galactose causes:
   a. Liver – hepatomegaly & Jaundice
   b. Kidney – failure
   c. Growth and Development - stunted physical and mental growth Eyes – cataracts
4. If the condition is not treated there is a 70% chance of death.

Question 21

Signs and Symptoms of Fatty Acid Oxidation Disorders (18)

Answer 21

1. Extreme sleepiness
2. Behavior changes
3. Irritable mood
4. Poor appetite
5. Fever
6. Nausea
7. Diarrhea
8. Enlarged heart
9. Muscle weakness
10. Heart failure
11. Recurrent episodes of hypoglycemia
12. Lethargy
13. Hypotonia
14. Failure to thrive
15. Persistent vomiting
16. Hepatomegaly
17. Rhabdomyolysis
18. Reye syndrome-like episodes

Question 22

IEM Overall Summary (5)

Answer 22

1. Most present with metabolic acidosis + hyperammonemia
2. Request for specific lab studies
3. Consult metabolic specialist
4. Initial therapy- stabilize patient!
5. Long term treatment- based on specific IEM

Question 23

IEM Treatment depends on (7)

Answer 23

a. Dietary Restriction
b. Supplement deficient product
c. Stimulate alternate pathway
d. Supply vitamin co-factor
e. Organ transplantation
f. Enzyme replacement therapy
g. Gene Therapy