IEM/Thermal Regulation

Question 1

Glycogen storage disease type I and II (enzymes)

Answer 1

Type I: glucose 6 phosphatase (Von Gierke)
Type II: lysosomal alpha-glucosidase (Pompe)

Question 2

Most common urea cycle defect; inheritance

Answer 2

Ornitihine carbamyl transferase, X-linked recessive

Question 3

Urea cycle clinical presentation; treatment

Answer 3

present in first few days of life with poor feeding, vomiting, apnea, and changes in mental status. Hyperammonemia, respiratory ALKALOSIS, normal serum glucose
Tx: remove infant’s nitrogen by limiting protein intake, administration of sodium benzoate or phenylacetate, or HD

Question 4

Niemann-Pick syndrome

Answer 4

congenital lipidosis, lysosomal storage disease. Macular cherry red spots, clear corneas, FOAM cells on BM biopsy.
Sphingomyelinase defect

Question 5

Inheritance of pyruvate dehydrogenase, clinical presentation

Answer 5

mitochondrial d/o
Developmental delay, poor muscle tone and weakness, seizures, ataxia, choreoathetosis, global cerebral atrophy
Absent CC, subtle facial dysmorphology. Narrow head with frontal bossing, wide nasal bridge, long philtrum, flared nostrils. Anion gap MA with elevate lactate and pyruvate levels

Question 6

Next step when suspect tyrosinemia

Answer 6

send serum and urine succinylacetone levels and urine reducing substances

Phenylalanine –> Tyrosine –> dopamine slash phenylpyruvate fumarate + acetoacetate

Question 7

Biotinidase deficiency (AR)

Answer 7

sx are result of decreased available biotin for enzymatic reactions.

IMMUNE dysfunction, alopecia, skin rash. NEURO dysfunction, seizures, hypotonia, lethargy, ataxia, blindness, hearing loss.

Tx oral biotin supplementation. Does NOT cause nystagmus

Question 8

Menkes disease

Answer 8

X-linked recess; brittle, steely, kinky hair. Disrupts nervous system and bone development. Dx – low ceruloplasmin and copper levels

Question 9

Non-ketotic hyperglycinemia

Answer 9

AR, defective cleavage of glycine eto ammonia

Question 10

Hyperammonemia differential dx

Answer 10

1. Acidosis and ketonuria
2. Acidosis without ketonuria
3. Absence of acidosis and ketonuria (Transient) – related to immaturity of N-acetylglutamate synthetase enzyme activity

Question 11

Homocystinuria

Answer 11

Optho: DOWNward dislocated lens, glaucoma, myopia
Bones: osteoporosis, scoliosis, increased tendency to fracture, TALL, arachnodactyly, decreased joint mobility
Neuro: DD, cognitive impairment, seizures
Heme: increased thrombosis and bleeding

Question 12

Treatment of Wilson’s disease

Answer 12

D-penicillamine (copper chelator)

Question 13

Biotin function

Answer 13

binds to carboxylases, enhances function

Question 14

Gaucher
Niemann Pick
Tay-Sach’s
N-acetylglutamate synthetase

Answer 14

Gaucher = Glucocerebrosidase – Gaucher cells in bone marrow

Niemann Pick = Sphingomyelinase – cherry red spots, FOAM CELLS in BM

Tay-sach’s – heosaminidase, cherry red spots, NORMAL BM
17A / D
N-acetylglutamate synthetase deficiency

Question 15

Urea cycle disorder

Answer 15

N-acetylglutamate synthetase
Carbamyl phosphate synthetase [both have normal or low orotic acid]
Ornithine carbamyl transferase
Arginosuccinic acid synthetase
Arginosuccinic lyase
Arginase

Question 16

Classic galactosemia

Answer 16

liver failure, hypoglycemia, LFTs up

NOT lactate elevated

Galactose-1 phosphate uridyl transferase (GALT) deficiency: Classic galactosemia, the most common and most severe form
Deficiency of galactose kinase (GALK)
Deficiency of galactose-6-phosphate epimerase (GALE)

Question 17

Name diagnostic test
Galactosemia
D/o of AA metabolism
Organic acidemia
Fatty acid oxidation defects
Glycogen storage diseases

Answer 17

Galactosemia – urine non-glucose reducing
D/o of AA metabolism – abnormal serum AA
Organic acidemia – abnormal urine organic acids
Fatty acid oxidation defects – abnormal acylcarnitnie
Glycogen storage diseases – increased serum ketones and lactate

Question 18

If sample not sent on ice, then ammonia will be _____

Answer 18

elevated

Question 19

How to diagnose fatty acid oxidation disorder?

Answer 19

Acylcarnitine profile is more informative in diagnosing fatty oxidation defects than total and free carnitine concentrations

Question 20

Organic acidemia features

Answer 20

metabolic acidosis and abnormal UOA

Question 21

Pyruvate metabolism or mitochondrial energy metabolism defects

Answer 21

metabolic / lactic acidosis

Question 22

Urea cycle defects lab test

Answer 22

Urea cycle defects: abnormal plasma amino acids

Question 23

Type I vs Type II glycogen storage disease

Answer 23

Type I: Glucose -6 – phosphatase, liver/kidney/GI, LACTIC ACIDOSIS, HM, neutropenia, FTT, diarrhea. Bleeding disorder.
Type II Pompe = lyososomal alpha-glucosidase – affects all organs, symmetric severe muscle weakness, cardiomegaly, HOCM, CHF.