Inborn errors of metabolism

Question 1

PKU is a deficiency of what?

Answer 1

Phenylalanine hydroxylase (PAH)

Question 2

What is the treatment of PKU?

Answer 2

Remove phenylalanine from diet

Question 3

What reaction does PAH regulate?

Answer 3

Phenylalanine -> tyrosine

Question 4

Tyrosine is a precursor for what?

Answer 4

DA, L-dopa, melanin

Question 5

What is the inheritance pattern of PKU?

Answer 5

Aut Rec

Question 6

What is the phenotype of PKU?

Answer 6

Hyperphenylalaninemia, mental retardation, white matter hyperintensities, seizures, light hair and skin

Question 7

What kind of amino acids are found in the urine of a patient with MSUD?

Answer 7

Branched-chain ketoacids

Question 8

What is the inheritance pattern of MSUD?

Answer 8

Aut Rec

Question 9

MSUD is a deficiency of what?

Answer 9

Branched chain alpha ketoacid dehydrogenase (BCKD)

Question 10

What is the acute treatment of MSUD?

Answer 10

Eliminate dietary protein intake. Treat cerebral edema if present. Hemodialysis maybe..

Question 11

What is the chronic therapy of MSUD?

Answer 11

Protein restricted diet supplemented with branched chain amino acid free medical foods (MSUD “coolers”).

Question 12

Tyrosenemia type I is a deficiency of what?

Answer 12

Fumarylacetoacetate hydrolase (FAH)

Question 13

What is the inheritance pattern of Tyrosenemia type I?

Answer 13

Aut Rec

Question 14

What are the 3 presenting forms of Tyrosenemia type I?

Answer 14

1. 1-6mo: liver disease
2. late infancy: rickets due to renal tubulopathy (Fanconi syndrome) with no obvious liver failure
3. porphyria-like attack at any age

Question 15

In Tyrosenemia type I, which molecules build up which are toxic to the liver and nerves?

Answer 15

Fumarylacetoacetate and succinylacetone

Question 16

What is the treatment of Tyrosenemia type I?

Answer 16

NTBC which inhibits an enzyme which causes further buildup of tyrosine but prevents production of FAA and succinylacetone. Restrict dietary tyrosine.

Question 17

Palmoplantar keratosis is a feature of which disease?

Answer 17

Tyrosenemia type I; buildup of tyrosine

Question 18

What can Tyrosenemia type I do to the eye?

Answer 18

Tyrosine can crystalize in the cornea

Question 19

What is the clinical presentation of Alkaptonuria?

Answer 19

Black urine, black pigmentation of cartilage and collagen, degenerative arthritis from fourth decade.

Question 20

Which amino acidopathy presents similar to Marfan if left untreated?

Answer 20

Homocysteinuria

Question 21

In homocysteinuria, which two molecules are elevated in blood and urine?

Answer 21

Homocysteine and methionine

Question 22

Homocysteinuria is a deficiency of what?

Answer 22

Cystathionine b-synthase (CBS)

Question 23

Thromboembolism can be a manifestation of which amino acidopathy?

Answer 23

Homocysteinuria

Question 24

Premature atherosclerotic disease can be a manifestation of which amino acidopathy?

Answer 24

Homocysteinuria

Question 25

What is the inheritance pattern of Homocysteinuria?

Answer 25

Aut Rec

Question 26

Which vitamin is given as a treatment for Homocysteinuria?

Answer 26

B6 (Pyridoxine)

Question 27

What is the treatment of Homocysteinuria?

Answer 27

B6 (if responsive), restrict dietary protein, oral betaine

Question 28

What are the general manifestations of urea cycle disorders?

Answer 28

Encephalopathy, coma, irreversible neurologic damage, or death.

Question 29

Why is it difficult to detect a urea cycle disorder?

Answer 29

Because ammonia levels must be checked. Always check ammonia in a coma.

Question 30

What are some common triggers of hyperammonemic crises in UCD patients?

Answer 30

Infections, fevers, valproate, vomiting, lots of exercise, chemotherapy.

Question 31

What is the most common urea cycle disorder?

Answer 31

Ornithine Transcarbamylase (OTC) Deficiency

Question 32

What is the inheritance pattern of OTC Deficiency?

Answer 32

X-linked

Question 33

What is the treatment for acute OTC Deficiency?

Answer 33

Ammonia scavenging agents

Question 34

What are two ammonia scavenging agents?

Answer 34

Sodium phenylacetate and Sodium benzoate

Question 35

What are some treatment strategies for OTC Deficiency?

Answer 35

Dietary protein restriction, ammonia scavengers, consider liver transplant

Question 36

The majority of lysosomal storage diseases (LSDs) are inherited in what fashion? What is the exception?

Answer 36

Aut Rec. Exceptions are Fabry and Hunter disease (X-linked).

Question 37

Are LSDs usually acute or gradual in onset?

Answer 37

Gradual - buildup of molecule and then organ defect leads to dysfunction.

Question 38

What is the deficient enzyme in Fabry disease?

Answer 38

alpha-galactosidase

Question 39

What is the deficient enzyme in Gaucher disease?

Answer 39

Glucocerebrosidase (beta-glucosidase)

Question 40

What is the deficient enzyme in Tay Sachs Type I?

Answer 40

Hexosaminidase A

Question 41

What is the incidence of all lysosomal storage diseases combined?

Answer 41

1:5,000

Question 42

Cherry red spots are indicative of which LSD?

Answer 42

Tay Sachs

Question 43

Blindness is a complication of which LSD?

Answer 43

Tay Sachs

Question 44

Renal failure is a complication of which LSD?

Answer 44

Fabry

Question 45

What are the skin manifestations of LSDs?

Answer 45

Courseness

Question 46

What are the skull (brain) manifestations of LSDs?

Answer 46

Macrocephaly and cognitive regression

Question 47

What are the eye manifestations of LSDs?

Answer 47

Corneal clouding and cherry red spot

Question 48

What are the ENT manifestations of LSDs?

Answer 48

Macroglossia with sleep apnea (complication)

Question 49

What are the liver manifestations of LSDs?

Answer 49

Hepatosplenomegaly with preserved hepatic function

Question 50

What are the renal manifestations of LSDs?

Answer 50

Proteinuria (Fabry)

Question 51

What are the skeletal manifestations of LSDs?

Answer 51

Dysostosis multiplex, joint stiffness, short stature

Question 52

What is Dysostosis Multiplex?

Answer 52

Abnormally bony structure on x rays; vertebral beaking, broad bases of metacarpals and phalanges, scoliosis

Question 53

"Crumpled tissue paper" appearance in cytoplasm of bone marrow cells is indicative of which LSD?

Answer 53

Gaucher

Question 54

An Erlenmyer flask deformity of bones is indicative of which LSD?

Answer 54

Gaucher type I - bone marrow infiltration

Question 55

What is the clinical presentation of Gaucher type I?

Answer 55

Fatigue, bony pain, enlarging abdomen, hepatosplenomegaly, anemia/low platelets.

Question 56

Which organs are involved in Gaucher?

Answer 56

Liver, spleen, bone marrow (no CNS)

Question 57

What is the treatment for Gaucher?

Answer 57

ERT

Question 58

What is the treatment for Tay Sachs?

Answer 58

Supportive

Question 59

What is the treatment for Fabry?

Answer 59

ERT

Question 60

What is the treatment for Pompe disease?

Answer 60

ERT

Question 61

What is the deficient enzyme in Pompe disease?

Answer 61

Alpha-glucosidase

Question 62

What is the clinical presentation of Tay Sachs type I?

Answer 62

Blindness, seizures, mental/motor deterioration, no hepatosplenomegaly

Question 63

What is the clinical presentation of Pompe disease?

Answer 63

Infant with progressive muscle weakness and LVH. Adult with proximal muscle weakness and respiratory weakness (sleep apnea).

Question 64

What is the clinical presentation of Fabry?

Answer 64

Acroparesthesia; pain in palms/soles, esp with fevers. Proteinuria and renal failure. Left ventricular hypertrophy/stroke. Dark red angiokeratomas (bathing suit distribution).

Question 65

What is the deficient enzyme in Hunter disease?

Answer 65

Iduronate sulfatase

Question 66

What is the deficient enzyme in Hurler disease?

Answer 66

Alpha iduronidase

Question 67

SCID is caused by a deficiency in what enzyme?

Answer 67

Adenosine deaminase (ADA)

Question 68

Lesch-Nyhan is caused by a deficiency in what enzyme?

Answer 68

HPRT