Biochemical

Question 1

What types of metabolic disorders is hypoglycemia a sign of?

Answer 1

glycogen storage diseases, fatty acid oxidation disorders (others, these are main)

Question 2

What is the carrier frequency of PKU?

Answer 2

1/58

Question 3

For MSUD, what amino acids are not able to be broken down?

Answer 3

branched chain amino acids: leucine, isoleucine, valine

Question 4

What disorder is associated with a sweaty sock odor?

Answer 4

isovaleric acidemia

Question 5

What is the general treatment approach for urea cycle disorders?

Answer 5

control ammonia levels, excess calories so don’t break down protein

Question 6

What are the three types of Gaucher disease?

Answer 6

Type 1: Non neuropathic, childhood-adult onset, no neurodegeneration (more common in AJ)
Type 2: onset before age 2, rapidly progressive and lethal by age 2-3
Type 3: lethal by age 20-30

Rare prenatal lethal type
Rare: cardiac involvement only (valvular disease)

Question 7

What movement disorder is Gaucher associated with?

Answer 7

20-30x increased risk for Parkinson’s

Question 8

What type of mutation is associated with infantile onset of Tay Sachs disease?

Answer 8

biallelic null alleles

Question 9

What are the fasting times before symptom onset for glycogen storage diseases and fatty acid oxidation disorders?

Answer 9

GSD: 6-12 hours
FAO: 3-4 hours

Question 10

What causes neurologic dysfunction in urea cycle disorders?

Answer 10

hyperammonia

Question 11

What does presentation of organic acid disorders look like in the first days of life?

Answer 11

metabolic acidosis- early, before NBS comes back

Question 12

What organs are affected by mitochondrial disorders?

Answer 12

organs that use a lot of oxidative phosphorylation: brain, skeletal muscle, heart, liver

Question 13

What organs are affected by progressive accumulation of toxic molecules in lysosomal storage diseases?

Answer 13

bones, joints, liver, spleen, brain, craniofacial

Question 14

What metabolic condition is said to present with a “doll-like” appearance?

Answer 14

GSD1

Question 15

What are common symptoms for Fabry disease?

Answer 15

pain in extremities, sweating abnormalities, angiokeratomas, renal and cardiac issues later in life

Question 16

What are common symptoms for Gaucher disease?

Answer 16

bone pain, spleen and liver enlargement, anemia and thrombocytopenia

Question 17

What is the % enzyme activity for infantile onset Tay Sachs disease vs juvenile or adult onset?

Answer 17

0-5% enzyme activity vs 5-15%

Question 18

What does HEXA deficiency cause?

Answer 18

GM2 ganglioside accumulation –> Tay Sachs disease

Question 19

What percent of enzyme activity (in general) is enough to avoid symptoms of an associated biochemical disorder?

Answer 19

10%

Question 20

What is excreted in excess in the urine of individuals with mucopolysaccharidoses?

Answer 20

glycosaminoglycans

Question 21

What deficiency looks like methylmalonic aciduria?

Answer 21

vitamin B12/ cobalmin

Question 22

What deficiency looks like homocystinuria?

Answer 22

folic acid or vitamin B12

Question 23

What is a non-genetic cause of hyperammonia at birth?

Answer 23

neonatal asphyxia

Question 24

What are signs of a urea cycle disorder in a newborn?

Answer 24

acute and severe hyper ammonia, tachypnea, vomiting, lethargy, normal blood pH

Question 25

What are signs of an organic acidemia in a newborn?

Answer 25

acute sever ketoacidosis (low pH), vomiting, hyperpnea, lethargy

Question 26

What are symptoms of untreated galactosemia?

Answer 26

liver failure, feeding issues, jaundice, sepsis, vomiting, E coli

Question 27

What are signs of congenital adrenal hyperplasia in a newborn?

Answer 27

fasting intolerance, hypoglycemia, poor response to metabolic stress, salt wasting: low sodium high potassium, virilization in females, poor response to ACTH stimulation test

Question 28

Which MPS is XL?

Answer 28

MPS2- Hunter

Question 29

What are common symptoms of
Pompe disease?

Answer 29

GSD2 and LSD!
weakness, hypotonia, cardiomegaly, elevated CK, abnormal EKG, no hypoglycemia or liver involvement

Question 30

What are distinct characteristics of the mito genome?

Answer 30

small-37 genes
no introns
circular
no homologous recombination or meiosis
continuous replication
high mutation rate

Question 31

What are the varying recurrence risks for mito disease?

Answer 31

full sibling- 1-4% if mother not symptomatic
50% if mother symptomatic

up to 50% if offspring of affected

Question 32

What are red-flag symptoms for mito disease?

Answer 32

stroke like lesions without vascular pattern, basal ganglia affected, encephalopathy, epilepsy, myoclonus, ataxia, cardiomyopathy, WPW, retinal degeneration, GI, liver failure, hypotonia, FTT, acidosis, exercise intolerence, anesthesia hypersensitivity

Question 33

What is the most common mutation for LHON?

Answer 33

m.11778G>A

Question 34

What does MELAS stand for?

Answer 34

mitochondrial encephalopathy, lactic acidosis, stroke like symptoms

Question 35

What is the polymerase for the mito genome?

Answer 35

POLG

Question 36

What metabolic disease is characterized by bony stippling?

Answer 36

Zellwegger spectrum
PEX1 most common gene

Question 37

What skin finding is associated with Fabry disease?

Answer 37

angiokeratomas

Question 38

What is the typical onset/timing for Leigh syndrome?

Answer 38

3-12 months of age, following a viral infection

Question 39

What does MELAS stand for, and what is the most common causative mutation?

Answer 39

Mitochondrial encephalopathy, lactic acidosis, stroke like episodes

m.3243A>G MT-TL1

Question 40

What is MERRF?

Answer 40

myoclonic epilepsy associated with ragged red fibers
90% variants in MT-TK