Student Metabolic Presentations

Question 1

What gene is implicated in Menkes syndrome?

Answer 1

ATP7A

Question 2

What is the biochemical consequence of Menkes syndrome?

Answer 2

poor distribution of copper throughout the body, resulting in toxic accumulation levels in kidneys and small intestine and unusually low levels in tissues like the brain

Question 3

What is the inheritance of Menkes syndrome?

Answer 3

X-linked dominant

Question 4

What are clinical symptoms associated with Menkes syndrome?

Answer 4

hypothermia, hypoglycemia, prolonged jaundice, sparse kinky hair, FTT, and CNS deterioration

Question 5

What is the treatment for Menkes syndrome?

Answer 5

daily subcutaneous copper histidinate injections to improve neurodevelopmental outcomes

Question 6

What gene is implicated in Wilson disease?

Answer 6

ATP7B

Question 7

What is the inheritance pattern of Wilson disease?

Answer 7

autosomal recessive

Question 8

What are the clinical symptoms of Wilson disease?

Answer 8

liver disease, neurologic disease, psychiatric disturbance, and some hemolytic anemia

Question 9

What is the characteristic eye finding in Wilson disease?

Answer 9

Kayser-Fleisher rings: golden, brown, or green coloration of the cornea due to copper accumulation

Question 10

What is the onset of Wilson disease?

Answer 10

Typically between 6 and 45yo

Question 11

What is the treatment for Wilson disease?

Answer 11

Chelation therapy and zinc salts to bind to copper and remove it from the body
liver transplantation recommended for acute liver failure or decompensated liver cirrhosis

Question 12

What is the gene associated with Smith-Lemli-Opitz syndrome?

Answer 12

DHCR7

Question 13

What is the inheritance pattern of SLOS?

Answer 13

Autosomal recessive

Question 14

What are the clinical symptoms associated with SLOS?

Answer 14

growth restriction/short stature
microcephaly
ID
behavioral concerns

Question 15

What is the etiology of SLOS?

Answer 15

7-dehydrocholesterol reductase enzyme deficiency (last step of cholesterol biosynthesis), leading to generalized cholesterol deficiency

Question 16

What is the treatment for SLOS?

Answer 16

cholesterol supplementation in diet

Question 17

What is the gene implicated in biotinidase deficiency?

Answer 17

BTD

Question 18

What is the inheritance pattern in biotinidase deficiency?

Answer 18

autosomal recessive

Question 19

What are the two types of biotinidase deficiency?

Answer 19

profound: <10% enzyme activity
partial: 10-30% enzyme activity

Question 20

What is the onset for each type of biotinidase deficiency?

Answer 20

profound: avg 3.5 mos
partial: can be later and may only be symptomatic when stressed

Question 21

What are the clinical symptoms of biotinidase deficiency?

Answer 21

neurological: ataxia, seizures, hypotonia, SNHL, vision problems
cutaneous: eczematous skin rash, alopecia
immunological: conjunctivitis, candidiasis

Question 22

What are the biochemical impacts of biotinidase deficiency?

Answer 22

body is unable to recycle/synthesize biotin

Question 23

What is the treatment for biotinidase deficiency?

Answer 23

take biotin supplements and avoid eating raw eggs (protein in albumin binds biotin and reduces its bioavailability)

Question 24

What are porphyrins?

Answer 24

a group of compounds that are essential for hemoglobin to bind iron and transport oxygen

Question 25

What is the gene implicated in acute intermittent porphyria?

Answer 25

HMBS

Question 26

What is the enzyme implicated in acute intermittent porphyria?

Answer 26

porphobilinogen deaminase (PBGD)

Question 27

What is the inheritance pattern of acute intermittent porphyria?

Answer 27

autosomal dominant

Question 28

True or false: acute intermittent porphyria is completely penetrant

Answer 28

False! exogenous or endogenous trigger is required for acute attack to occur

Question 29

what is the age of onset of acute intermittent porphyria?

Answer 29

20s/30s

Question 30

What clinical symptoms are associated with acute intermittent porphyria attacks?

Answer 30

severe abdominal pain, GI symptoms like nausea and vomiting, neurological symptoms like peripheral neuropathy, psychological symptoms like irritability and depression, cardiovascular symptoms like tachycardia and hypertension, hyponatremia contributing to seizures

Question 31

What are chronic complications of acute intermittent porphyria?

Answer 31

hypertension, hepatocellular carcinoma, progressive renal dysfunctional and renal failure, chronic pain

Question 32

What is the testing strategy for acute intermittent porphyria?

Answer 32

biochemical test for PBGD in urine
genetic testing is not considered frontline testing due to incomplete penetrance and variable expressivity

Question 33

What is the treatment during an acute attack related to AIP?

Answer 33

treat with enzyme inhibitor, manage severe pain, monitor fluid/electrolyte levels

Question 34

How can AIP attacks be prevented?

Answer 34

maintain a balanced diet, avoid drugs that exacerbate porphyria, limit alcohol and drug use, promptly treat infections and illness, provide AFAB individuals with regular hematin infusion to reduce production or porphyrin precursors

Question 35

What genes are implicated in propionic acidemia?

Answer 35

PCCA or PCCB

Question 36

What enzyme is implicated in propionic acidemia?

Answer 36

propionyl-CoA carboxylase (PCC)

Question 37

What are the biochemical impacts of propionic acidemia?

Answer 37

accumulation of propionic acid results in persistent metabolic acidosis
also a buildup of fat and cholesterol

Question 38

What are the clinical symptoms of propionic acidemia?

Answer 38

poor feeding, vomiting, lethargy, hypotonia, and irritability which can progress to encephalopathy, seizures, coma, respiratory failure, and death

Question 39

What is the onset of propionic acidemia?

Answer 39

Typically neonatal but there is a late-onset form in which symptoms appear after a crisis (like infection, fasting, or surgery)