Enzyme Deficiencies

Question 1

Pompe disease

Answer 1

Def: acid alpha glucosidase
Can’t break down glycogen properly
AR. muscle weakness, cardiomyopathy, hepatomegaly.
Treatment: Gene or enzyme therapy

Question 2

Galactosemia

Answer 2

Def: Galactose 1-p uridyltransferase (converts galactose 1-p to UDP-galactose)
Accumulation of galactose which is toxic to tissues. Diarrhea, vomiting, jaundice
AR
Treatment: Galactose free diet supplement with vit. D and calcium.

Question 3

Hereditary Fructose Intolerance

Answer 3

Def: Aldolase B (convert fructose 1-p to Glyceraldehyde 3 phosphate and dihydroxyacetone P)
A part of glycolysis
AR. Accumulation of fructose 1-p and so hypoglycemia, jaundice, hepatomegaly, vomitting
Treatment: low fructose diet

Question 4

Glucose-6-phosphate Dehydrogenase Deficiency

Answer 4

Def: G-6-p Dehydrogenase
(converts G-6-P to 6-phosphoglucano delta lactone)
a part of pentose phosphate pathway
X-linked Recessive (more males get it). Oxidative stress causes burst in RBCs, anemia, jaundice
Treatment: Avoid fava beans, oxidative agents like drugs. Blood transfusion

Question 5

Medium chain Acyl Coa Dehydrogenase Deficiency

Answer 5

Def: Medium chain Acyl coa Dehydrogenase Deficiency
(converts fatty acids and coenzyme A to acyl CoA) a part of beta oxidation.
AR. Can’t break down medium chain FA so hepatomegaly, no gluconeogenesis
Treatment: glucose or simple sugars

Question 6

Zellweger Syndrome

Answer 6

Issue: No peroxisomes. Myelin can’t break down in the CNS so accumulation of VLFA
AR. Seizure. Loss of vision, sensation. poor feeding. developmental delay
Has infantile, childhood and adolescent forms. Worst is in childhood.
Treatment: Treatment of symptoms. MRI of the brain, liver function, monitor cognitive and motor function.

Question 7

Tay-Sachs disease

Answer 7

Def: beta-N-acetylhexaminidase A
Break down of sphingolipids is messed up. Accumulation of gangliosides. More common in Jews and French Canadians.
AR
Motor dysfunction and hearing loss

Question 8

Gaucher disease

Answer 8

Def: glucocerebrosidase
AR
Issues with platelets like bruising easy, anemia, hepatomegaly, neurological complications.
Treatment: gene therapy

Question 9

Fabry disease

Answer 9

Def: alpha galactosidase A
XR (more males get it )
Pain in the hands and feet. Angiokeratomas, decreased sweating. Kidney issues.
Treatment: pain management, ACE inhibitors for proteinuria, renal transplant

Question 10

Hurler syndrome( MPS I)

Answer 10

Def: alpha-L-iduronidase
AR. Problem with breaking down glycosaminoglycans in the lysosome. They build up in organs. Large birth weights, hernia, microcephalic, hydrocephaly, intellectual disability.

Treatment: sunglasses to reduce glare or correction surgery.

Question 11

I-cell Disease (ML II)

Answer 11

Def: N-acetyl glucosamine-1-p transferase
aka inclusion cell disease
AR- developmental delay, skeletal abnormalities, restricted joint movement, enlarged organs.
Treat the symptoms and give iron and B12

Question 12

Lesch-Nyhan Syndrome (LNS)

Answer 12

Def: HGPRT
so salvaging hypoxanthine and guanine
XR- (more males get it)
self harm, neurological dysfunction, hematuria, sand llike crystals in diaper, juvenile gout, uric acid build up and kidney stones
Treatment: Allopurinol for gout, lithotripsy for kidney stones

Question 13

Acute intermittent Porphyria

Answer 13

Def: prophobilinogen deaminase (aka hydroxymethylbilane synthase).
AD. abdominal pain, neuropsyc issues, dark urine
Treatment: high carbs, opiates for pain.

Question 14

Gilbert Syndrome

Answer 14

Def: bilirubin uridine diphosphate glucuronosyltransferase
AR. increased unconjugated bilirubin. jaundice that happens with stress (dehydration, fasting, illness, crazy exercise, menstruation)

Question 15

Crigler-Najjar Syndrome Type I

Answer 15

Def: Complete absence of the enzyme (bilirubin uridine diphosphate glucuronosyltransferase)
AR. increased unconjugated bilirubin
jaundice with stress (dehydration, fasting, illness, crazy exercise, menstruation)
Treatment: phototherapy, exchange transfusion, liver transplantation

Question 16

Crigler-Najjar Syndrome Type II

Answer 16

Def: Partial absence of the enzyme (bilirubin uridine diphosphate glucuronosyltransferase)
similar to Gilbert Syndrome.
AD. increased unconjugated bilirubin. Jaundice with stress (dehydration, fasting, illness, crazy exercise, menstruation)
Treatment: Phenobarbital

Question 17

Dubin-Johnson Syndrome

Answer 17

Def: Multidruug resistant protein 2
AR. Issue with transfering bilirubin out of the liver. more common in Iranians,and Morocon jews
Jaundice due to conjugated bilirubin build up, dark liver
Treatment: nothing necessary.

Question 18

Rotor Syndrome

Answer 18

Def: Solute carrier organic anion transporter
AR. Issue with transferring the bilirubin out of the liver
Jaundice to to conjugated bilirubin.
Treatment: no treatment necessary

Question 19

PKU

Answer 19

Def: phenylalanine hydroxylase (converts phenylalanine to tyrosine)
AR. Dark urine, musty smell, intellectual disabilities.
Treatment: Tyrosine supplement, low protein diet.

Question 20

ornithine transcarbamylase deficiency

Answer 20

Def: ornithine transcarbamylase (converts ornithine to citrulline)
X-linke R. This is the beginning of the urea cycle so ammonia build up and its toxic for the brain. Seizures, neuropsyc issues.
Treatment: Arginine supplement, sodium benzoate to scaveneg nitrogen

Question 21

Tyrosinemia I

Answer 21

Def: fumaryacetoacetate hydroxylase (breaks down tyrosine)
AR. Tyrosine builds up which is toxic for the liver. Rancid butter/cabbage smell of urine
Treatment: low tyrosine diet

Question 22

Alkaptonuria

Answer 22

Def: homogentisate 1,2-dioxidase
AR. Can’t break down tyrosine. pain in joints, black cartilage and black urine. excess homogentisitic acid turns into benzoquinone acetic acid which deposits into the collagen making it black and stiff.
Treat: low tyrosine and phenylalanine dier. joint replacement

Question 23

Homocystinuria

Answer 23

Def: CBS (cystathionine beta-synthase which converts homocystein and serine into cysteine)
AR. homocystein and methionine in the urine. myopia, dislocation of the lens, brittle bones, abnormal blood clots
Treat: pyridoxine and folic acid.

Question 24

Maple syrup urine

Answer 24

Issue is breaking down branched AA
AR. Build up of branched AA which is toxic to the brain, maple syrup smell of the urine and ear wax
Treat: Avoid branched AA in diet (valine, leucine and isoleucine)

Question 25

Cystinuria

Answer 25

issue is with neutral and basic AA getting transported across the epithelia of the kidneys.
AR. persistent kidney stones, pink to yellow turning of the stones
Treatment: urine alkalization and chelation therapy

Question 26

Hartnup disease

Answer 26

Def: sodium dependent neutral AA transporter
transports the AA across the kidneys epithelia.
AR. deficiency in niacin and tryptophan. Pellagra (dermatitis, diarrhea, death)
Treatment: high protein diet

Question 27

Glycogen Storage Disease

Answer 27

def: glycogen synthase (adds glucose to glycogen)
AR. hypoglycemia or seizures b4 breakfast bc no glycogen can be created and stored in th eliver.
treatment: small meals with carbs.

Question 28

Von Gierke Disease

Answer 28

Def: Glucose 6-phosphatase (removes p from glucose. Converts glucose 6-p to glucose)
AR. enlarged liver
Treatment: frequent small meals with carbs (cornstarch)

Question 29

McArdle disease

Answer 29

Def: Glycogen phosphorylase (removes one glucose from glycogen)
AR. muscle cramps during exercise bc glucose can not be released from the muscle.
Treatment: sucrose 30 mins prior to working out.