Inborn Errors of Metabolism

Question 1

The disorder _____ is due to a defect in the breakdown of phenylalanine. What enzyme is effected?

Answer 1

PKU

Enzyme: Phenylalanine hydroxylase

Question 2

PKU symptoms?

Answer 2

Microcephaly, behavioral issues, tyrosine deficiency (hypopigmentation)

Question 3

What disease results from a defect in the metabolism of branched chain amino acids (Leu, Ile, Val)? What enzyme is deficient?

Answer 3

Maple Syrup Urine Disease (MSUD)

Enzyme: Branched chain ketoacid dehydrogenase

Question 4

MSUD Symptoms?

Answer 4

Poor feeding, maple syrup scented urine, ketoacidosis

Question 5

What disease results from a defect in the cleavage of glycine, is autosomal recessive, and has symptoms of hypotonia/encephalopathy and hiccuping/seizures in utero? What options are available for treatment?

Answer 5

Nonketotic hyperglycinemia

Tx: Benzoate, Dextramethorphan. DIETARY RESTRICTIONS INEFFECTIVE!

Question 6

In nonketotic hyperglycinemia, glycine is found in high concentration in the _____

Answer 6

CSF

Question 7

_____ is a disease caused by a defect in methionine and homocysteine metabolism. What enzyme/vitamins may be defective?

Answer 7

Homocystinuria

Enzyme/Vitamin defects:

Cystathionine Synthase (Vit B6) –> Elevated methionine

Folic Acid or B12 –> Low methionine

Question 8

What disease is characterized by symptoms similar to Marfan’s syndrome (tall stature, long fingers, pectus excavatum, ectopic lens)?

Answer 8

Homocystinuria

Question 9

The main issue in disorders of the urea cycle is _____.

Answer 9

Hyperammonemia

Question 10

The most common urea cycle disorder is _____. What is its pattern of inheritance? How is it treated?

Answer 10

Ornithine Transcabamylase Deficiency (OTD)

X-linked

Tx: Low protein diet, hemodialysis (if severe), liver transplant

Question 11

Ornithine Transcarbamylase Deficiency yields low levels of _____ and an excess of _____ and _____.

Answer 11

Low: Citrulline

Excess: Pyrimidines & Orotic acid (from carbamoyl phosphate)

Question 12

_____ are diseases caused by defects in the conversion of amino acid catabolism intermediates into Kreb Cycle compounds like acetyl CoA and succinyl CoA. What are some features of these diseases?

Answer 12

Organic Acidemias

Features: Increased anion gap, metabolic acidemia, organic aciduria, elevated ammonia, secondary carnitine deficiency

Question 13

_____ is caused by a blockage in the conversion of propionyl CoA to methylmalonyl CoA. What is the cofactor needed for the deficient enzyme?

Answer 13

Propionic acidemia.

Cofactor: Biotin

Question 14

_____ is caused by an inability to convert methylmalonyl CoA to succinyl CoA. What is the cofactor for the deficient enzyme? How can we treat this disease?

Answer 14

Methylmalonic acidemia

Cofactor: B12

Tx: B12 shots, carnitine to remove organic acids

Question 15

_____ is caused by a defect in the metabolism of glutaryl CoA to crotonyl CoA before conversion to acetyl CoA, and is associated with movement disorders. What are some treatment options for this disease?

Answer 15

Glutaric Acidemia Type I

Tx: Diet restriction of lysine and leucine, carnitine/riboflavin supplements

Question 16

_____ is the most common fatty acid oxidation disorder. It is asymptomatic until fasting, at which point the patient will display hypoglycemia and _____.

Answer 16

Medium Chain Acyl CoA Dehydrogenase Defect (MCAD)

When fasting, patients will show hypoketosis and hypoglycemia.

Question 17

A patient is brought to the ER by his wife (hehe). His wife explains that he fainted at home, and he has not eaten in 24 hours. He is hypoglycemic, and has no ketones in the urine. What kind of metabolic disorder is he most likely to have?

Answer 17

Disorder of fatty acid oxidation

Question 18

_____ is a disorder that has symptoms including cardiomyopathy, irritability, failure to thrive, hypotonia, and hypoglycemia with inappropriately low levels of ketones, metabolic acidosis.

Answer 18

Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD)

Question 19

Diagnosis of fatty acid oxidation disorders is accomplished through _____

Answer 19

You being really fucking smart.

Also acylcarnitine analysis.

Question 20

Treatment for disorders of fatty acid oxidation are _____ and _____

Answer 20

Avoidance of fasting and low fat diet

Question 21

In classic galactosemia what enzyme is deficient?

Answer 21

Galactose I phosphate uridyltransferase

Question 22

A deficiency of glactose-1-phosphate uridyltransferase, cataracts, liver disease, jaundice, renal tubular disease, and acidosis without anion gap are all signs of _____

Answer 22

Classic Galactosemia

Question 23

What enzyme is deficient in Hereditary Fructose Intolerance?

Answer 23

Alsolase B

Question 24

Patients with Hereditary Fructose Intolerance cannot absorb fructose and therefore are susceptible to _____

Answer 24

Hypoglycemia

Question 25

Von Gierke Disease Ia is a deficiency of _____. What symptoms do patients with the typical presentation of this disease exhibit?

Answer 25

Glucose-6-phosphatease

Symptoms: Hepatomegaly, lactic acidosis, hyperuricemia (gout), hyperlipidemia

Question 26

_____ is a deficiency of glucose 6 phosphate translocase. What’s the problem in this disease? What is a unique feature of this disease?

Answer 26

Von Gierke Disease Type Ib

Problem: Glucose-6-P can’t be transported into ER > Can’t be dephosphorylated to free glucose.

Unique feature: Neutropenia (abnormally low neutrophils)

Question 27

A deficiency in the lysosomal alpha glucosidase (problem with glycogen breakdown) is known as _____ disease. A typical presentation of this disease includes what symptoms?

Answer 27

Pompei Disease.

Symptoms: Abnormal EKG, muscle weakness

Question 28

A deficiency in the glycogen debranching enzyme is known as _____.

Answer 28

Cori Disease (Debrancher deficiency - GSD III)

Question 29

An absence of the glycogen branching enzyme is known as _____. The prognosis for this disease is _____.

Answer 29

Brancher Deficiency - GSD IV

Prognosis: Not so good. Usually fatal, but a liver transplant may help.

Question 30

McArdle Disease (GSD V) is a deficiency in _____. What is the typical presentation?

Answer 30

Muscle glycogen phosphorylase deficiency

Typical presentation: Teenagers or older with weakness and cramping after moderate exercise. May also present with myoglobinemia, myoglobinuria or rhabdomyolysis.

Question 31

The major feature of lysosomal storage diseases is _____

Answer 31

Developmental regression (loss of language skills, motor skills, etc.)

Question 32

_____ result from the buildup of GAG products

Answer 32

Mucopolysaccharidoses

Question 33

Hurler’s Syndrome is a deficiency in _____.

Answer 33

Alpha L-iduronidase

Question 34

A child is brought to your clinic after his mother noticed a decline in his intellect and motor coordination. You notice his eyebrows are especially thick, he has corneal clouding. Physical exam reveals hepatosplenomegaly, and a dysostosis multiplex (thick ribs, flared pelvis, short/thick long bones). What disease do you suspect this child has?

Answer 34

Hurler’s Syndrome

Question 35

Patients with _____ Syndrome have similar symptoms to those with Hurler’s Syndrome (Corneal clouding, distinct facial features, short stature, broad ribs, slight regression in learning skills etc etc). Patients with this syndrome develop symptoms later in life than those with Hurler’s.

Answer 35

Hurler-Scheie Syndrome

Question 36

Hunter’s Syndrome is a deficiency in the enzyme _____

Answer 36

Iduronate Sulfatase

Question 37

Patients with Hunter’s Syndrome have very similar symptoms to patients with Hurler’s Syndrome (and a syndrome with a very similar name!). What distinguishes Hunter’s from Hurler’s?

Answer 37

NO corneal clouding in Hunter’s

Hunter's = X-linked
Hurler's = Autosomal Recessive

Question 38

Patients with _____ have a problem with heparan sulfate metabolism, mild physical manifestations, and severe behavioral/neurological features. Patients are essentially normal for the first five years of life, then decline.

Answer 38

Sanfilipo Syndrome

Question 39

Patients with Morquio Syndrome have problems with keratin sulfate metabolism. What are some symptoms of this disease?

Answer 39

Joint laxity, short stature, skeletal deformities, odontoid hypoplasia, genu valgum (knock kneed)

Question 40

What is deficient in Maroteaux-Lamy?

Answer 40

Arylsulfatase B

Question 41

What syndrome presents similarly to Hurler’s Syndrome with the exception that the CNS is relatively spared?

Answer 41

Maroteaux-Lamy Syndrome

Patients have short stature, mitral valve prolapse, genu valgum (knock kneed), arylsulfatase B deficieny

Question 42

What enzyme is deficient in Niemann-Pick disease?

Answer 42

Sphingomyelinase

Question 43

Your patient Jacques Boudreaux, a three month old Acadian boy, is in your office. You notice that when you close the exam room door behind you, Jacques is extremely startled. Your physical exam prowess comes to the fore, revealing a cherry red macula, hypotonia, and motor weakness. His liver is within normal limits. What disease do you suspect lil’ Jacques has? What enzyme is deficient in this disease?

Answer 43

Tay-Sachs

Enzyme: Hexosaminidase A

Question 44

What disease presents similarly to Tay-Sachs with the addition of hepatosplenomegaly w/ascites?

Answer 44

GM1 Gandliosidosis

Question 45

A lysosomal accumulation of sulfatides is caused by what disease? What is the course of this disease?

Answer 45

Metachromatic Leukodystrophy

Course: Patient develops normally for a year followed by a rapid loss of cognitive, motor and eventually respiratory functions.

Question 46

What enzyme is deficient in Smith-Lemli-Opitz Syndrome? What is the result of this deficiency?

Answer 46

Enzyme: 7-dehydrocholesterol reductase

Result: Very low cholesterol levels

Question 47

A big giveaway for Smith-Lemli-Opitz Syndrome is _____

Answer 47

Polydactyly!