Question 1

Which of the following may be associated with hyperphenylalaninemia that is refractory to management of dietary phenylalanine?&#10;A) Tetrahydrobiopterin deficiency&#10;B) Complete loss of phenylalanine hydroxylase activity&#10;C) Dominant negative mutation in phenylalanine hydroxylase&#10;D) Maternal PKU&#10;E) Deficiency in phenylalanine uptake

Accepted Answer

Hyperphenylalaninemia that is refractory to dietary management is often seen in individuals with tetrahydrobiopterin deficiency, which leads to reduced activity of phenylalanine hydroxylase. This deficiency can be caused by mutations in the genes encoding enzymes involved in the biosynthesis, recycling, or regeneration of tetrahydrobiopterin.

Question 2

Individuals with defects in the biogenesis for this organelle have defects in fatty acid oxidation and biosynthesis of certain phospholipids.&#10;A) Lysosome&#10;B) Peroxisome&#10;C) Mitochondria&#10;D) Nucleus&#10;E) Golgi apparatus

Accepted Answer

Defects in peroxisome biogenesis have been linked to defects in fatty acid oxidation and the biosynthesis of certain phospholipids. The peroxisome is responsible for the breakdown of fatty acids and the synthesis of certain lipids, including plasmalogens, which are important for brain function. Therefore, defects in peroxisome biogenesis can lead to a number of disorders, including Zellweger syndrome and X-linked adrenoleukodystrophy.

Question 3

What is the primary defect causing familial hypercholesterolemia?&#10;A) Defective or deficient LDL receptors&#10;B) Defective HMG-CoA reductase&#10;C) Deficiency of acyltransferase&#10;D) Deficiency of phospholipase C&#10;E) Deficiency of hexosaminidase A

Accepted Answer

Familial hypercholesterolemia is caused by a genetic defect that leads to either defective or deficient LDL receptors on the surface of cells. This results in decreased uptake of LDL from the bloodstream and elevated levels of circulating cholesterol, which can lead to increased risk of cardiovascular disease. Defective HMG-CoA reductase, deficiency of acyltransferase, deficiency of phospholipase C, and deficiency of hexosaminidase A are not primary defects that cause familial hypercholesterolemia.

Question 4

What modification has increased the success of enzyme replacement therapy for Gaucher disease?&#10;A) Using larger doses of enzyme&#10;B) Targeting the enzyme to cross the blood-brain barrier&#10;C) Modifying the enzyme so that it is targeted to macrophage lysosomes&#10;D) Providing the enzyme in conjunction with a bone marrow transplant&#10;E) Removal of the spleen before treatment

Accepted Answer

Modifying the enzyme so that it is targeted to macrophage lysosomes has increased the success of enzyme replacement therapy for Gaucher disease. This is because Gaucher disease is caused by the deficiency of beta-glucocerebrosidase in macrophage lysosomes, so targeting the replacement enzyme to these specific locations increases its effectiveness.

Question 5

Deficiency for what enzyme is the most common cause of female genital virilization?&#10;A) 11b-hydroxylase&#10;B) Desmolase&#10;C) 3b-hydroxysteroid dehydrogenase&#10;D) 5a-reductase&#10;E) 21-hydroxylase

Accepted Answer

21-hydroxylase deficiency is the most common cause of female genital virilization. This enzyme is responsible for the production of cortisol and aldosterone, as well as androgens, in the adrenal gland. When there is a deficiency in 21-hydroxylase, there is an accumulation of androgens that can lead to virilization of the female genitalia.

Question 6

For which of the following disorders would prenatal genetic diagnosis be particularly difficult?&#10;A) Cystic fibrosis&#10;B) Down syndrome&#10;C) Lesch-Nyhan syndrome&#10;D) MERRF&#10;E) Tay-Sachs disease

Accepted Answer

MERRF (Myoclonic Epilepsy with Ragged Red Fibers) is caused by mutations in mitochondrial DNA, which can vary greatly in their distribution among cells (heteroplasmy). This variability makes prenatal diagnosis particularly challenging, as the mutation load in sampled tissues (like chorionic villi or amniocytes) may not accurately reflect the mutation load in the fetus overall.

Question 7

What pattern of inheritance is most often associated with disorders of mitochondrial function?&#10;A) Autosomal dominant&#10;B) Autosomal recessive&#10;C) Maternal inheritance&#10;D) X-linked dominant&#10;E) X-linked recessive

Accepted Answer

The answer of What pattern of inheritance is most often...

Question 8

How does MCAD deficiency usually present?&#10;A) In adulthood, with myopathy&#10;B) In early childhood, after an illness that leads to fasting&#10;C) In childhood, with progressive vision loss&#10;D) In early adulthood, with a thrombotic event&#10;E) Any of the above

Accepted Answer

MCAD deficiency typically presents in early childhood, after an illness or period of fasting, with symptoms such as vomiting, lethargy, and hypoglycemia. If left untreated, it can lead to liver failure and even death in severe cases. Other symptoms may include seizures, encephalopathy, and cardiomyopathy. However, some individuals with MCAD deficiency may remain asymptomatic throughout their lives, while others may present with symptoms such as myopathy or thrombotic events in adulthood. Vision loss is not typically associated with MCAD deficiency.

Question 9

Reduced melanin production in individuals with phenylketonuria is a result of deficiency for which of the following?&#10;A) Phenylalanine&#10;B) Tyrosine&#10;C) Thyroxine&#10;D) Acetoacetic acid&#10;E) Ketones

Accepted Answer

Tyrosine is a precursor for melanin production, and individuals with phenylketonuria have deficient phenylalanine hydroxylase activity, leading to decreased conversion of phenylalanine to tyrosine. Therefore, reduced melanin production in individuals with phenylketonuria is a result of the deficiency of tyrosine, not phenylalanine, thyroxine, acetoacetic acid, or ketones.

Deck 11: Biochemical Genetics