Question 1

Which of the following best describes the threshold effect in mitochondrial DNA (mtDNA) disorders?

Accepted Answer

A critical proportion of mutated mtDNA must be exceeded before a biochemical abnormality is expressed.

Question 2

A woman with a heteroplasmic mtDNA mutation has three children. Which statement best describes the risk and clinical expression in her offspring?

Accepted Answer

Each child may inherit a different proportion of mutated mtDNA, leading to variable clinical manifestations.

Question 3

Which clinical feature is most commonly associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes)?

Accepted Answer

Stroke-like episodes before age 40

Question 4

A family history reveals males and females affected in multiple generations, with affected females transmitting the disorder to all their children, but affected males not transmitting it. What is the most likely mode of inheritance?

Accepted Answer

Mitochondrial (maternal) inheritance

Question 5

Which of the following genes is encoded by mitochondrial DNA (mtDNA) and not by nuclear DNA (nDNA)?

Accepted Answer

ND1

Question 6

A patient presents with external ophthalmoplegia, bilateral ptosis, and mild proximal myopathy. Which mitochondrial syndrome is most likely?

Accepted Answer

Chronic progressive external ophthalmoplegia (CPEO)

Question 7

Which laboratory finding would most strongly support a diagnosis of a mitochondrial disorder in a patient with neurologic symptoms?

Accepted Answer

Fasting blood lactate concentration above 3 mmol/L

Question 8

Which of the following statements about the inheritance of nuclear DNA (nDNA) mitochondrial disorders is correct?

Accepted Answer

They may be inherited in autosomal recessive, autosomal dominant, or X-linked patterns.

Question 9

A muscle biopsy from a patient with suspected mitochondrial disease shows ragged-red fibers. This finding is most commonly associated with which syndrome?

Accepted Answer

MELAS

Question 10

Which of the following best explains why clinical manifestations of mtDNA disorders can vary widely among siblings?

Accepted Answer

Random segregation of mutated mtDNA during oogenesis leads to different proportions of mutated mtDNA in each child.

Question 11

A patient with a mitochondrial disorder is found to have a large-scale mtDNA deletion. What is the most likely recurrence risk for siblings if the deletion occurred de novo?

Accepted Answer

$$\frac{1}{24}$$

Question 12

Which of the following is a key reason why molecular genetic testing of blood may fail to detect a pathogenic mtDNA variant in a patient with a mitochondrial disorder?

Accepted Answer

Heteroplasmy levels may be lower in blood than in affected tissues.

Question 13

A patient with subacute painless bilateral visual failure, with a male:female ratio of 4:1 and median onset at 24 years, most likely has which mitochondrial disorder?

Accepted Answer

LHON (Leber hereditary optic neuropathy)

Question 14

Which of the following is TRUE regarding the D-loop region of the mitochondrial genome?

Accepted Answer

It is a noncoding region involved in regulation of transcription and replication.

Question 15

A patient with a mitochondrial disorder is found to have a mutation in a nuclear gene encoding a respiratory chain assembly factor. Which of the following clinical presentations is most likely?

Accepted Answer

Encephalopathy, liver failure, and renal tubulopathy

Question 16

Which of the following best describes the inheritance risk for the offspring of a male with a pathogenic mtDNA variant?

Accepted Answer

None of his offspring will inherit the variant.

Question 17

Which of the following is a recommended first-line laboratory test for a patient with suspected mitochondrial myopathy?

Accepted Answer

Plasma lactate concentration

Question 18

Which of the following statements about the clinical management of mitochondrial disease is correct?

Accepted Answer

There are currently no treatments known to influence the disease course.

Question 19

A patient with a mitochondrial disorder is found to have a mutation in the POLG gene. Which of the following statements is most accurate?

Accepted Answer

POLG mutations can cause a spectrum of overlapping disease phenotypes.

Question 20

Which of the following is a distinguishing feature of Pearson syndrome?

Accepted Answer

Sideroblastic anemia of childhood and exocrine pancreatic failure

Primary Mitochondrial Disorders: Genetic Basis, Clinical Features, and Diagnostic Strategies

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