Inborn Errors of Metabolism (IEMs)

A defect in the BC enzyme in inborn errors of metabolism leads to which of the following?

Which of the following is NOT a major category of inborn errors of metabolism?

In inherited metabolic disorders, symptoms may be triggered by which of the following?

A 22-year-old female, G3P2, presents for a dating ultrasound, which is consistent with an 11-week, 5-day intrauterine pregnancy. She has two sons, one of whom has phenylketonuria (PKU). What is the MOST important counseling point?

What is the inheritance pattern of phenylketonuria (PKU)?

Which dietary modification is MOST appropriate for managing classic phenylketonuria (PKU)?

An 8-year-old female presents with difficulty seeing the blackboard, developmental delays, marfanoid habitus, myopia, bilateral ectopia lentis, mild intellectual disability, and pectus deformity. Lab results show elevated methionine and homocysteine. Which condition is MOST likely?

A defect in cystathionine beta-synthase (CBS) disrupts the conversion of homocysteine to cystathionine. This results in which of the following?

Why is homocysteine more problematic than methionine?

What is the INITIAL step in managing a newly diagnosed patient with homocystinuria?

What is a key dietary recommendation for patients with homocystinuria?

Deficiencies in which of the following vitamins can lead to hyperhomocysteinemia by impairing the conversion of homocysteine to methionine?

A 4-month-old female presents with irritability, abdominal distention, poor weight gain, constant hunger, and is 'fuzzy' between feedings. Physical exam reveals height and weight below the 5th percentile, hepatomegaly, thin limbs, and a 'doll-like' face with chubby cheeks. Labs show hypoglycemia, elevated LFTs, lactate, lipids, and uric acid. What condition is MOST likely?

A newborn screening test comes back as 'likely affected' but after confirmatory genetic testing, NO mutation is found. What is the next diagnostic step in this case?

Which enzyme is deficient in Glycogen Storage Disease Type 1a?

A child with Glycogen Storage Disease Type 1 (Von Gierke) requires frequent meals. What is something to be AVOIDED?

Which of the following medications is MOST likely to be prescribed for a patient with Glycogen Storage Disease Type 1 (Von Gierke) to manage hyperuricemia?

For a patient with Glycogen Storage Disease Type 1 (Von Gierke) experiencing an acute episode of hypoglycemia, which intervention is MOST appropriate?

What is the PRIMARY function of lysosomes?

A 7-month-old female presents with developmental regression, hypotonia, decreased responsiveness, visual impairment, and exaggerated startle responses. She is of Jewish ancestry. Fundoscopic exam reveals a cherry-red spot. Genetic testing is MOST likely to reveal pathogenic variants in which gene?

Tay-Sachs disease is caused by the deficiency of which enzyme?

The accumulation of which substance leads to the pathophysiology of Tay-Sachs disease?

Which population has the HIGHEST carrier frequency for the Tay-Sachs disease allele?

A 2-week-old male infant is brought to the ED due to lethargy and poor feeding. On exam, he shows signs of encephalopathy, hypotonia, and intermittent posturing. Labs reveal increased ammonium levels. Which condition is MOST likely?

Ornithine transcarbamylase (OTC) deficiency results in the disruption of which biochemical process?

An infant has hyperammonemia due to OTC deficiency. Why is a high ammonium concentration dangerous?

What is the inheritance pattern of Ornithine transcarbamylase deficiency (OTCD)?

A female presents with a long history of 'intolerance to protein'. She is planning to become pregnant. Which of the following genetic disorders is MOST likely?

If a patient with OTC deficiency has an ammonium level over 800 uM/L, what is the appropriate intervention?

A 16-month-old male infant presents with developmental regression, recurrent fevers, and difficulty feeding. Development was normal until 12 months, with a gradual loss of motor skills and speech. Exam reveals hypotonia, nystagmus, ataxia, and swallowing difficulty. Labs show elevated serum and CSF lactate levels. Which condition is MOST likely?

Leigh syndrome involves mutations in:

A distinctive feature of mitochondrial DNA inheritance is that it is inherited from:

What term describes the presence of multiple mitochondrial variants within a single cell or individual?

A 16-year-old male presents with progressive weight gain, hyperphagia, cognitive impairment, and incomplete secondary sexual characteristics. Exam: obese, small hands and feet, and micropenis. DNA testing reveals a paternal deletion at 15q11.2-q13. Which condition is MOST likely?

Prader-Willi syndrome is caused by the loss of function of which gene?

What genetic phenomenon underlies Prader-Willi syndrome and Angelman syndrome?

In genomic imprinting, if the paternal allele is imprinted, which allele is expressed?

Which of the following is a mechanism that results in genomic imprinting disorders like Prader-Willi and Angelman syndromes?

What does UBE3A expression in neurons depend on?

What is the most common test used to support the diagnosis of Prader-Willi Syndrome?

In inborn errors of metabolism (IEMs), what is the consequence of a defect in an enzyme?

What triggers symptoms in inherited metabolic disorders?

What counseling is MOST important for a 22-year-old female, G3P2, at 11 weeks 5 days gestation, who has two sons, one with PKU?

Which intervention is MOST appropriate for managing hyperuricemia in a patient with Glycogen Storage Disease Type 1 (Von Gierke)?

Which characteristic is associated with homocystinuria?

What dietary modification is essential for managing homocystinuria?

Deficiencies in which of the following vitamins can lead to hyperhomocysteinemia by impairing the conversion of homocysteine to cystathionine?

A 4-month-old female presents with irritability, abdominal distention, poor weight gain. Exam reveals hepatomegaly, thin limbs, and a 'doll-like' face. Labs show hypoglycemia, elevated LFTs, lactate, lipids, and uric acid. What is the MOST likely diagnosis?

What is a key dietary recommendation for patients with Glycogen Storage Disease Type 1 (Von Gierke)?

What imaging modality is MOST appropriate for detecting glycogen accumulation in the liver and measuring liver and kidney size in Glycogen Storage Disease Type 1 (Von Gierke)?

A 7-month-old female presents with developmental regression, hypotonia, decreased responsiveness, visual impairment, and an exaggerated startle response. Fundoscopic exam reveals a cherry-red spot. What condition is MOST likely?

Ornithine transcarbamylase (OTC) deficiency directly impairs which metabolic process?

A female presents with a long history of 'intolerance to protein'. Which genetic disorder is MOST likely?

A 16-month-old male infant presents with developmental regression, recurrent fevers, and difficulty feeding. Exam reveals hypotonia, nystagmus, ataxia, and swallowing difficulty. Labs show elevated serum and CSF lactate levels. Which condition is MOST likely?

In mitochondrial inheritance, maternally inherited mtDNA is due to.

A 16-year-old male presents with progressive weight gain, hyperphagia, cognitive impairment, and incomplete secondary sexual characteristics. Exam reveals obesity, small hands and feet, and micropenis. DNA testing reveals a paternal deletion at 15q11.2-q13. Which condition is MOST likely?

What genetic mechanisms can result in genomic imprinting disorders like Prader-Willi and Angelman syndromes?

If the maternal allele is imprinted, which allele is expressed?

How is Phenylalanine hydroxylase deficiency inherited?

What are the possible consequences of not treating PAH in a newborn?

The phenotype of your patient with homocystinuria is similar to what other disorder that you have studied?

In homocystinuria what two amino acids are elevated in the blood?

What causes the hepatomegaly in Von Gierke Disease?

Why do children with Von Gierke become hypoglycemic?

What amino acid builds up in excess in PKU?

What molecule is significantly increased in OTCD?

If a patient with OTC deficiency has an ammonium level over 800 uM/L, what is the MOST appropriate intervention?

What initial diagnostic test should be ordered for Prader-Willi Syndrome?

Which lysosomal enzyme is deficient in Tay-Sachs disease, leading to the accumulation of GM2 gangliosides?

A newborn screening test comes back as 'likely affected' for Glycogen Storage Disease Type 1a, but confirmatory genetic testing reveals no mutation. What is the next step in diagnosis?

A patient with Leigh Syndrome presents with lactic acidosis. What is the MOST appropriate pharmacological intervention in this case?

What is the MOST likely finding on a fundoscopic exam in a patient with Tay-Sachs?

A 5-year-old male is diagnosed with Leigh syndrome. Given the inheritance pattern of mitochondrial DNA, which of the following family members is MOST likely to also have the condition?

Which statement best describes the concept of genomic imprinting?

In Prader-Willi syndrome, which of the mechanisms below can lead to the disease?

If enzyme AB is functioning normally, what is the expected metabolic conversion?

Which of the following inborn errors of metabolism falls into the category of organic acidemias?

Patients which inborn errors of metabolism may experience a worsening of their symptoms due to the consumption of which food additive?

What is the MOST appropriate diagnostic test to CONFIRM Phenylketonuria?

Which sign or symptom differentiates homocystinuria from Marfan Syndrome?

What is the purpose of prescribing betaine anhydrous in the management of homocystinuria?

Which of the following is a potential long-term complication if homocystinuria is poorly managed?

A characteristic physical exam finding in Glycogen Storage Disease Type 1 (Von Gierke) is:

Why is continuous nasogastric (NG) nighttime feeding often required for infants with Glycogen Storage Disease Type 1 (Von Gierke)?

What is The MAIN goal of therapy in Ornithine transcarbamylase deficiency (OTCD)?

Which genetic abnormality results in Leigh syndrome

The severity of Leigh Syndrome symptoms is MOST influenced by:

A deletion of which gene inherited from the father causes Prader-Willi Syndrome?

Which of the following mechanisms can result in Prader-Willi syndrome?

If a gene is maternally imprinted, what does this mean for its expression?

How does genomic imprinting affect inheritance patterns?

What is the MOST likely reason for the elevated lactate levels observed in patients with Leigh syndrome?

Following the nondisjunction of maternal chromosomes, what is the result?

A researcher is studying a novel genetic disorder linked to genomic imprinting. They observe that the disorder only manifests when a specific gene is inherited from the mother, but not from the father. Which epigenetic mechanism is MOST likely responsible for this observation?

A child presents with developmental delay, seizures, ataxia, and elevated lactate levels in both serum and CSF. Further investigation reveals a mutation affecting the assembly of mitochondrial complex I. Assuming the mutation is autosomal recessive, what is the likelihood that the patient's sibling will also be affected, assuming both parents are heterozygous for the mutation?

A 22-year-old woman is pregnant. Her first child has phenylketonuria. She is heterozygous for a PAH mutation. What dietary component should she avoid during this pregnancy to prevent fetal toxicity?

A child with developmental delay, marfanoid habitus, and bilateral downward lens dislocation is found to have elevated homocysteine and methionine. What enzyme is most likely deficient?

A 4-month-old infant presents with hepatomegaly, a round face, thin limbs, and persistent hypoglycemia. Labs show elevated lactate, uric acid, and triglycerides. Which enzyme is deficient?

A 7-month-old Ashkenazi Jewish infant presents with hypotonia, loss of developmental milestones, and a cherry-red macula. What genetic defect is most likely responsible?

A 2-week-old boy presents with lethargy and vomiting. Ammonium levels are elevated and citrulline is low. What is the most likely diagnosis?

A 16-month-old boy has developmental regression, elevated lactate, and hypotonia. MRI shows bilateral basal ganglia lesions. What mitochondrial disorder is most likely?

A teenager with obesity, hypogonadism, small hands and feet, and intellectual disability is found to have a deletion of the paternal 15q11-q13 region. What is the diagnosis?

A child with hand-flapping, speech impairment, and a wide smiling mouth is found to have a maternal deletion of 15q11-q13. What gene is affected?

A child with homocystinuria is started on a methionine-restricted diet. What additional treatments are most appropriate in a pyridoxine-responsive case?

An infant diagnosed with Von Gierke disease is at risk for which emergency complication if prolonged fasting occurs?

A 2-week-old male infant is brought in for vomiting, lethargy, and hypotonia. Labs reveal elevated ammonia and respiratory alkalosis. Citrulline and arginine levels are low. Which genetic principle explains the increased risk in male infants?

A child with a diagnosis of Leigh syndrome has a mutation in mitochondrial DNA. Which inheritance pattern most accurately explains this?

A 7-month-old child of Ashkenazi Jewish ancestry presents with hypotonia, regression, and a cherry-red macula. Genetic testing confirms HEXA mutations. What accumulates in the neurons of this patient?

A pregnant woman with classic PKU has difficulty adhering to a low-phenylalanine diet. Which of the following is the most concerning risk to the fetus?

A 16-year-old boy presents with obesity, small testes, intellectual delay, and hyperphagia. DNA methylation testing confirms loss of SNRPN gene expression. Which chromosomal region is affected?

A child with seizures, severe speech impairment, and a happy demeanor is found to have a deletion of UBE3A. What is the mechanism of this disorder?

A child with homocystinuria is started on pyridoxine, folate, and B12 but continues to have elevated homocysteine. What additional agent is used to promote remethylation to methionine?

A child with GSD1 is being evaluated for a hypoglycemic crisis. Which emergency treatment is contraindicated?

A child with developmental delay and seizures has elevated CSF lactate and alanine. Muscle biopsy confirms a mitochondrial disorder. What metabolic consequence explains the elevated anion gap?

Which of the following would not be expected in a patient with urea cycle disorder presenting with encephalopathy?

A neonate with suspected urea cycle disorder is found to have plasma citrulline levels below normal and high ammonia. Genetic analysis confirms an OTC mutation. What medication is most appropriate to lower ammonia levels?

A child is diagnosed with Leigh syndrome based on elevated serum lactate, developmental regression, and MRI showing basal ganglia lesions. Which additional test would most directly confirm a mitochondrial etiology?

A 16-year-old male with delayed puberty, obesity, short stature, and small hands is found to have maternal uniparental disomy of chromosome 15. What gene is unexpressed in this case?

A newborn presents with hypotonia and feeding difficulties. A cherry-red macula is noted. Enzyme testing shows reduced activity of hexosaminidase A. Which of the following is the most specific consequence of this enzyme deficiency?

A 5-year-old with classic PKU and good dietary control is switched to sapropterin. What biochemical cofactor is being supplemented?

A 4-month-old infant with hepatomegaly and hypoglycemia has elevated triglycerides, uric acid, and lactate. Which metabolic pathway is most directly impaired in this disorder?

A child with speech delay, inappropriate laughter, and ataxia is found to have loss of maternal expression of UBE3A. Which of the following most likely explains this finding?

A neonate with urea cycle disorder has an ammonium level of 900 µmol/L and worsening encephalopathy. What is the most urgent next step?

A child is found to have elevated homocysteine, arachnodactyly, and downward lens dislocation. He is treated with methionine-restricted diet and pyridoxine. Which lab value would indicate successful therapy?

A patient with Tay-Sachs disease is being evaluated for recurrence risk. Which statement is most accurate regarding inheritance?