E.

Smith-Magenis syndrome

26. A 16-year-old adolescent boy has a long face, large cupped ears, high arched
palate, a prominent square jaw, hyperextensible finger joints, flat feet, and
large testes. He also complains from recurrent otitis media, infrequent seizures,
and mild intellectual disability.
Of the following, the MOST likely diagnosis is
A. Jacobsen syndrome
B. Fragile X syndrome
C. Noonan syndrome
D. Trisomy X syndrome
E. Pallister-Killian syndrome

27. A preschool child has prominent full cheeks, abnormal ear lobes, sparse hair
in the temporal regions, pigmentary skin anomalies, supernumerary nipples,
infrequent seizures, and profound intellectual disability. He also had undergone
surgery for diaphragmatic hernia in neonatal period.
Of the following, the MOST likely diagnosis is
A. Jacobsen syndrome
B. Fragile X syndrome
C. Pallister-Killian syndrome
D. Kallmann syndrome
E. Smith-Magenis syndrome

28. A 1-year-old infant presents with hypochromic microcytic anemia, after full
investigations found to have β thalassemia major, Hb electrophoresis were
done for parents showing normal father and mother with β thalassemia minor.
What is the type of inheritance in this case?
A. Chromosome breakage syndrome
B. Uniparental disomy
C. Autosomal dominant inheritance
D. Autosomal recessive inheritance
E. Multifactorial inheritance

29. Which of the following is a classic example of imprinting disorder?

A. Prader-Willi syndrome
B. Cartilage hair hypoplasia
C. Bloom syndrome
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 D. Kallmann syndrome
E. Smith-Magenis syndrome

30. Which of the following is a minor diagnostic criterion for Prader-Willi

syndrome?
A. Feeding problems and failure to thrive as an infant
B. Sleep apnea
C. Weight gain at 1-6 yr
D. Characteristic dysmorphic facial features
E. Small genitalia

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Chapter 9
Human Genetics
Answers
ZUHAIR ALMUSAWI
1.(B) Indications for genetic counseling
Advanced parental age
• Maternal age ≥35 yr
• Paternal age ≥40 yr
2.(A) Genetic counseling has a major role in risk assessment for cancer,
especially breast, ovarian, or colon cancer, for which well-defined risk models
and genetic tests are available to assess risk to an individual.
3.(C) Enzyme replacement therapies are available for Gaucher disease and Fabry
disease, some mucopolysaccharidoses (MPS I, II, IVA, VI), acid lipase deficiency,
and Pompe disease, and are being tested for MPS IIIA, MPS VII, metachromatic
leukodystrophy, α-mannosidosis, Niemann-Pick disease type B, and neuronal
ceroid lipofuscinosis, late infantile (CLN2).
4.(C) Fluorescent in situ hybridization (FISH) can provide information about the
copy number and location of a specific genomic region. Array-based copy
number detection assays can be used to screen for chromosomal deletions
(large and small) and duplications across the genome, but do not provide
information about the orientation or location of genomic regions.
A chromosome analysis (karyotype ) can detect relatively large chromosomal
deletions and duplications and can also be useful in identifying inversions and
chromosomal rearrangements even when they are copy number neutral
changes that do not result in a deletion or duplication of genomic material.
5.(C)
6.(D) Autosomal recessive disorders are characterized by horizontal
transmission , the observation of multiple affected members of a kindred in the
same generation, but no affected family members in other generations.
7.(C) An individual's mitochondrial genome is entirely derived from the mother
because sperm contain relatively few mitochondria, and these are degradated
after fertilization. It follows that mitochondrial inheritance is essentially
maternal inheritance.

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8.(A) Two common errors of cell division may occur during meiosis or mitosis,
and either can result in an abnormal number of chromosomes. The 1st error is
nondisjunction, in which 2 chromosomes fail to separate during meiosis and
thus migrate together into one of the new cells, producing 1 cell with 2 copies
of the chromosome and another with no copy. The 2nd error is anaphase lag, in
which a chromatid or chromosome is lost during mitosis because it fails to move
quickly enough during anaphase to become incorporated into 1 of the new
daughter cells.
9.(B) Mosaicism is an abnormality defined as the presence of 2 or more cell lines
in a single individual. Polyploidy is a common abnormality seen in 1st-trimester
pregnancy losses. Triploid cells are those with 3 haploid sets of chromosomes
(3n) and are only viable in a mosaic form. Triploid infants can be live born but
do not survive long. Triploidy is often the result of fertilization of an egg by 2
sperm (dispermy). Failure of 1 of the meiotic divisions, resulting in a diploid egg
or sperm, can also result in triploidy.
10.(E) Abnormal cells that do not contain a multiple of haploid number of
chromosomes are termed aneuploid cells.
11.(C) Most males with Down syndrome are sterile, but some females have
been able to reproduce, with a 50% chance of having trisomy 21 pregnancies.
12.(A) Hall's criteria to aid in diagnosis of Down syndrome include
 Hypotonia
 Poor Moro reflex
 Flat face
 Upward slanted palpebral fissures
 Small dysplastic ears
 Joint hyperflexibility
 Short neck, redundant skin
 Short 5th digit with clinodactyly
 Single transverse palmar creases
 Pelvic dysplasia
13. (A)
14. (C)
Milestone CHILDREN WITH DOWN SYNDROME UNAFFECTED CHILDREN
Average (mo) Range (mo) Average (mo) Range (mo)
Smiling 2 1.5-3 1 1.5-3
Rolling over 6 2-12 5 2-10
Sitting 9 6-18 7 5-9
Crawling 11 7-21 8 6-11
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Creeping 13 8-25 10 7-13
Standing 10 10-32 11 8-16
Walking 20 12-45 13 8-18
Talking, words 14 9-30 10 6-14
Talking, sentences 24 18-46 21 14-32
15.(D)
16.(B) Detection of cell-free fetal DNA in maternal plasma is also diagnostic and
replacing conventional 1st- and 2nd-trimester screens. Next-generation DNA
sequencing has reduced the cost of this procedure, which has a high degree of
accuracy (98% detection rate) and applicability.
17.(D) Congenital and acquired gastrointestinal anomalies (celiac disease) and
hypothyroidism are common. Other abnormalities include megakaryoblastic
leukemia, immune dysfunction, diabetes mellitus, seizures, alopecia, juvenile
idiopathic arthritis, and problems with hearing and vision.
18.(B)
19.(B)
20.(B)
21.(A)
22.(C) Older children and adults with Turner syndrome have short stature and
exhibit variable dysmorphic features. Congenital heart defects (40%) and
structural renal anomalies (60%) are common. The most common heart defects
are bicuspid aortic valves, coarctation of the aorta, aortic stenosis, and mitral
valve prolapse. The gonads are generally streaks of fibrous tissue (gonadal
dysgenesis). There is primary amenorrhea and lack of secondary sex
characteristics. Most patients tend to be of normal intelligence, but intellectual
disability is seen in up to 6% of affected children.
23.(D) In contrast to Turner syndrome, Noonan syndrome affects both sexes
and has a different pattern of congenital heart disease, typically involving right-
sided lesions.
24.(C) Persons with Klinefelter syndrome are phenotypically male; this
syndrome is the most common cause of hypogonadism and infertility in males
and the most common sex chromosome aneuploidy in humans.
25.(B) Clinical Manifestations of Kabuki Syndrome
Facial
 Long palpebral tissues and eversions of lateral third of lower eyelids
 Ptosis
 Broad, arched eyebrows with sparse hair on lateral third
 Long eyelashes
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  Blue sclerae
 Protuberant ears
 Short nasal columella (depressed nasal tip)
Neurodevelopmental
 Hypotonia
 Developmental delay (IQ about 60; >80 in 10%)
 Low birthweight
 Postnatal growth deficiency
 Microcephaly
 Seizures
 Autism
Extremity/Skeletal
 Short, incurved 5th finger
 Brachydactyly
 Kyphosis
 Joint hyperextensibility
 Persistent fetal fingertip pads
 Hypoplastic finger nails
Cardiovascular
 Multiple forms of congenital heart disease
Other
 Nonimmune hydrops
 Hypothyroidism
 Precocious puberty
 Delayed puberty
 Lymphatic malformations
 Feeding difficulties
26.(B) A clinically significant fragile site is on the distal long arm of chromosome
Xq27.3 associated with the fragile X syndrome. Fragile X syndrome accounts for
3% of males with intellectual disability.
27.(C) Pallister-Killian syndrome is caused by mosaicism for an isochromosome
12p. The presence of the isochromosome 12p in cells gives 4 functional copies
for the short arm of chromosome 12 in the affected cells.
28.(B) Uniparental disomy (UPD) occurs when both chromosomes of a pair or
areas from one chromosome in any individual have been inherited from a single
parent. Examples of UPD are spinal muscular atrophy, cystic fibrosis, cartilage
hair hypoplasia, α- and β-thalassemias, and Bloom syndrome.

150
29.(A) A classic example of imprinting disorder is seen in Prader-Willi syndrome
and Angelman syndrome, 2 very different clinical conditions. These syndromes
are usually associated with deletion of the same region in the proximal long arm
of chromosome 15. A deletion on the paternally derived chromosome causes
Prader-Willi syndrome, while a maternal deletion of the same region as in
Prader-Willi syndrome causes Angelman syndrome.
30.(B)
Consensus Diagnostic Criteria for Prader-Willi Syndrome
MAJOR CRITERIA (1 point each) MINOR CRITERIA (1/2 point each)
1 Neonatal/infantile hypotonia Decreased fetal movement and
infantile lethargy
2 Feeding problems and failure to Typical behavior problems
thrive as an infant
3 Weight gain at 1-6 yr; obesity; Sleep apnea
hyperphagia
4 Characteristic dysmorphic facial Short stature for family by 15 yr
features
5 Small genitalia; pubertal delay and Hypopigmentation for the family
insufficiency
6 Developmental delay/intellectual Small hands and feet for height
disability
7 Narrow hands, straight ulnar border
8 Esotropia, myopia
9 Thick, viscous saliva
10 Speech articulation defects
11 Skin picking

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Chapter 10
Metabolic Disorders
Questions
QAHTAN ALOBAIDY
1. Which of the following inborn errors of metabolism is associated with
neonatal apnea?
A. Hyperphenylalaninemia
B. Tyrosinemia type II
C. Urea cycle disorders
D. Hypermethioninemia
E. Citrullinemia type II

2. Which of the following anticonvulsant drugs may cause hyperammonemia?

A. Valproic acid
B. Paraldehyde
C. Phenobarbital
D. Clobazam
E. Topiramate

3. Which of the following glycogen storage diseases (GSD) is associated with

cardiomyopathy?
A. GSD type Ia (glucose-6-phosphatase deficiency)
B. GSD type Ib (impaired glucose-6-phosphate exchanger)
C. GSD type III (glycogen debrancher enzyme deficiency)
D. GSD type VI (liver glycogen phosphorylase deficiency)
E. GSD type IX (phosphorylase kinase deficiencies)

4. Macrocephaly is a pathognomonic clinical finding associated with inborn

errors of metabolism.
Which of the following is associated with macrocephaly?
A. Mucopolysaccharidoses
B. Sphingolipidoses
C. Glutaric Acidemia Type 1
D. Wolman Disease
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 E. Farber Disease

5. A 3-month-old infant presents with macroglossia, hypotonia, increased serum

creatinine kinase , and cardiomyopathy.
Of the following, the MOST likely diagnosis is
A. glycogen storage disease type II
B. mucopolysaccharidoses
C. oligosaccharidoses
D. sphingolipidoses
E. galactosialidosis

6. A 6-old-male infant presents with exaggerated startle response. His

ophthalmological examination revealed macular cherry-red spot.
Of the followings, the MOST likely diagnosis is
A. GM1 gangliosidosis
B. Tay-Sachs disease
C. Farber disease
D. galactosialidosis
E. sialidosis

7. Which of the following in born errors of metabolism is characterized by

alopecia?
A. Multiple carboxylase deficiency
B. Gaucher disease type 2
C. Steroid sulfatase deficiency
D. Refsum disease
E. Serine deficiency disorders

8. Which of the following inborn errors of metabolism is characterized by

sweaty feet urine odor?
A. Maple syrup urine disease
B. Isovaleric academia
C. Phenylketonuria
D. Tyrosinemia type 1
E. Cystinuria

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9. Which of the following characterize urea cycle defects with
hyperammonemia from other types of inborn error of metabolism with
hyperammonemia?
A. Normal serum pH
B. High bicarbonate value
C. Lactic acidosis
D. Ketosis
E. Hypoglycemia

10. A 6-week-old Infant presents with recurrent attacks of hypoglycemia,

hepatomegaly, ascites, and jaundice. Blood ammonia, pH, and bicarbonate
values are normal.
Of the followings, the MOST likely diagnosis is
A. propionic academia
B. classic galactosemia
C. Zellweger spectrum disorders
D. long-chain fatty acid oxidation defects
E. GLUD1 -related hyperinsulinemic hypoglycemia

11. A concerned family had two children with classic phenylketonuria (PKU),
consult you about the main vital organ damaged by this disease.
Of the following, the BEST answer is the
A. brain
B. kidney
C. skin
D. eye
E. lung

12. What is the BEST time to assess phenylketonurea to avoid false negative
results?
A. 1st 24 hr of life
B. 24-48 hr of life
C. 48-72 hr of life
D. 72-96 hr of life
E. 96-120 hr of life

13. What is the safe level of plasma phenylalanine during pregnancy?

A. <2 mg/dL
154
 B. <4 mg/dL
C. <6 mg/dL
D. <8 mg/dL
E. <10 mg/dL

14. An infant already on treatment for phenylketonuria (PKU) shows evidence

of neurological deterioration despite adequate control of plasma
phenylalanine.
Of the following, the MOST likely cause is
A. cofactor BH4 deficiency
B. non PKU hyperphenylalaninemia
C. transient neonatal hyperphenylalaninemia
D. severe phenylalanine hydroxylase deficiency
E. hyperphenylalaninemia secondary to liver disease

15. What is the MOST common renal manifistation of tyrosinemia type I ?

A. Renal cysts
B. Nephronophthiasis
C. Cortical necrosis
D. Fanconi-like syndrome
E. Renal stones

16. Increased level of α- fetoprotein in the cord blood of affected infants with
tyrosinemia indicate
A. liver damage
B. renal damage
C. neural tube defect
D. cardiac defect
E. hydrocephaly

17. Which of the following result in elevated levels of urinary succinylacetone?

A. Galactosemia
B. Hereditary fructose intolerance
C. Neonatal iron storage disease
D. Citrullinemia type II
E. Tyrosinemia type I

155
18. A-7-month-old infant after weaning from breastfeeding and introduction of
a solid feeding including meet and fish; starts to develop severe metabolic
acidosis, ketosis, failure to thrive, anemia, mild hepatomegaly, renal tubular
acidosis, and an unusual odor. Investigations show elevated level of 4-
hydroxyphenylpyruvic acid in their urine.
Of the following, the MOST likely diagnosis is
A. tyrosinemia type I
B. tyrosinemia type II
C. tyrosinemia type III
D. hawkinsinuria
E. alkaptonuria

19. A concerned parents counsel you about their infant, who had a black-
stained diapers, with ochronosis (dark spots on the sclera and ear cartilage).
Of the following, the MOST likely diagnosis is
A. tyrosinemia type I
B. tyrosinemia type II
C. tyrosinemia type III
D. hawkinsinuria
E. alkaptonuria

20.Nitisinone is reasonable drug use as treatment option in

A. alkaptonuria
B. hawkinsinuria
C. propionic acidemia
D. tyrosine hydroxylase deficiency
E. transient tyrosinemia of the newborn

21. A 14-year-old female had generalized albinism; with history of recurrent

epistaxis, postsurgical bleeding, and abundant menses. Her bleeding time is
prolonged and platelet count is normal?
Of the following, the MOST likely diagnosis is
A. Hermansky-Pudlak Syndrome
B. Chédiak-Higashi Syndrome
C. Griscelli syndrome
D. Vici syndrome
E. Waardenburg Syndrome

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22. A 10-year-old boy presented to emergency unit with stroke. On
examination; he was tall with elongated limbs, arachnodactyly, scoliosis, pectus
excavatum, genu valgum, pes cavus, high arched palate, and crowding of the
teeth.
Of the following, the BEST treatment for this condition is high doses of vitamin
A. B1 (thiamine)
B. B2 (riboflavin)
C. B3 (niacin)
D. B5 (pantothenic acid)
E. B6 (pyridoxine)

23. In classic homocystinuria, thromboembolic episodes involving both large

and small vessels, especially those of the brain, are common and may occur at
any age.
Which of the following is recommended for preventing vascular events in
patients unresponsive to vitamin B6 therapy?
A. Folic acid
B. Betaine
C. Vitamin B12
D. Riboflavin
E. Thiamine

24. A 6-week-old boy present with refusal to feed, vomiting, an exaggerated

startle reaction, severe intractable seizures , cortical atrophy with subcortical
multicystic lesions, and severe developmental delay. Opthalmological
examination reveals bilateral dislocation of ocular lenses.
Of the following, the MOST likely diagnosis is
A. sulfite oxidase deficiency
B. Hartnup disorder
C. maple syrup urine disease
D. isovaleric academia
E. biotinidase deficiency

25. Which of the following inborn errors of metabolism, a high protein diet
results in a favorable response?
A. Sulfite Oxidase Deficiency
B. Hartnup Disorder
C. Maple Syrup Urine Disease
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 D. Isovaleric Academia
E. Biotinidase deficiency

26. Which of the following vitamins in high doses have dramatic clinical and
biochemical improvement in maple syrup urine disease?
A. B1 (thiamine)
B. B2 (riboflavin)
C. B3 (niacin)
D. B5 (pantothenic acid)
E. B6 (pyridoxine)

27. A 3-month-old infant presents with severe vomiting suggesting pyloric

stenosis; but investigations show severe acidosis, hyperammonemia,
hypoglycemia, hypocalcemia, and bone marrow suppression. He had the
characteristic odor of sweaty feet.
Which of the following amino acid defects is blamed in this presentation?
A. Tryptophan
B. Isoleucine
C. Leucine
D. Valine
E. Methionine

28. Which of the following inborn error of metabolism due to amino acidopathy
results in dermatological manifestation in form of pellagra-like rash?
A. Hartnup disorder
B. Biotinidase deficiency
C. Methylglutaconic acidurias
D. Classic maple syrup urine disease
E. Hyperimmunoglobulinemia D syndrome

29. Which of the following inborn error of metabolism due to amino acidopathy
results in dermatological manifestation in form of acrodermatitis
enteropathica?
A. Hartnup disorder
B. Biotinidase deficiency
C. Methylglutaconic acidurias
D. Classic maple syrup urine disease
E. Hyperimmunoglobulinemia D syndrome
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30. Which of the following inborn error of metabolism due to amino acidopathy
results in dermatological manifestation in form of morbilliform rash?
A. Hartnup disorder
B. Biotinidase deficiency
C. Methylglutaconic acidurias
D. Classic maple syrup urine disease
E. Hyperimmunoglobulinemia D syndrome

31. Which of the following inborn errors of metabolism due to amino

acidopathy results in dermatological manifestation in form of intractable
seborrheic dermatitis?
A. Hartnup disorder
B. Biotinidase deficiency
C. Methylglutaconic acidurias
D. Classic maple syrup urine disease
E. Hyperimmunoglobulinemia D syndrome

32. A 10-day-old neonate present as a sepsis-like picture with clinical signs of

severe metabolic acidosis, with a high anion gap. Investigations reveal
ketonuria, hypoglycemia, anemia, neutropenia, and thrombocytopenia. Brain
imaging shows cerebral atrophy, delayed myelination, and abnormalities in the
globus pallidus and other parts of the basal ganglia.
Of the following, the MOST likely diagnosis is
A. Propionic acidemia
B. Isolated homocystinuria
C. Methylmalonic acidemias
D. Combined malonic and methylmalonic aciduria
E. Combined methylmalonic aciduria and homocystinuria

33. A 10- hour- old neonate presents with poor feeding, failure to suck, lethargy,
profound hypotonia, recurrent myoclonic seizures, and hiccups. Blood pH is
normal with negative urine assay for organic acids.
Of the following, the MOST likely diagnosis is
A. sarcosinemia
B. primary trimethylaminuria
C. nonketotic hyperglycinemia
D. primary hyperoxaluria type I
E. creatine deficiency disorder
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34. Which of the following inborn error of metabolism due to amino acidopathy
result in body odor that resembles that of a fish?
A. Sarcosinemia
B. Primary trimethylaminuria
C. Nonketotic hyperglycinemia
D. Primary hyperoxaluria type 1
E. Creatine deficiency disorder

35. To assess the pyridoxine responsiveness in patients with primary

hyperoxaluria type I, the duration of treatment trial should be at least
A. 1 month
B. 2 months
C. 3 months
D. 4 months
E. 5 months

36. A 3-year-old boy suffers from recurrent otitis media, sinusitis, scaly
erythematous maculopapular rash, purpura, and telangiectasia. These skin
lesions proceed to recurrent, severe, and painful skin ulcers on hands and legs.
Investigation reveals a high level of urinary imidodipeptides.
Of the following, the MOST likely diagnosis is
A. prolidase deficiency
B. hyperprolinemia type I
C. hyperprolinemia type II
D. phosphoserine phosphatase
E. phosphoserine aminotransferase deficiency

37. In the 1st few days of life, a full term baby develops a constellation of
metabolic acidosis, jaundice, and mild to moderate hemolytic anemia. Urine
examination shows 5-oxoprolinuria.
Of the following, the MOST likely diagnosis is
A. 5-oxoprolinase deficiency
B. hyperprolinemia type I
C. glutathione synthetase deficiency
D. γ-glutamylcysteine synthetase deficiency
E. γ-glutamyl transpeptidase deficiency

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38. Which of the following drugs in patient with renal failure can cause
hypoglycemia due to substrate limitation?
A. Trimethoprim-sulfamethoxazole
B. Ampicillin
C. Ciprofloxacin
D. Ceftriaxone
E. Vancomycine

39. Which of the following is the MOST common manifestation of hypoglycemia

in the newborn?
A. episodes of cyanosis
B. jitteriness
C. seizures
D. lethargy
E. intermittent apneic spells

40. Catabolism of amino acids results in the production of free ammonia, which
in high concentration is toxic to the CNS.
In healthy term infants, normal levels can reach as high as
A. 50 μmol/L
B. 100 μmol/L
C. 200 μmol/L
D. 300 μmol/L
E. 400 μmol/L

41. Which value of blood glucose concentration a in sick neonate should be

treated vigorously?
A. <25 mg/dL
B. <35 mg/dL
C. <45 mg/dL
D. <55 mg/dL
E. <65 mg/dL

42. Which of the following counter-regulatory hormones act to increase blood

glucose level by mobilizing amino acids from muscle?
A. Glucagon
B. Growth hormone
C. Cortisol
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 D. Epinephrine
E. Thyroxin

43. Which of the following porphyrias causing non-blistering photosensitivity?

A. Congenital erythropoietic porphyria
B. Porphyria cutanea tarda
C. Hereditary coproporphyria
D. Variegate porphyria
E. X-Linked protoporphyria

44. Which of the following anti-epileptic drugs can elevate blood ammonia?
A. Phenobarbital
B. Midazolam
C. Phenytoin
D. Valproic acid
E. Levetiracetam

45. Which of the following is the MOST consistent laboratory finding in

Hutchinson-Gilford progeria syndrome?
A. Low platelet count
B. High c-reactive protein titer
C. Low serum leptin
D. High liver enzyme
E. High blood urea

46. A 15-month-old boy suffers from progressive spastic diplegia with scissoring
of the lower extremities, choreoathetotic movements, loss of already achieved
developmental milestones, and failure to thrive
Which of the following inborn error of metabolism mimics the above
presentation?
A. Glycine encephalopathy
B. Urea cycle disorders
C. Organic acidemias
D. Fatty acid oxidation defects
E. Mitochondrial respiratory chain defects

162
47. A 7-year-old boy had night blindness, myopia, loss of peripheral vision, and
posterior subcapsular cataract with atrophic lesions in the retina resembling
cerebral gyri.
Which of the following is the MOST likely diagnosis?
A. Classic citrullinemia
B. Tyrosinemia type I
C. Hyperargininemia
D. Argininosuccinic aciduria
E. Hyperornithinemia

48. A 3- day-old baby presented with generalized seizures unresponsive to

conventional anticonvulsant therapies. Mother reports abnormal intrauterine
fluttering movements. Laboratory findings show increased concentrations of α-
aminoadipic semialdehyde and pipecolic acid in the CSF, plasma, and urine.
Which of the following is the BEST line of treatment?
A. Magnesium
B. Vitamin B6
C. Calcium
D. General anesthesia
E. Paraldehyde

49. A 9-month-old boy with macrocephaly and normal developmental

milestones, after a minor Infection he suddenly lost head control followed by
seizures, generalized rigidity, dystonia, and choreoathetosis. Brain imaging
reveals increased extra axial fluid with stretched bridging veins, cortical atrophy,
and fibrosis.
Of the following, the MOST likely diagnosis is
A. glutaric aciduria type 1
B. Canavan disease
C. leukodystrophy
D. hyperprolinemia type II
E. Alexander disease

50. A 8-month-old boy presents with refusal to feed, nausea, vomiting, and
mild diarrhea after ingestion of a high-protein meal. Physical findings reveal
moderate hepatosplenomegaly, thin extremities with moderate centripetal
adiposity, and growth retardation. Laboratory findings show hyperammonemia,

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increased serum ferritin, hypercholesterolemia, and hypertriglyceridemia with
increased urinary levels of lysine, arginine, and ornithine.
Of the following, the MOST likely diagnosis is
A. Alexander disease
B. cystinurea
C. glutaric aciduria
D. familial protein intolerance
E. argininosuccinic aciduria

51. A 6-month-old boy presents with progressive macrocephaly, severe

hypotonia, persistent head lag, and delayed milestones. Head CT scan reveals
diffuse white matter degeneration, primarily in the cerebral hemispheres, with
less involvement of the cerebellum and brainstem.
Of the following, the MOST likely diagnosis is
A. glutaric aciduria type 1
B. Canavan disease
C. leukodystrophy
D. hyperprolinemia type II
E. Alexander disease

52. An adolescent boy after prolonged exercise presented with muscle pain and
dark color urine, his serum levels of creatine kinase was highly elevated with
normal glucose level, muscle biopsy showed increased deposition of neutral fat.
Which of the following is the MOST likely diagnosis?
A. Primary carnitine deficiency
B. Plasma membrane carnitine transport defect
C. Carnitine palmitoyltransferase-II deficiency
D. Carnitine:Acylcarnitine translocase deficiency
A. McArdle disease

53. Which of the following peroxisomal disorders has normal VLCFA levels?
A. Bifunctional enzyme deficiency
B. Zellweger spectrum disorder
C. Acyl-CoA oxidase deficiency
D. Neonatal adrenoleukodystrophy
E. Rhizomelic chondrodysplasia punctate

164
54. A newborn has short proximal upper and lower limbs; examination reveals
cataract with length, weight, and head circumference below 3rd percentile.
Radiologic imaging shows metaphyseal cupping and disturbed ossification with
vertebral bodies coronal cleft.
Which of the following is the MOST likely diagnosis?
A. Achondroplasia
B. Hypochondroplasia
C. Kyphomelic dysplasia
D. Rhizomelic chondrodysplasia punctate
E. Spondylo epiphyseal dysplasia congenital

55. A previously well 7-year-boy presents with hyperactivity, inattention, and

worsening school performance, followed by disturbance of vision, ataxia,
seizures, and strabismus. Within one year he progressed rapidly to increasing
spasticity and paralysis, visual and hearing loss, with loss of ability to speak and
swallow.
Of the following, the MOST likely diagnosis is
A. multiple sclerosis
B. Alexander disease
C. Adrenoleukodystrophy
D. Refsum disease
E. Charcot-Marie-Tooth disease

56. A 10-year-old boy had xanthomas that cause thickening of the Achilles
tendon and extensor tendons of the hands, with cutaneous lesions on the
hands, elbows, knees, and buttocks with positive family history of premature
heart disease in both parents. Investigations show elevated plasma cholesterol
level (800 mg/dL), normal triglyceride level, and slightly decreased HDL level.
Of the following, the MOST likely diagnosis is
A. sitosterolemia
B. familial defective ApoB-100
C. polygenic hypercholesterolemia
D. homozygous familial hypercholesterolemia
E. heterozygous familial hypercholesterolemia

57. A 10-year-old boy presented to emergency room as severe acute abdominal

pain. Examination shows eruptive xanthomas on the arms, knees, and buttocks,

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with hepatosplenomegaly. A milky serum was observed during sample
processing.
Of the following, the MOST likely diagnosis is
A. Tangier disease
B. hepatic lipase deficiency
C. familial chylomicronemia
D. familial hypertriglyceridemia
E. primary hypoalphalipoproteinemia

58. Secondary causes of transient hypertriglyceridemia should be ruled out

before making a diagnosis of familial hypertriglyceridemia.
Which of the following medications is a recognized cause of secondary
hypertriglyceridemia?
A. Progesterone
B. Thiazides
C. Anabolic steroids
D. Carbamazepine
E. Cyclosporine

59. Which of the following conditions may cause reduced high-density

lipoprotein?
A. Sepsis
B. Stress
C. Hepatitis
D. Malnutrition
E. Renal failure

60. Treatment of hypertriglyceridemia in children rarely requires medications.

Dietary restriction of fats, sugars, and carbohydrates, accompanied by increased
physical activity is the main steps of management.
Which of the following levels is an indication for medical treatment despite the
above mentioned measures?
A. >200 mg/dL
B. >400 mg/dL
C. >600 mg/dL
D. >800 mg/dL
E. >1,000 mg/dL

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