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ABP breakdown

Metabolic disorders = 1.5% of the


Genetics = 2.5% of the exam

A family, who is new to the area, brings their 10-month-old son to establish care. Their child has
marked developmental delays, poor growth, and episodic seizures. He was first noticed to have
seizures at 4 months of age, and his development diminished from that point. Of significance is his
sparse short hair that is very lightly colored and easily broken.

Which of the following tests is most likely to be abnormal?

A. Increased urinary dermatan sulfate
B. Elevated urinary metanephrines
C. Decreased serum copper levels
D. Decreased serum zinc levels
E. Elevated serum ceruloplasmin
Menkes disease

• (kinky hair) disease

• X-linked recessive dysfunction of
copper metabolism  impaired
absorption and transport
• Associated with intellectual
disabilities, collagen abnormalities
(skeletal and vascular pathology), and
abnormal hair
• Present early with seizures and
developmental delay
A 6-month-old boy presents for his first evaluation following birth after his mother fled from
his abusive father and entered a shelter. Reportedly, the boy’s father refused to allow his
mother to leave the home even for routine pediatric care. He takes a cow’s milk-based infant
formula and reportedly feeds well. However, his mother reports a history of frequent
vomiting. She also describes two previous episodes consistent with generalized seizure
activity. On examination, his weight is below the 3rd percentile. He is not able to roll over and
has poor head control. His mother also reports that his wet diapers “always smell musty.”

Which of the following findings is most likely to be identified upon further evaluation of this patient?

A. Elevated serum levels of homogentisic acid

B. Hyperammonemia

C. Elevated serum levels of phenylalanine

D. Elevated serum levels of alloisoleucine

E. Hyperuricemia
• Autosomal recessive disorder
• Absence (or near absence) of
phenylalanine hydroxylase
• Phenylalanine accumulates in the serum
and is converted to phenylpyruvate
(musty odor)
• Typical characteristics: blonde hair, blue
eyes, lightly pigmented skin, eczema
• Newborn screening detects high
phenylalanine levels and low tyrosine
Treatment of PKU

Dietary restriction of phenylalanine should begin immediately

Breast milk is relatively low in phenylalanine

Ideally  breastfed and partially supplemented with phenylalanine-free

commercial formula

Dietary restrictions are hard (phenylalanine containing food: meat, chicken, fish,
breads, nuts, cheeses, dietary foods, soft drinks)
A 30-month-old developmentally delayed boy is noted to have recently
experienced further neurologic deterioration in association with the
development of communicating hydrocephalus. He is in the 5th percentile for
height and has coarse facial features, a prominent forehead, and
hypertelorism. Hepatosplenomegaly and generalized joint stiffness are also

Which of the following complications is most likely to occur as this patient grows older?

A. Recurrent pulmonary emboli

B. Recurrent bowel obstruction

C. Myocardial hypertrophy

D. Renal tubular acidosis

E. Pancreatic insufficiency
• X-linked disorder (aka
mucopolysaccharidosis (MPS)
Type 2)  deficiency of
Hunter lysosomal enzymes
Syndrome • Deficiency of iduronate 2-
sulfatase (IDS)
• Low IDS levels lead to increase
in degraded GAGs
(glycosaminoglycans)  causing
thickening in tissue, affecting
brain, bones, heart, lungs, liver,
and spleen.
• Clinical findings: short stature,
multiple skeletal deformities,
joint stiffness, thickened skin,
hypertelorism, and coarse facial
You are asked by a colleague to review the course of a child of Louisiana Cajun descent, who
was apparently normal until 6 months of age. Exam at that time was only remarkable for an
exaggerated startle response. From that date, she started to show lack of normal
development, increasing muscle weakness, and hearing loss. Concerns have recently been
raised about her vision as well.

On examination at the age of 11 months, the child is unable to sit unsupported. Her exam
also shows the development of a cherry red spot on fundoscopic exam.

Which of the following is the most likely diagnosis?

A. Wilson disease
B. Niemann-Pick disease
C. X-linked adrenoleukodystrophy
D. Tay-Sachs disease
E. Gaucher disease
Tay-Sachs disease

Autosomal recessive—Defect in ganglioside metabolism—Accumulation of lipids in neural structures leads

to progressive neurological deterioration  loss of vision, stamina, and muscle tone—An early sign is often
an increased startle response at 3-6 months of age—Cherry red spot on the retina (ganglioside
deposition)—Diagnosis decreased serum levels of hexosaminidase A
A 7-year-old boy with a history of attention-deficit/hyperactivity disorder (ADHD) presents for
evaluation because his parents are concerned that he is “overmedicated.” He has been taking an
extended preparation of methylphenidate (36 mg) for the previous 4 months because of impulsive
behavior, outbursts of aggression, and difficulty staying on task. Over the last week he has, at times,
been “walking like he is drunk” and had difficulty maintaining his balance and climbing stairs. Also, his
parents were recently contacted by his teacher because of “slurred speech and poor handwriting.” On
physical examination, he is visibly upset, refuses to follow simple commands, and is slurring his words.
His gait is ataxic. Additional findings include increased deep tendon reflexes in the lower extremities,
bilateral ankle clonus, and hyperpigmentation in the axilla and over the knees and elbows.

Which of the following tests is most likely to be abnormal upon further evaluation of this patient?

A. Levels of serum ceruloplasmin

B. Levels of serum creatinine kinase, aspartate aminotransferase, and lactate dehydrogenase

C. Levels of serum triglycerides, cholesterol, and phospholipids

D. Levels of glycosaminoglycans in the urine

E. Levels of plasma very long-chain fatty acids

• X-linked recessive

• Disorder of peroxisomal degradation of fatty

acid = accumulation of very long-chain fatty
acids in the central and peripheral nervous
system and adrenal glands

• Usually presents between 5 – 15 years of age

• Due to cortisol deficiency, there is increased

production of ACTH precursor
(proopiomelanocortin {POMC}) = increased
melanin synthesis and hyperpigmentation of
the knees, elbows, palmar creases, axillae,
and gingival borders

• Additional s/s: seizures, impaired auditory

discrimination, and visual disturbances

• CT/MRI: symmetric periventricular white

matter lesions in the posterior parietal and
occipital regions of the CNS
A 3-year-old developmentally delayed and deaf male is referred for
macrocephaly. His head circumference is > 97th percentile. Facial features are
coarse; additional clinical findings include joint stiffness,
hepatosplenomegaly, thickened skin, corneal clouding, and congenital
dermal melanocytosis.

These findings are due to a deficiency in which of the following?

A. Cystathionine β-synthase
B. Biotinidase
C. Pyruvate kinase
D. Lysosomal enzymes
E. Galactokinase
Hurler Syndrome

• Mucopolysaccharidosis type 1
• Autosomal recessive – deficient
activity of lysosomal enzyme α-L-
• Affected infants appear normal at
birth; during the first year of life, they
develop coarse facial features,
flattened midface, skeletal
abnormalities, developmental delay
• Also develop corneal clouding,
deafness, frequent sinus/pulmonary
infections, cardiac abnormalities
• Poor prognosis – average age at
death is 5 years