Transcript Phenylketonuria case

Clinical Case Presentation
#5
Building Blocks of Life
Phenylketonuria
There will be a test at the end of this
presentation!
24 year old female
Weighs 55 kg
• Chief Complaint (CC)
• Here for a check-up. Has some cold
sensitivity on lower left molar
• History of Chief Complaint (HCC)
• Noticed cold sensitivity over past couple of
months
• Social History (SH)
• No history of smoking/illicit drug use.
Drinks vodka and grapefruit juice 5 x/wk
•Nutritional History (NH)
• Eats a very strict diet which is low in
protein and high in carbohydrates. She
eats/drinks frequently (approx 6 times/day),
and takes phenylalanine free amino acid
supplement drinks 4 times a day (directly
from the bottle).
•Family History (FH)
• Mother is homozygous for PKU gene
mutation
• Dental History (DH)
• Last check-up 5 years ago. Had a number of
amalgam fillings 7 years ago. Brushes twice a
day, doesn’t floss.
• Medical History (MH)
• Phenylketonuria. Monthly blood testing
(Guthrie test) reveals phenylalanine levels
within normal limits over last 5 years.
• Medications
• None
• Review of Systems (RS)
• Fair skin, blonde hair, dry skin, eczema, below
average IQ.
Teeth
Examination Findings
• Extra-oral exam WNL
• Generalized enamel erosion of all tooth
surfaces.
• Lower left first molar sensitive to ice
applied to the occlusal aspect.
• Low plaque index
Diagnosis and Risk Assessment
Are any of the conditions in the history connected
to the enamel erosion ?
1. Phenylketonuria ?
2. Vodka and grapefruit juice?
3. Low protein diet ?
4. High carbohydrate diet ?
5. Frequent eating/drinking ?
6. Long-time between dental check-ups ?
7. Doesn’t floss ?
8. Below average IQ ?
Differential Diagnosis
• Bulemia nervosa: gastric acid
regurgitation
• Erosion due to chronic
consumption of low pH drinks
• Saliva with poor buffering capacity
• Poor oral hygiene
Diagnosis
• Salivary pH at rest is 6.5, stimulated is 7.0
• Patient drinks daily: 4 servings of
lemonade (pH3.1), and 4 servings of
supplement drink (pH 4.1). She never uses
a straw.
• No history of vomiting or gastric reflux.
Phenylketonuria (PKU)
• PKU is an inborn error of metabolism from deficiency of the
enzyme, phenylalanine hydroxylase (found in the liver), or
more rarely, of its tetrahydrobiopterin cofactor .
• The incidence of PKU is approximately 1 in 14,000 in only
the white population of the United States (Celtic origin).
• The hydroxylation of PHE is a required step in both the
normal degradation of the carbon skeleton of this amino
acid and the synthesis of tyrosine.
• The normal blood level of PHE is 30-120 μM (0.5 to 2.0
mg/dL), but it is >1200 μM (20 mg/dL) in phenylketonurics.
• Leads to excessive urinary excretion of phenylpyruvate and
phenyllactate, and, if untreated leads to severe mental
retardation.
• Newborn screening for PKU is mandatory in the United
States. Prenatal diagnosis is now possible using DNA probes
Clinical manifestations
• Decreased pigmentation: PHE is a competitive
inhibitor of tyrosinase in melanocytes.
• Neurological defects: attributed to toxic effects of
phenylalanine, possibly because of reduced
transport and metabolism of other aromatic amino
acids in the brain due to competition from the high
phenylalanine concentration. Patients may have
low IQ, spasticity and a history of seizures.
Pathogenesis of PKU
PKU can be caused by an intron mutation that leads to aberrant
splicing. (A) Normal primary transcript and mRNA. (B)
Mutation of G to A in intron 12 results in the skipping of exon
12. Most mutations causing PKU occur in coding regions.
Treatment & Prognosis
• Phenylketonuria is treatable by a low phenylalanine
diet continued indefinitely. Patients with PKU should
avoid artificial sweeteners (Aspartame). If the Phe
levels are kept normal, prognosis is excellent.
•Gene therapy is in development.
•The plant enzyme phenylalanine ammonia lyase
(PAL) will survive in the gut long enough to deplete
the phenylalanine derived from food protein and so
reduce the rise in blood phenylalanine that otherwise
occurs after a protein meal. Studies are in progress.
Answer the following
•What are this patient’s risk factors for
enamel erosion ?
•What is the pathogenesis of PKU ?
•As a dentist, what recommendations
would you make to patients &/or
parents of patients with PKU ?
Thank You