Amino Acid Disorders Flashcards
Alkaptonuria
Inheritance: Autosomal recessive
Amino acid pathway: Tyrosine breakdown
Deficient enzyme: Homogentisate 1,2-dioxygenase (leads to buildup of homogentisic acid)
Major features:
- Black urine
- Bone/cartilage necrosis
- Height loss secondary to spinal changes
- Aortic/mitral valve calcification
Treatment:
- Dietary Phe and Tyr restriction
- Nitisone can inhibit enzyme responsible for buildup of homogentisic acid
Homocystinuria
Inheritance: Autosomal recessive
Amino acid pathway: Methionine synthesis
Deficient enzyme: Cystathionine Beta-Synthase (Catalyzes the first step in the breakdown of homocysteine into methionine)
Major features:
-Marfanoid habitus/features (including pectus deformities and ectopia lentis)
-Distinguishable from Marfan by:
-Presence of intellectual disability (not seen in Marfan)
-Thromboembolitic events (strokes) (Vessel/aortic
dilation seen in Marfan)
-Joint contractures (Joint laxity seen in Marfan)
-Hypopigmentation
-Seizures
-Risk for MI
-MVP
-Psychiatric problems
Treatment:
- Vitamin B6 (pyridoxine) is effective for 50% of patients
- Protein restricted diet
- Betaine provides alternate pathway for breakdown of homocysteine
- Risk for excess methionine with this treatment
- If residual enzyme activity is present, folate and vitamin B12 can optimize enzyme activity
Maple Syrup Urine Disease (MSUD)
Inheritance: Autosomal recessive
Amino Acid Pathway: Branched-chain amino acids (isoleucine, leucine, valine)(“I Love Vermont’s Maple Syrup”)
Deficient enzyme: Branched-chain alpha-ketoacid dehydrogenase complex
Major features:
- Urine smells like maple syrup
- Developmental delay
- Poor feeding
- Lethargy
- Opisthotonic posturing
- Respiratory failure
- Encephalopathy with illness
Treatment:
- AVOID LEUCINE
- Dietary leucine restriction/high calorie leucine free formulas
Phenylketonuria (PKU) -Inheritance and Enzyme
Inheritance: Autosomal recessive
Amino acid pathway: Phenylalanine Tyrosine
-Tyrosine is involved in pigmentation, inability to convert Phe to Tyr results in the characteristic pale hair/skin of individuals with PKU
Deficient enzyme: Phenylalanine hydroxylase
Phenylketonuria (PKU) - Untreated Symptoms
Major features (untreated):
- Severe intellectual disability
- Microcephaly
- “Musty odor”
- Seizures
- Behavioral problems
- Exaggerated neurologic reflexes
Phenylketonuria (PKU) - Treated Symptoms
Major features (treated):
- Dependent on how well treatment is maintained
- Psychiatric problems
- Learning difficulties/lower IQ
Phenylketonuria (PKU) - Treatment
Treatment:
- Dietary Phe restriction
- Special low Phe foods/formulas
- If an individual has residual enzyme activity, biopterin supplementation may help improve enzyme activity
Maternal PKU
Mother’s with PKU who do not maintain treatment will expose their fetuses to high Phe levels
Fetal features:
- Microcephaly
- IUGR
- Intellectual disability
- Increased risk for CHDs
Tyrosinemia - Inheritance and Enzymes
Inheritance: Autosomal recessive
Amino acid pathway: Tyrosine breakdown
Deficient enzyme: 4-fumarylacteoacetase (Type I), Tyrosine transaminase (Type II), p-Hydroxyphenyl pyruvate dioxygenase (Type III)
PATIENTS SMELL LIKE CABBAGE
Tyrosinemia Type I
Features:
- MOST SEVERE
- HSM
- Acute liver failure/jaundice
- Renal failure
- Rickets – leg bone deformity
- Failure to thrive
- Chronic weakness
Treatment:
-Orfadin – blocks 2nd step in enzyme pathway to prevent buildup of toxic metabolite
Tyrosinemia Type II
Features:
- Keratosis palmoplantaris (hyperkeratosis of hands and feet)
- Intellectual disability (~50%)
- Ocular and cutaneous findings
- Growth retardation
Treatment:
-Dietary restriction of Phe and Tyr
Tyrosinemia Type III
Features:
- Rarest
- Normal liver function
- Mild intellectual disability
- Seizures
Treatment:
-Dietary restriction of Phe, Tyr, and Met
