Inborn Errors: Amino Acidopathies Flashcards
What are the signs and symptoms of phenylketonuria?
Hyperphenylalaninemia
Severe classical PKU: Plasma Phe >1200 µM
Moderate PKU: 600-1200 µM
Mild/benign hyperphe:
What are the approaches for treating a patient with PKU?
Dietary Restrictions:
Restrict Dietary Protein
Supplement with Phe-free medical beverage
Long term maintenance:
Restrict Phe, but do not eliminate it (after childhood)
Provide adequate calories/nutrition: protein, vitamins, minerals
Maintain normal growth
New approaches/therapies for PKU
Biopterin (Sapropterin) Large neutral amino acid supplement Phenylalanine ammonia lyase Macroglyoprotein Liver cell transplant??
What is maternal PKU syndrome?
Maternal PKU syndrome results when an adult woman with PKU does not adhere to a Phe-free diet during pregnancy.
This is linked to microcephaly, intellectual disability, growth retardation, congenital heart defects in the child.
What is the original rationale for newborn screening?
Early identification facilitates timely interventions that result in significant decreases in morbidity, mortality, and disability. PKU can be successfully treated if detected early, before symptoms develop.
What are the amino acids involved in Maple Syrup Urine Disease?
Leucine, Valine, Isoleucine
All of the Branched Chain amino acids.
What are the changes that occur in biochemical intermediates in homocystenuria?
Homocystenuria results from Cystathione synthase deficiency. CS usually converts homocysteine to cystathione, thus increased homocysteine levels result. Homocysteine is also a precursor for methionine, so increased levels of methionine may also result. B12 is a cofactor in its conversion to methionine, so is a treatment option. Cysteine levels will be decreased, so supplemental cysteine is also a treatment.
What are the signs and symptoms of homocystenuria?
Often missed on Newborn Screenings
Marfanoid habitus (tall, thin, very long arms)
Osteoporosis
Scoliosis
Thromboemboli are common in the B6 unresponsive forms
Atherosclerotic disease
Eye abnormalities (Ectopic lens, myopia)
Developmental disability/Neuropsychiatric symptoms
What is the treatment for homocystenuria?
Initial treatment is pyridoxine (via B6) challenge:
750mg Vit B6 for 1 week
Monitor total homocysteine levels and plasma methionine
Hyperhomocystenemia will normalize in pyridoxine responsive forms
If unresponsive: Restrict dietary protein Supplement with methionine free foods Oral Betaine Consider supplementation with B12, folate, and or cysteine
What are the clinical symptoms of Tyrosinemia Type 1?
Liver failure in 1-6 months of brith: Hyperbilirubinemia, prolonged PTT, Elevated transaminases, Hepatomegally, edema
Porphyria-like syndrome: at any age, abdominal pain crisis, peripheral neuropathy
Rickets due to renal tubulopathy (later infancy)
Lab values:
Plasma Tyrosine = 10x normal
Plasma Methionine = 10x normal
Urine: excess succinylacetone and d-ALA
What is the cause of Tyrosinemia Type 1?
Fumarylacetoacetate hydrolase deficiency. FAH degrades Tyrosine into Fumarate and Acetoacetate. Loss of this enzyme causes an increase in Tyrosine. Increased succinylacetone inhibits d-aminolevulinic acid, creating porphyria-like syndrome with abdominal pain.
Treatment is NTBC which increases Tyrosine but prevents creation of fumarylacetoacetate and succinylacetate, preventing many complications of the disease.
Hypertyrosinemia causes keratitis or palmoplantarkeratosis, so Tyrosine and Phenylalanine-free diet is needed.
