Aminoacidopathies

Question 1

What is maple syrup urine disease?

Answer 1

Autosomal recessive disorder affecting brached chain amino acid complexes.

Deficiency of branched chain alpha ketoacid dehydrogenase complex leading to build up of branched chain complexes (leucine, isoleucine, valine) and ketoacids in blood+urine.

The odour is caused by sotolon

More common in Jews because of founder effect.

Presents with ketoacidosis in neonatal period - vomiting, diarrhoea, hypotonia, seizures, hypoglycemia, pancreatitis, opisthotonus, coma and neurological decline. Smell of maple syrup in urine.

Several types - usually classical (severe). Milder forms and thiamine responsive forms.

Dx: Prenatal diagnosis (culture amniotic cells), increase serum and urine AAs, positive ferric chloride test.

Rx: Dialysis. Low branch-chain diet (life long)

Question 2

What is Type 1 tyrosinemia?

Answer 2

Cannot break down tyrosine -> tyrosinemia

Present with:
Acute/chronic liver failure -> HCC
Renal fanconi's
Rickets (from phosphaturia)
FTT
(cardiomyopathy, dermatological)
Raised phenylalanine

Treatment: Nitisinone (NTBC), then liver transplant if fails.

Question 3

How does Type 2 tyrosinemia present?

Answer 3

Photophobia, excessive tearing
Palmar + plantar hyperkeratosis
Neurological

Question 4

What are some general features of amino acidopathies?

Answer 4

Abnormal transmport + metabolism of AAs
Small molecule - encephalopathy
Metabolic acidosis with raised anion gap (but no lactate) and ketones and raised AA

Question 5

Give 6 examples of amino acidopathies

Answer 5

MSUD
Tyrosinemia
PKU
Cystinuria
Homocystinuria
Hartnup disease

Question 6

What is the genetic inheritance and mutation in PKU?

Answer 6

AR.
Mutation in PAH (phenylalanine hydroxylase) - range from PKU to hyperphenylalanemia
(Chromosome 12)

Question 7

How is screening for PKU done?

Answer 7

1. Guthrie test (bacterial inhibition assay)
2. Immunoassays
3. Amino acid measurement using tandem mass spectometry - look at Phe and Phe/Tyr levels.

Question 8

How does PKU present?

Answer 8

Seizures, metal retardation
Albinism
Microcephaly
Musty smelling urine

Question 9

What is the treatment for PKU?

Answer 9

Diet for life - Avoid phenylalanine in diet - i.e. chicken, meat, egg, cheese.
Avoid too much starchy food
Biopterin supplement
Tyrosine supplement
?Gene therapy

Question 10

What is recommended to mothers with PKU?

Answer 10

Need to make sure phenyalanine level as low as possible. Strict low Phe diet pre-conception and throughout pregnancy.