PEDBASE.org - The Pediatric Database - Detailed information of HAWKINSINURIA

HAWKINSINURIA

DEFINITION:

A disorder of tyrosine metabolism characterized by the build-up of an eposide metabolite (Hawkinsin) resulting in growth failure and metabolic acidosis.

EPIDEMIOLOGY:

incidence: less than 1/100,000
age of onset:
- newborn
risk factors:
- familial - autosomal dominant
  - chrom.#: ?
  - gene: ?
- M = F

PATHOGENESIS:

1. Background

this condition is thought to be due to a deficiency of one of the components of the 4-OH-phenylpyruvic acid oxidase enzyme complex
this results in the accumulation of an epoxide intermediate which is subsequently metabolized:
- reduced to 4-OH-cyclohexylacetic acid
- reacts with glutathione to form the organic acid Hawkinsin
the degree of symptoms appears to be dependent upon the quantity of protein ingested during infancy; the greater the protein in-take, the greater the clinical symptoms, i.e., metabolic acidosis - the accumulation of Hawkinsin may be toxic and interferes with normal cellular growth and adds anions to the plasma resulting in a metabolic acidosis

CLINICAL FEATURES:

patients usually asymptomatic
if symptomatic, includes:
- failure to thrive
- "swimming pool" odour
- mild hepatomegaly
- normal intelligence -> mental retardation

INVESTIGATIONS:

1. Serum

Hawkinsinemia
severe anion gap metabolic acidosis
ketosis

2. Urine

organic acids:
- Hawkinsinuria
- 4-OH-phenylpyruvic acid, 4-OH-phenylacetic acid, and 4-HCAA
- ketonuria

MANAGEMENT:

1. Diet

low protein diet (breast milk)
low phenylalanine and tyrosine diet
- corrects the metabolic and clinical problems

2. Medical

large doses of Vit C
- up to 1000 mg/day

3. Prognosis

no therapy is needed after 1 year of age
long-term prognosis is excellent

Pediatric Database - HAWKINSINURIA

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