MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: HPD

4-hydroxyphenylpyruvic acid oxidase deficiency
4-hydroxyphenylpyrvate dioxygenase deficiency

Mental retardation
Seizures
Hypotonia
Confusion

Tyrosinemia, Type III

Clinical Characteristics

General description (for patients): 

This condition causes primarily neurological problems with mental impairment being the outstanding sign.  These are usually mild to moderate in severity.  Weakness, unsteadiness, confusion, poor muscle coordination, and mental slowness are the primary signs.  Convulsions may also occur but no liver damage as opposed to other types.  A few patients seem to develop normally.

Medical description:  

This extremely rare disorder remains to be fully defined.  It is known that intellectual and mental impairment is a frequent finding.  Some neonates have had ‘jitteriness’ and restlessness and others are hyperactive.  Ataxia, seizures, confusion, hypotonia, lethargy and purposeless movements have been reported. Skin and hair seem to be normal as are hepatic and renal functions.   A few seem to develop normally.

Genetics:

A mutation in the HPD gene on chromosome 12 (12q24-qter) is responsible for type III tyrosinemia.  The autosomal recessive HPD gene encodes the enzyme 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine.  A novel mutation (85G>A) in this gene has been found in a single Pennsylvania Mennonite patient with an unusual phenotype.

Treatment:

A strict low tyrosine diet has been proposed and would seem to have merit at least in infancy but no data exist to prove this.  Since tyrosine is derived from phenylalanine, restriction of the latter might also be therapeutic.

Prognosis:

Permanent neurological impairment.

Ancillary treatments and support:

Supportive care as appropriate.

Specialists and specialty centers:

Neurologist, Pediatrician.

References:

Puffenberger, E.G.:  Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania.  J. Med. Genet. (Semin. Med. Genet) 121C: 18-31, 2003.  PubMed ID: 12888983

Ellaway, C.J., Holme, E., Standing, S., Preece, M.A., Green, A., Ploechl, E., Ugarte, M., Trefz, F.K., and Leonard, J.V.: Outcome of tyrosinaemia type III.  J. Inherit. Metab. Dis. 24: 824-832, 2001.  PubMed ID: 11916315 

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