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SHORT COMMUNICATION
SUMMARY
Hereditary tyrosinaemia type 1 is a rare but serious metabolic disorder with an autosomal recessive mode of
inheritance. We describe the prenatal diagnosis of an affected fetus performed by DNA-mutation analysis and a
subsequent pregnancy with a healthy child in the same family. ? 1997 by John Wiley & Sons, Ltd.
Prenat. Diagn. 17: 964966, 1997
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INTRODUCTION
Hereditary tyrosinaemia type 1 (MIM 276700)
is an autosomal recessive disorder caused by
the deficiency of fumarylacetoacetase hydrolase
(FAH) (EC 3.7.1.2), the enzyme which takes part
in tyrosine metabolism (Goldsmith and Laberge,
1989). The disease has an acute and a chronic
form, the former presenting with severe hepatic
failure and the latter with tubulopathy, rickets,
and slowly progressive liver cirrhosis with a high
risk of hepatocellular carcinoma. An intermediate
phenotype also occurs as well as pseudodeficiency
*Correspondence to: Aki Mustonen, MD, Department of
Clinical Genetics, Tampere University Hospital, P.O. Box 2000,
SF-33520 Tampere, Finland.
CASE REPORT
The first child (a boy) of a Finnish family was
admitted to hospital at the age of 6 weeks because
of severe hepatic failure. High urinary excretion of
succinylacetone and reduced activity of FAH in
fibroblasts confirmed the diagnosis tyrosinaemia
type 1. A successful liver transplantation was performed at 45 months of age. His parents originate
from the same rural areacounty of Pohjanmaa
where the tyrosinaemia gene is known to exist
enriched. An extensive study of parish records
showed common ancestry of both parents 11
generations earliernot an uncommon finding in
this rural isolate.
After genetic counselling, the family asked for
prenatal examinations in the following pregnancy.
A sample of chorionic villi was taken at 12+4
weeks of pregnancy. It was analysed together with
the DNA specimens of both parents essentially as
described (St-Louis et al., 1994; Ploos van Amstel
et al., 1996).
The parents both showed heterozygosity for the
W262X mutation in exon 9 of the FAH gene. The
fetus was found to be homozygous for the mutation and the parents decided to terminate the
pregnancy. Post-mortem examination of the fetus
did not show structural anomalies. At the time of
termination (at 16+2 weeks) the succinylacetone
concentration in amniotic fluid, as measured
by mass fragmentography, was 063 mg/mmol
creatinine. The concentration of succinylacetone
in normal amniotic fluid samples analysed simultaneously was below the detection limit of the
method. Thus, we estimated that amniotic fluid
succinylacetone was at least 50 times higher than
normal, which confirmed the diagnosis of fetal
tyrosinaemia type 1.
In the next pregnancy, chorionic villus biopsy,
taken at the 13th week, showed the fetus to be
heterozygous for the W262X mutation and subsequently the mother gave birth to a healthy child.
DISCUSSION
Type 1 tyrosinaemia is a rare metabolic autosomal recessive disorder with a variable clinical
picture. The basic defect, deficiency of fumarylacetoacetase (FAH), causes accumulation of the
cytotoxic metabolites maleylacetoacetic acid and
fumarylacetoacetic acid, as well as the pathognomonic metabolite succinylacetone. These
? 1997 by John Wiley & Sons, Ltd.
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