Objective To
report a
pedigree with
tyrosinemia type Ⅱ,and to analyze its causative
mutations.
Methods Clinical data were obtained from a 10-year-old
male proband with
tyrosinemia type Ⅱ,and analyzed retrospectively.
Blood and
urine samples were collected from 19
persons in 3
generations of the
pedigree,and the
amino acid level was detected in these samples.Genomic
DNA was extracted from all of the 19
family members,and
mutations in the
tyrosine aminotransferase (TAT)
gene were detected.Results The
patient developed
photophobia at 2 months after
birth,and the symptom was gradually aggravated after that.At the age of 6 years,ocular
pain and
photophobia occurred.At the age of 8 years,linear keratotic plaques occurred on his fingertips and soles of both
feet,with obvious tenderness.Ophthalmic examination showed no obvious
abnormalities in corneal
staining or
ocular fundus.
Skin examination showed multiple linear keratotic plaques on the
fingers and soles of both
feet.The
serum tyrosine level was 825.64 μmol/L,and the level of p-hydroxyphenyllactic
acid in
urine was 161.4 μmol/L.
Genetic testing showed 2 novel
mutations,including c.236G > A at position 236 in
exon 2 of the
TAT gene causing the substitution of
glycine by
glutamic acid (p.Gly79Glu),and c.1141G > T at position 1141 in
exon 10 of the
TAT gene leading to the formation of a
premature termination codon instead of
glutamic acid (p.Glu381*).The proband was the only
patient in the
family.Some members in the patrilineal
family carried the
mutation c.1141G > T (p.Glu381*),and some in the maternal
family carried the
mutation c.236G > A (p.Gly79Glu).Conclusion This is the first case of
tyrosinemia type Ⅱ reported in the domestic
population,and 2 novel heterozygous
mutations were identified in the
TAT gene,which may
lead to the occurrence of
tyrosinemia type Ⅱ in the
patient.