Patient 2 |
Female |
8 y |
Consanguineous parents |
Learning difficulties |
Psychomotor retardation, ADHD |
Not described/performed |
1769 µmol/L |
Homozygous for A33T mutation in the HPD gene |
Low-Phe/Tyr diet |
Mild intellectual impairment (15 y) |
1- Endo et al.1616. Endo F, Kitano A, Uehara I, Nagata N, Matsuda I, Shinka T, et al. Four-Hydroxyphenylpyruvic acid oxidase de¢ciency with normal fumarylacetoacetase: a new variant of hereditary hypertyrosinaemia. Pediatr Res. 1983:17:92-6. https://doi.org/10.1203/00006450-198302000-00002 https://doi.org/https://doi.org/10.1203/...
|
Male |
Infancy |
Parents were siblings mother had hypertyrosinemia |
Seizures and pneumonia at day 21 of life |
Seizures, encephalopathy |
Mild cerebral atrophy |
640 µmol/L |
Not described/performed |
Low-Phe/Tyr diet |
Died due to accidental asphyxiation (day 105) |
2- Giardini et al.1717. Giardini O, Cantani A, Kennaway NG, D’Eufemia P. Chronic tyrosinemia associated with 4-hydroxyphenylpyruvate dioxygenase deficiency with acute intermittent ataxia and without visceral and bone involvement. Pediatr Res. 1983;17:25-9. https://doi.org/10.1203/00006450-198301000-00005 https://doi.org/https://doi.org/10.1203/...
and D’Eufemia et al.1818. D’Eufemia P, Giardini O, Cantani A, Martino F, Finocchiaro R. Autoimmune thyroiditis in a case of tyrosinemia III. J Inherit Metab Dis. 1992;15:861-2. https://doi.org/10.1007/bf01800222 https://doi.org/https://doi.org/10.1007/...
,1919. D’Eufemia P, Finocchiaro R, Celli M, Viozzi L, Giardini O. Immunological abnormalities in a patient with tyrosinemia type III. J Inherit Metab Dis. 1995;18:355-6. https://doi.org/10.1007/bf00710429 https://doi.org/https://doi.org/10.1007/...
|
Female |
17 mo |
Not relevant |
Acute ataxia, confusion, motor incoordination, hypotonia, absent tendon reflexes |
Recovered from all symptoms |
Not described/performed |
624 µmol/L |
Not described/performed |
Low-protein diet until 3 y |
Autoimmune thyroiditis (9 y) Normal development (17 y) |
3- Cerrone et al.33. Cerone R, Holme E, Schiaffino MC, Caruso U, Maritano L, Romano C. Tyrosinemia type III: diagnosis and ten-year follow-up. Acta Paediatr. 1997;86:1013-5. https://doi.org/10.1111/j.1651-2227.1997.tb15192.x https://doi.org/https://doi.org/10.1111/...
and Rüetschi et al.1414. Rüetschi U, Cerone R, Pérez-Cerda C, Schiaffino MC, Standing S, Ugarte M, et al. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. Hum Genet. 2000;106:654-62. https://doi.org/10.1007/s004390000307 https://doi.org/https://doi.org/10.1007/...
|
Male |
3.5 y |
Not relevant |
Developmental delay from 8 mo |
Psychomotor retardation, hyperactivity, self-injurious behavior, severe speech delay |
Normal |
532 µmol/L |
Heterozygous for Y200X and I335M mutations in the HPD gene |
Low-Phe/Tyr diet until 12 y |
Severe intellectual impairment (14 y) |
4- Tomoeda et al.2020. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, et al. Mutations in the 4-Hydroxyphenylpyruvic acid dehydrogenase gene are responsible for tyrosinemia type III and hawkinisinuria. Mol Genet Metab. 2000;71:506-10. https://doi.org/10.1006/mgme.2000.3085 https://doi.org/https://doi.org/10.1006/...
|
Male |
7 weeks |
Not relevant |
Neonatal restlessness, reduced head control |
Microcephaly |
Not described/performed |
594 µmol/L during treatment |
Homozygous for A268V mutation in the HPD gene |
Low Phe/Tyr diet until 17 y, then low-protein diet |
Moderate intellectual impairment (19 y) |
5- Rüetschi et al.1414. Rüetschi U, Cerone R, Pérez-Cerda C, Schiaffino MC, Standing S, Ugarte M, et al. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. Hum Genet. 2000;106:654-62. https://doi.org/10.1007/s004390000307 https://doi.org/https://doi.org/10.1007/...
|
Male |
7.5 y |
Brother of patient 4 (Table 2) Consanguineous parents |
Urolithiasis |
Essential tremor |
Not described/performed |
830 µmol/L |
Homozygous for Y160C mutation in the HPD gene |
Normal diet |
Mild intellectual impairment (7.5 y) Lost to follow-up |
6- Rüetschi et al.1414. Rüetschi U, Cerone R, Pérez-Cerda C, Schiaffino MC, Standing S, Ugarte M, et al. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. Hum Genet. 2000;106:654-62. https://doi.org/10.1007/s004390000307 https://doi.org/https://doi.org/10.1007/...
|
Male |
18 y |
Brother of patient 5 (Table 2) Consanguineous parents |
Psychomotor retardation |
Essential tremor |
Not described/performed |
262 µmol/L |
Homozygous for Y160C mutation in the HPD gene |
Normal diet |
Lost to follow-up |
7- Ellaway et al.1515. Ellaway CJ, Holme E, Standing S, Preece MA, Green A, Ploechl E, et al. Outcome of tyrosinemia type III. J Inherit Metab Dis. 2001;24:824-32. https://doi.org/10.1023/A:1013936107064 https://doi.org/https://doi.org/10.1023/...
|
Male |
14 y |
Consanguineous parents |
Mild psychomotor retardation, generalized seizures |
Suspected seizures since 2 y |
Not described/performed |
913 µmol/L |
Not described/performed |
Low-protein diet initially, then ceased |
Intellectual impairment (18 y) |
8- Ellaway et al.1515. Ellaway CJ, Holme E, Standing S, Preece MA, Green A, Ploechl E, et al. Outcome of tyrosinemia type III. J Inherit Metab Dis. 2001;24:824-32. https://doi.org/10.1023/A:1013936107064 https://doi.org/https://doi.org/10.1023/...
|
Not described |
18 mo |
Not relevant |
Developmental delay |
None |
Not described/performed |
1305 µmol/L |
Not described/performed |
Low-Phe/Tyr diet |
Mild global developmental delay (6 y) |
9- Tahiroglu et al.2121. Tahiroğlu AY, Mungan NÖ, Firat S, Avci A. Autism symptoms related to tyrosinemia type III: A case report. Turk J Endocrinol Metab. 2008;12:55-6. |
Male |
2 y |
Not described |
Developmental delay from 15 mo |
Psychomotor retardation, hyperactivity, autistic symptoms |
Not described/performed |
“Elevated levels” |
Not described/performed |
Low-Tyr diet |
Severe intellectual impairment (9 y) Persistence of hyperactivity |
10- Szymanska et al.44. Szymanska E, Sredzinska M, Ciara E, Piekutowska-Abramczuk D, Ploski R, Rokicki D, et al. Tyrosinemia type III in an asymptomatic girl. Mol Genet Metab Rep. 2015;5:48-50. https://doi.org/10.1016/j.ymgmr.2015.10.004 https://doi.org/https://doi.org/10.1016/...
|
Female |
11 y |
Not described |
Recurrent proteinuria since 7 y |
None |
Not described/performed |
439 µmol/L |
Homozygous for T160C mutation in the HPD gene |
Normal diet |
Normal development (11 y) |