Alternative titles; symbols
SNOMEDCT: 17820009, 33116002, 72945002; ORPHA: 79155; DO: 0112257;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q22.2 | ?Hydroxykynureninuria | 236800 | Autosomal recessive | 3 | KYNU | 605197 |
A number sign (#) is used with this entry because of evidence that hydroxykynureninuria is caused by homozygous mutation in the KYNU gene (605197), which encodes kynureninase, on chromosome 2q22. One such family has been reported.
Hydroxykynureninuria, also known as xanthurenicaciduria, is an autosomal recessive condition characterized by high urinary excretion of kynurenine (KYN), xanthurenic acid (XA) and 3-hydroxykynurenine (3-OHKYN), with no detectable anthranilic acid (AA) or 3-hydroxyanthranilic acid (3-OHAA) (Christensen et al., 2007).
Komrower et al. (1964) described a female patient, an only child, who excreted large amounts of kynurenine, 3-hydroxykynurenine, and xanthurenic acid in the urine. Absence of kynureninase resulting in a block in the pathway from tryptophan to nicotinic acid, was postulated. Under these circumstances tryptophan is no longer a source of nicotinic acid and deficiency of the vitamin can develop. The mother excreted 3 to 4 times normal amounts of xanthurenic acid. The father's excretion was at the upper limit of normal.
Tada et al. (1967) reported this disorder in a brother and sister with mental retardation. The parents were first cousins. The patients excreted excessive amounts of xanthurenic acid, kynurenic acid, 3-hydroxykynurenine, and kynurenine after tryptophan loading. This disturbance was temporarily corrected by large doses of vitamin B6. The activity of kynureninase in the liver was markedly reduced. The activity was appreciably restored by the addition of pyridoxal phosphate.
In 6 of 9 children born of first-cousin Algerian parents, Cheminal et al. (1996) found muscular hypertonia, psychomotor retardation, stereotyped gestures, congenital deafness, and nonprogressive encephalopathy. Each of the affected children had episodes of sudden worsening of their neurologic status. These episodes occurred spontaneously or during viral illnesses. At the age of 37 months, one female child had an episode of tachycardia, irregular breathing, and arterial hypotension, leading to coma and death. Two children developed renal tubular dysfunction and renal or metabolic acidosis. The only biochemical abnormality noted in these children was a massive hyperkynureninuria, seen only during periods of coma or after intravenous protein loading. Cheminal et al. (1996) suggested that a novel anomaly of tryptophan metabolism occurred in this family because the findings differed from those reported in other families with abnormalities of tryptophan metabolism in which kynureninemia occurred with clinical signs of cerebellar ataxia, developmental retardation, and pellagra (Komrower et al., 1964; Salih et al., 1985). See 260650.
Christensen et al. (2007) reported a patient who presented with jaundice and vomiting at 9 days of age. On routine screening, he was found to have an abnormal metabolite that was eventually identified as xanthurenic acid. The patient recovered, and grew and developed normally, with no issues at follow-up at age 6 years. Christensen et al. (2007) found high excretions of xanthurenic acid, kynurenin, and 3-hydroxykynurenin.
The pattern of transmission of hydroxykynureninuria in the family reported by Christensen et al. (2007) was consistent with autosomal recessive inheritance.
In a boy with massive excretion of xanthurenic acid, 3-hydroxykynurenin, and kynurenine, Christensen et al. (2007) detected homozygosity for a thr198-to-ala (T198A) mutation in the KYNU gene (605197.0001). The homozygous mutation was also present in the boy's brother, who was healthy but had similar excretion of tryptophan metabolites. Both parents and 1 sib were heterozygous for this mutation; 2 remaining sibs did not carry this substitution. The heterozygous sib excreted slightly increased amounts of xanthurenic acid. Urinary excretion and plasma concentrations of tryptophan metabolites were within reference values for other family members.
Cheminal, R., Echenne, B., Bellet, H., Duran, M. Congenital non-progressive encephalopathy and deafness with intermittent episodes of coma and hyperkynureninuria. J. Inherit. Metab. Dis. 19: 25-30, 1996. [PubMed: 8830173] [Full Text: https://doi.org/10.1007/BF01799345]
Christensen, M., Duno, M., Lund, A. M., Skovby, F., Christensen, E. Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase. J. Inherit. Metab. Dis. 30: 248-255, 2007. [PubMed: 17334708] [Full Text: https://doi.org/10.1007/s10545-007-0396-2]
Komrower, G. M., Westall, R. Hydroxykynureninuria. Am. J. Dis. Child. 113: 77-80, 1967. [PubMed: 6015911] [Full Text: https://doi.org/10.1001/archpedi.1967.02090160127016]
Komrower, G. M., Wilson, V., Clamp, J. R., Westall, R. G. Hydroxykynureninuria: a case of abnormal tryptophane metabolism probably due to a deficiency of kynureninase. Arch. Dis. Child. 39: 250-256, 1964. [PubMed: 14169454] [Full Text: https://doi.org/10.1136/adc.39.205.250]
Salih, M. A. M., Bender, D. A., McCreanor, G. M. Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts. Pediatrics 76: 787-793, 1985. [PubMed: 4058988]
Tada, K., Yokoyama, Y., Nakagawa, H., Yoshida, T., Arakawa, T. Vitamin B6 dependent xanthurenic aciduria. Tohoku J. Exp. Med. 93: 115-124, 1967. [PubMed: 5586569] [Full Text: https://doi.org/10.1620/tjem.93.115]