Rett's Syndrome and Ornithine Carbamoyltransferase Deficiency

Thomas, S.; Hjelm, M.; Oberholzer, V. G.; Brett, Elise M.; Wilson, John

doi:10.1016/s0140-6736(87)91219-0

Cited by 15 publications

(6 citation statements)

References 5 publications

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“…In four cases of partial OTC deficiency we found peak orotic acid excretions ranging from 84 to 466 #mol/mmol creatinine. Our results in two of the five RS girls and one of the mothers are consistent with carrier status for OTC, a similar proportion to that found by Thomas et al (1987).…”

Section: Discussionsupporting

confidence: 88%

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Rett's syndrome and ornithine carbamoyltransferase deficiency

Carpenter

Bonham

1990

J of Inher Metab Disea

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Rett's syndrome (RS) is a neurodegenerative disorder which affects 1 in 10000-t5 000 girls. Arrest of development usually occurs at 6-18 months and there is a loss of acquired hand skills and development of stereotypical hand movements. Communication and motor skills are severely impaired (Rett, 1977).Many clues to the possible pathogenesis of the disorder have been described including chromosomal fragile sites at Xp22, abnormal metabolism of biotin and tetrahydrobiopterin, and disturbed X inactivation (Riccardi, 1986). Hyperammonaemia has been described in some cases and the link with the urea cycle enzymes is strengthened by recent reports of increased orotic acid excretion following intravenous alanine loading (Thomas et al, 1987).In this study we describe the results of measurement of plasma ammonia and orotic acid excretion following intravenous alanine loading in five affected girls and their mothers. PATIENTS AND METHODSFive girls from four families and their mothers were given alanine loads according to the method of Kay et al. (1987). L-alanine (0.25 g/kg) in an aqueous solution of 1.12mmol/L was administered over about 10 rain. Plasma samples for ammonia estimation were taken pre-load and at about 10min intervals for 1 h. Basal urines were followed by random specimens collected over a 4-h period post-load. Plasma ammonia was estimated by an enzymatic assay and urinary orotic acid by high performance liquid chromatography.The five girls tested included two sisters, both of whom show many of the characteristic features of RS. The younger girl (case2) is somewhat less severely retarded than her sister but the evidence suggests she does have the same disorder. The three other cases studied all have RS based on the criteria of the Rett Syndrome Diagnostic Work Group (1988). 308

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Section: Discussionsupporting

confidence: 88%

“…Hyperammonaemia has been described in some cases and the link with the urea cycle enzymes is strengthened by recent reports of increased orotic acid excretion following intravenous alanine loading (Thomas et al, 1987).…”

mentioning

confidence: 93%

Rett's syndrome and ornithine carbamoyltransferase deficiency

Carpenter

Bonham

1990

J of Inher Metab Disea

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“…It is of particular interest that the index case, the girl with classical RTS, has a recombination in region Xp21. The data reported by Thomas et al [1987] further supports the possibility that the region around OTC might be of interest. Supporting information is suggested by the comment in Thomas et al [19901 that OTC might be a marker for RTS.…”

Section: Discussionsupporting

confidence: 56%

Segregation analysis of the X‐chromosome in a family with rett syndrome in two generations

Anvret

Wahlström²,

Skogsberg

et al. 1990

Am. J. Med. Genet.

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We report on the first family in which Rett syndrome (RTS) appeared in two consecutive generations. The index case is a 12-year-old girl (classical RTS); her maternal aunt, age 44 years, has mild RTS. Clinically, the family illustrates the wide phenotypic variability between cases, particularly in severity of neurological manifestations. We have analyzed the short arm of the X-chromosome of the family with gene technology. This did not uncover any genetic marker for diagnosis, but it did suggest how the syndrome might have segregated in the family. A cytogenetic analysis gave no information about chromosome abnormalities.

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“…However, band Xp21, which is a late replicating band (very frequently observed after the short rH] dTTP pulse), sometimes appeared much earlier and was observable after Rbanding in a significantly high frequency in the RS patients' cells. This apparent alteration in the replication timing of this band mainly in Rett patients' cells is particularly interesting as the gene for ornithine transcarbamylase (OTC) which has been previously implicated in studies of Rett syndrome is known to lie within band Xp21 (Hyman & Batshaw 1986, Thomas et al 1987 and the locus for synapsin which has been suggested as a possible candidate gene for Rett syndrome is at Xpll.2 (Ferlini et al 1990). Moreover, both of the translocations reported involving the X-chromosome in Rett patients occurred in the short arm, although the breakpoints were well separated in genetic terms.…”

Section: Discussionmentioning

confidence: 95%

X‐inactivation in girls with Rett syndrome

et al. 1992

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Cytogenetic studies have been carried out on a series of nine girls with Rett syndrome, six of their mothers and nine normal female controls. No abnormality of the X‐chromosome has been observed in any subject. X‐inactivation studies using various methods of detecting the timing of individual band replication were performed. The overall pattern seen was essentially the same in all subjects, but in the patients with Rett syndrome there may be an alteration in the timing of the X‐inactivation process in the region Xp11.3 or 4→Xp21.

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Rett's Syndrome and Ornithine Carbamoyltransferase Deficiency

Cited by 15 publications

References 5 publications

Rett's syndrome and ornithine carbamoyltransferase deficiency

Rett's syndrome and ornithine carbamoyltransferase deficiency

Segregation analysis of the X‐chromosome in a family with rett syndrome in two generations

X‐inactivation in girls with Rett syndrome

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