Alternative pathway therapy for urea cycle
`disorders
`
`THE UREA CYCL.E
`
`.... lTtfti ..... 1S
`reli:>rtiJied. Within the urea
`
`INBORN ERRORS OF THE UREA
`
`an
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`

`HEPATIC NITROGEN
`POOL
`
`· Phenylbutyrm "'
`
`Phenylbutytyl CoA
`
`""
`
`glutamine
`
`Hippurate
`
`N-ace.lyl ®
`g utamate.,
`I
`
`..
`
`0
`
`r-""'"""-----.:...'Carbamoyl
`phosph~te
`
`Ornithine
`
`Citrulline
`Aspartate-) C) . .
`
`Arginino·
`succinate · ··
`
`, $ ···:fumarate '
`
`t
`
`orotic
`orotidine .· /
`
`Ornithine
`
`,ft···.
`~·0·.· '
`.
`.
`Arginine ,
`.,
`
`·"
`
`J.lnher. Metab. Dis.
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`

`

`NEUROTOXICITY
`
`UREA CYCLE INTERMEDIATES
`
`2. unrmn:me
`3.
`4. All!:tntrlOStiCClllate
`5. tU~~Ulill~lill
`6.
`
`are
`c.ll.~.<irc:<u;;:u, ttl•"~""'l"v ct:eatioe: an aJtc~rDiitnre
`
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`

`F eillet and Leonard
`
`are
`con-
`
`104
`
`TREATMENT
`
`utilize am~m:ainre
`tbat are deficient.
`
`Low-protein •iet ·
`
`A1teruadve
`
`to
`removed by sodium r>erlzo:ilte,
`
`J. Inlier • .Vetab. Di:r. 21
`
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`

`105
`
`sp;lrB~e-llu mou~ benzoate llllJPSllts "'~'""'•''"
`fatty acid oxidation and the
`
`IJ,ITIOL1
`
`!
`
`400
`
`301:1
`
`200
`
`,.,
`' ' '
`'
`
`'
`' I
`r
`'
`
`lllli
`
`11111
`
`14iH
`
`Time of day
`
`J. Inher. Metab. Dis. 21
`
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`

`next compound introduced was
`by
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`

`Alternative pathway therapy
`
`j.llnOI/1
`
`Phenylbutyrate
`-
`-+- Phenylacetate
`_...,__ Benzoate
`
`the
`who do not swallow
`
`J. Jnher. ,'1,( tUJII. fJis. 21
`
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`

`/····
`
`Citrulline
`
`Citrulline
`
`-i
`
`Ornithine •
`
`Ornithine
`
`~#~,... Urea---.
`
`.......
`~;-~ ~- ~....,. Arginine
`
`,
`
`fumarate
`
`utilize an additional
`In .,.. .............. ..,
`in the
`and ornithine is not reformed
`inc>SUIXlmc aciduria there is a
`ar~nn'ine which is converted to ornithine rer,la.~s::
`
`J.lnher. Metab. Dis. 21
`
`Suppl. 1
`
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`

`109
`
`is
`affecled (Maestri et al
`
`CONCLUSIONS
`
`J.lnher. Metab. Dis. 21
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`

`110
`
`F eillet and Leonard
`
`ACKNOWLEDGEMENTS
`The authors thank Dr Anne Green, Mrs Mary-Anne Preece and Ian Sewell for the
`assays of benzoate and phenylbutyrate and Dr Pau1a Nicolaides and Dr Robert
`Surtees for the outcome data of the patients they have studied.
`
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`Kline JJ, Hug G, Schubert WK, Berry H (1981) Arginine deficiency syndrome. Am J Dis
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`Kubota K, Ishizaki T (1991) Dose-dependent pharmacokinetics of benzoic acid following oral
`administration of sodium benzoate to humans. Eur J Clin Pharmacal 41: 363-368.
`Kubota K, Ishizaki T (1993) Effect of single oral dose of sodium benzoate on uceagenesis in
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`111
`
`J,
`
`21
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`