276:
abnormality. A third case was reported in 2018 by
Sklower Brooks and colleagues, a child with neonatal onset leukoencephalopathy and psychomotor delays. A fourth case was reported in 2019 by Kaur and colleagues with progressive leukoencephalopathy and elevated urine polyols arabitol and ribitol.
228:
The first patient was a male born in 1984 to healthy, unrelated parents. Early in life, the patient had psychomotor retardation and developed epilepsy at age 4. From age 7, a slow neurological regression occurred with prominent
549:
Wang, Ching-Tzu; Chen, Yi-Chun; Wang, Yi-Yun; Huang, Ming-Hao; Yen, Tzu-Li; Li, Hsun; Liang, Cyong-Jhih; Sang, Tzu-Kang; Ciou, Shih-Ci; Yuh, Chiou-Hwa; Wang, Chao-Yung; Brummel, Theodore J.; Wang, Horng-Dar (February 2012).
751:
van der Knaap MS, Wevers RA, Struys EA, Verhoeven NM, Pouwels PJ, Engelke UF, Feikema W, Valk J, Jakobs C (December 1999). "Leukoencephalopathy associated with a disturbance in the metabolism of polyols".
256:
In 1999 van der Knaap and colleagues reviewed this case of the then 14-year-old boy and characterised the associated symptoms of RPI deficiency as the following: developmental delay, insidious
795:
Naik N, Shah A, Wamelink MC, van der Knaap MS, Hingwala D (September 2017). "Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy".
552:"Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila"
208:
RPI can be diagnosed by gene sequencing or increased polyol levels in blood or urine. Patients also present highly elevated polyols in the brain, which can be revealed by
504:"Polyols accumulated in ribose-5-phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats' prefrontal cortex"
230:
63:
696:"Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy"
644:"Ribose-5-phosphate isomerase deficiency: New inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy"
408:"Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy"
838:
Brooks SS, Anderson S, Bhise V, Botti C (October 2018). "Further
Delineation of Ribose-5-phosphate Isomerase Deficiency: Report of a Third Case".
245:
dysfunction of internal organs. MRI scans at age 11 and 14 revealed extensive abnormalities of the cerebral white matter and elevated levels of
161:. Artificial downregulation of RPI has been therefore suggested as a treatment against disease caused by polyglutamine neutroxicity (such as
153:
Paradoxically, downregulation of ribose-5-phosphate isomerase in
Drosophila melanogaster leads to a fitter phenotype: enhanced tolerance to
694:
Huck, Jojanneke H. J.; Verhoeven, Nanda M.; Struys, Eduard A.; Salomons, Gajja S.; Jakobs, Cornelis; van der Knaap, Marjo S. (April 2004).
90:
in which it is expressed. Therefore, some of the patient's cells have a considerable amount of RPI activity, whereas others do not.
209:
125:
model and concluded that the accumulation of polyols has likely only a secondary effect on brain dysfunction, if any at all.
765:
324:"The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency"
150:
content in the rat prefrontal cortex. Additionally, neither polyol influenced the oxidation levels of proteins or lipids.
955:
379:
146:
was increased under the influence of ribitol, while arabitol showed no such effect. Neither polyol had any impact on the
881:
Kaur, Parneet; Wamelink, Mirjam M.C.; Van Der Knaap, Marjo S.; Girisha, Katta Mohan; Shukla, Anju (2019-08-01).
323:
139:
production was elevated with the addition of ribitol, but not with arabitol. Furthermore, the activity of three
619:"Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials"
328:
995:
322:
Wamelink, M. M.; GrĂĽning, N. M.; Jansen, E. E.; Bluemlein, K.; Lehrach, H.; Jakobs, C.; Ralser, M. (2010).
268:
and abnormal polyol metabolism. Later, Naik and colleagues reported a second case, an 18-year-old man with
47:
882:
82:, while the other encodes for a partially active enzyme. Furthermore, the partially functional allele has
642:
Huck, J. H.; Verhoeven, N. M.; Struys, E. A.; Salomons, G. S.; Jakobs, C.; Van Der Knaap, M. S. (2004).
618:
202:
74:
In the search for an explanation for this rarity, it has been found that the patient has a seldom-seen
503:
55:
966:
194:
162:
456:
1017:
883:"Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA"
8:
265:
198:
606:
406:
Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS (April 2004).
220:
There is no current treatment or prognosis for ribose-5-phosphate isomerase deficiency.
918:
863:
820:
777:
728:
695:
668:
643:
584:
551:
455:
Klusmann, A.; Fleischer, W.; Waldhaus, A.; Siebler, M.; Mayatepek, E. (December 2005).
432:
407:
360:
94:
922:
910:
902:
855:
812:
769:
733:
715:
673:
589:
571:
567:
531:
523:
484:
476:
437:
352:
182:
129:
93:
The molecular cause of the pathology is not fully understood. One hypothesis is that
867:
781:
364:
894:
847:
824:
804:
761:
723:
707:
663:
655:
579:
563:
519:
515:
468:
427:
419:
344:
336:
154:
58:. With four diagnosed patients over a 27-year period, RPI deficiency is the second
971:
808:
83:
66:
being the rarest, affecting two known individuals, Catherine and
Kirstie Fields.
502:
Stone, V.; Kudo, K.Y.; August, P.M.; Marcelino, T.B.; Matté, C. (October 2014).
898:
472:
340:
1011:
906:
851:
719:
575:
527:
480:
234:
174:
133:
98:
914:
859:
816:
773:
737:
677:
593:
535:
488:
441:
356:
273:
242:
59:
257:
147:
140:
79:
947:
238:
190:
136:
348:
178:
122:
87:
380:"These twins are 'trapped' in their living room as work plans stall"
990:
766:
10.1002/1531-8249(199912)46:6<925::aid-ana18>3.0.co;2-j
711:
659:
457:"Influence of D -arabitol and ribitol on neuronal network activity"
423:
261:
186:
114:
750:
295:"OMIM Entry - # 608611 - Ribose 5-Phosphate Isomerase Deficiency"
269:
117:
may be toxic. However, Klussman et al. evaluated the toxicity of
106:
75:
960:
880:
454:
16:
Rare metabolic genetic disorder resulting in leukoencephalopathy
294:
158:
143:
118:
51:
321:
794:
693:
641:
405:
837:
501:
607:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257417/
937:
508:
International
Journal of Developmental Neuroscience
101:. Another possibility is that the accumulation of
46:) is a rare human disorder caused by mutations in
548:
1009:
689:
687:
401:
399:
831:
788:
744:
684:
396:
78:combination. One allele is a nonfunctional
317:
315:
727:
667:
583:
431:
165:) but also to counteract normal ageing.
377:
312:
40:Ribose-5-phosphate isomerase deficiency
25:Ribose-5-phosphate isomerase deficiency
1010:
461:Journal of Inherited Metabolic Disease
210:proton magnetic resonance spectroscopy
272:, psychomotor regression and diffuse
887:European Journal of Medical Genetics
13:
700:American Journal of Human Genetics
648:American Journal of Human Genetics
412:American Journal of Human Genetics
14:
1029:
933:
568:10.1111/j.1474-9726.2011.00762.x
874:
635:
611:
600:
542:
520:10.1016/j.ijdevneu.2014.06.009
495:
448:
378:Dalling, Robert (2017-02-10).
371:
287:
1:
280:
809:10.1212/WNL.0000000000004361
215:
168:
86:deficits that depend on the
69:
48:ribose-5-phosphate isomerase
7:
10:
1034:
899:10.1016/j.ejmg.2019.103708
840:Journal of Child Neurology
237:, and a mild sensorimotor
223:
203:global developmental delay
981:
941:
473:10.1007/s10545-005-0073-2
341:10.1007/s00109-010-0634-1
56:pentose phosphate pathway
29:
24:
852:10.1177/0883073818789316
97:may be insufficient for
195:psychomotor retardation
62:known as of now, with
163:Huntington's disease
754:Annals of Neurology
266:leukoencephalopathy
233:, some spasticity,
199:leukoencephalopathy
982:External resources
95:ribose-5-phosphate
1005:
1004:
803:(11): 1195–1196.
623:www.malacards.org
252:
248:
241:with no observed
231:cerebellar ataxis
183:cerebellar ataxia
173:Symptoms include
159:extended lifespan
130:prefrontal cortex
112:
104:
37:
36:
19:Medical condition
1025:
939:
938:
927:
926:
878:
872:
871:
835:
829:
828:
792:
786:
785:
748:
742:
741:
731:
691:
682:
681:
671:
639:
633:
632:
630:
629:
615:
609:
604:
598:
597:
587:
546:
540:
539:
499:
493:
492:
467:(6): 1181–1183.
452:
446:
445:
435:
403:
394:
393:
391:
390:
375:
369:
368:
319:
310:
309:
307:
305:
291:
250:
246:
155:oxidative stress
110:
102:
64:Fields condition
22:
21:
1033:
1032:
1028:
1027:
1026:
1024:
1023:
1022:
1008:
1007:
1006:
1001:
1000:
977:
976:
950:
936:
931:
930:
879:
875:
846:(12): 784–787.
836:
832:
793:
789:
749:
745:
692:
685:
640:
636:
627:
625:
617:
616:
612:
605:
601:
547:
543:
500:
496:
453:
449:
404:
397:
388:
386:
376:
372:
320:
313:
303:
301:
293:
292:
288:
283:
226:
218:
171:
72:
20:
17:
12:
11:
5:
1031:
1021:
1020:
1003:
1002:
999:
998:
986:
985:
983:
979:
978:
975:
974:
963:
951:
946:
945:
943:
942:Classification
935:
934:External links
932:
929:
928:
873:
830:
787:
743:
712:10.1086/383204
706:(4): 745–751.
683:
660:10.1086/383204
654:(4): 745–751.
634:
610:
599:
541:
494:
447:
424:10.1086/383204
395:
370:
311:
285:
284:
282:
279:
225:
222:
217:
214:
170:
167:
71:
68:
60:rarest disease
35:
34:
33:RPI deficiency
31:
27:
26:
18:
15:
9:
6:
4:
3:
2:
1030:
1019:
1018:Rare diseases
1016:
1015:
1013:
997:
993:
992:
988:
987:
984:
980:
973:
969:
968:
964:
962:
958:
957:
953:
952:
949:
944:
940:
924:
920:
916:
912:
908:
904:
900:
896:
893:(8): 103708.
892:
888:
884:
877:
869:
865:
861:
857:
853:
849:
845:
841:
834:
826:
822:
818:
814:
810:
806:
802:
798:
791:
783:
779:
775:
771:
767:
763:
759:
755:
747:
739:
735:
730:
725:
721:
717:
713:
709:
705:
701:
697:
690:
688:
679:
675:
670:
665:
661:
657:
653:
649:
645:
638:
624:
620:
614:
608:
603:
595:
591:
586:
581:
577:
573:
569:
565:
562:(1): 93–103.
561:
557:
553:
545:
537:
533:
529:
525:
521:
517:
513:
509:
505:
498:
490:
486:
482:
478:
474:
470:
466:
462:
458:
451:
443:
439:
434:
429:
425:
421:
418:(4): 745–51.
417:
413:
409:
402:
400:
385:
381:
374:
366:
362:
358:
354:
350:
346:
342:
338:
335:(9): 931–39.
334:
331:
330:
325:
318:
316:
300:
296:
290:
286:
278:
275:
271:
267:
263:
259:
254:
249:-ribitol and
244:
240:
236:
235:optic atrophy
232:
221:
213:
211:
206:
204:
200:
196:
192:
188:
184:
180:
176:
175:optic atrophy
166:
164:
160:
156:
151:
149:
145:
142:
138:
135:
134:mitochondrial
131:
126:
124:
120:
116:
108:
100:
99:RNA synthesis
96:
91:
89:
85:
81:
77:
67:
65:
61:
57:
53:
49:
45:
41:
32:
28:
23:
989:
965:
954:
890:
886:
876:
843:
839:
833:
800:
796:
790:
760:(6): 925–8.
757:
753:
746:
703:
699:
651:
647:
637:
626:. Retrieved
622:
613:
602:
559:
555:
544:
514:(1): 21–25.
511:
507:
497:
464:
460:
450:
415:
411:
387:. Retrieved
383:
373:
332:
329:J. Mol. Med.
327:
302:. Retrieved
298:
289:
274:white matter
260:regression,
255:
243:organomegaly
227:
219:
207:
172:
152:
127:
92:
73:
43:
39:
38:
384:WalesOnline
258:psychomotor
253:-arabitol.
148:glutathione
141:antioxidant
80:null allele
30:Other names
628:2018-03-05
556:Aging Cell
389:2021-07-31
349:1871/34686
281:References
239:neuropathy
191:spasticity
137:superoxide
84:expression
923:195760193
907:1769-7212
797:Neurology
720:0002-9297
576:1474-9718
528:0736-5748
481:0141-8955
216:Treatment
179:nystagmus
169:Diagnosis
123:neurochip
121:on a rat
88:cell type
70:Mechanism
1012:Category
991:Orphanet
915:31247379
868:51936427
860:30088433
817:28801340
782:43743595
774:10589548
738:14988808
678:14988808
594:22040003
536:24970317
489:16435225
442:14988808
365:10870492
357:20499043
304:16 March
299:omim.org
270:seizures
262:epilepsy
187:seizures
115:arabitol
972:C563212
825:9554949
729:1181951
669:1181951
585:3257417
433:1181951
224:History
144:enzymes
128:In rat
119:polyols
107:ribitol
76:allelic
54:of the
996:440706
961:608611
921:
913:
905:
866:
858:
823:
815:
780:
772:
736:
726:
718:
676:
666:
592:
582:
574:
534:
526:
487:
479:
440:
430:
363:
355:
52:enzyme
919:S2CID
864:S2CID
821:S2CID
778:S2CID
361:S2CID
50:, an
967:MeSH
956:OMIM
911:PMID
903:ISSN
856:PMID
813:PMID
770:PMID
734:PMID
716:ISSN
674:PMID
590:PMID
572:ISSN
532:PMID
524:ISSN
485:PMID
477:ISSN
438:PMID
353:PMID
306:2019
201:and
157:and
109:and
44:RPID
895:doi
848:doi
805:doi
762:doi
724:PMC
708:doi
664:PMC
656:doi
580:PMC
564:doi
516:doi
469:doi
428:PMC
420:doi
345:hdl
337:doi
1014::
994::
970::
959::
917:.
909:.
901:.
891:62
889:.
885:.
862:.
854:.
844:33
842:.
819:.
811:.
801:89
799:.
776:.
768:.
758:46
756:.
732:.
722:.
714:.
704:74
702:.
698:.
686:^
672:.
662:.
652:74
650:.
646:.
621:.
588:.
578:.
570:.
560:11
558:.
554:.
530:.
522:.
512:37
510:.
506:.
483:.
475:.
465:28
463:.
459:.
436:.
426:.
416:74
414:.
410:.
398:^
382:.
359:.
351:.
343:.
333:88
326:.
314:^
297:.
264:,
212:.
205:.
197:,
193:,
189:,
185:,
181:,
177:,
132:,
948:D
925:.
897::
870:.
850::
827:.
807::
784:.
764::
740:.
710::
680:.
658::
631:.
596:.
566::
538:.
518::
491:.
471::
444:.
422::
392:.
367:.
347::
339::
308:.
251:D
247:D
113:-
111:D
105:-
103:D
42:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.