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'''Ribose-5-phosphate isomerase deficiency''' (RPI deficiency,[http://www.ncbi.nlm.nih.gov/omim/608611 OMIM #608611]) is a human disorder caused by mutations in the [[pentose phosphate pathway]] [[enzyme]] [[Ribose-5-phosphate isomerase]]. With one single diagnosed patient, RPI deficiency is currently thought to be the most rare disease on the world <ref>Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043</ref>.
'''Ribose-5-phosphate isomerase deficiency''' (RPI deficiency,[http://www.ncbi.nlm.nih.gov/omim/608611 OMIM #608611]) is a human disorder caused by mutations in the [[pentose phosphate pathway]] [[enzyme]] [[ribose-5-phosphate isomerase]]. With a single diagnosed patient, RPI deficiency is currently thought to be the rarest disease in the world<ref>Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043</ref>.


The affected boy was born in 1984 diagnosed by [[MRI]] to suffer from a [[white matter]] diasease ( [[leukoencephalopathy]] ) . Analysis of [[SPECT]] profiles indicated an increase in the [[polyol]]s [[arabitol]], [[ribitol]] and [[erithrol]] <ref>van der Knaap MS, Wevers RA, Struys EA, Verhoeven NM, Pouwels PJ, Engelke UF, Feikema W, Valk J, Jakobs C Leukoencephalopathy associated with a disturbance in the metabolism of polyols. Ann Neurol. 1999 Dec;46(6):925-8. PMID: 10589548 </ref>. This discovery lead later to the identification of the disease causing mutations, a premature [[stop codon]] and a [[missense mutations]] in the RPI gene <ref>Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS. Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet. 2004 Apr;74(4):745-51. PMID: 14988808</ref>.
The affected boy was born in 1984 and diagnosed by [[MRI]] as suffering from a [[white matter]] disease ([[leukoencephalopathy]]) . Analysis of [[SPECT]] profiles indicated an increase in the [[polyol]]s [[arabitol]], [[ribitol]] and [[erithrol]]<ref>van der Knaap MS, Wevers RA, Struys EA, Verhoeven NM, Pouwels PJ, Engelke UF, Feikema W, Valk J, Jakobs C Leukoencephalopathy associated with a disturbance in the metabolism of polyols. Ann Neurol. 1999 Dec;46(6):925-8. PMID: 10589548</ref>. This discovery later led to the identification of the disease-causing mutations, a premature [[stop codon]] and a [[missense mutation]] in the RPI gene <ref>Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS. Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet. 2004 Apr;74(4):745-51. PMID: 14988808</ref>.


Since the report of this first case in 1999, no further patients have yet been diagnosed. In the search for an explantation for this rareness, it has been found that this patient suffers from a very seldom allelic combination <ref>Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043</ref>. One allele is a non-functional [[null allele]], the other one encodes for a partially active enzyme. However, in addition, this allele has expression deficits which depends on the [[cell type]]. Therefore, some of the patients cells have a considerably amount of RPI activity, others not.
Since the report of this first case in 1999, no further patients have been diagnosed. In the search for an explanation for this rarity, it has been found that the patient suffers from a seldom-seen allelic combination<ref>Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043</ref>. One allele is a non-functional [[null allele]], while the other encodes for a partially-active enzyme. Furthermore, the partially-functional allele has expression deficits that depend on the [[cell type]] in which it is expressed. Therefore, some of the patient's cells have a considerable amount of RPI activity, whereas others do not.


The molecular cause of the pathology is not fully understood. One hypothesis is, that [[ribose-5-phosphate]] may lack for RNA synthesis, another possibility that the accumulation of D-ribitol and D-arabitol is toxic.
The molecular cause of the pathology is not fully understood. One hypothesis is that [[ribose-5-phosphate]] may lack for RNA synthesis; another possibility is that the accumulation of D-ribitol and D-arabitol may be toxic.


References
References

Revision as of 13:27, 26 July 2010

Ribose-5-phosphate isomerase deficiency (RPI deficiency,OMIM #608611) is a human disorder caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase. With a single diagnosed patient, RPI deficiency is currently thought to be the rarest disease in the world[1].

The affected boy was born in 1984 and diagnosed by MRI as suffering from a white matter disease (leukoencephalopathy) . Analysis of SPECT profiles indicated an increase in the polyols arabitol, ribitol and erithrol[2]. This discovery later led to the identification of the disease-causing mutations, a premature stop codon and a missense mutation in the RPI gene [3].

Since the report of this first case in 1999, no further patients have been diagnosed. In the search for an explanation for this rarity, it has been found that the patient suffers from a seldom-seen allelic combination[4]. One allele is a non-functional null allele, while the other encodes for a partially-active enzyme. Furthermore, the partially-functional allele has expression deficits that depend on the cell type in which it is expressed. Therefore, some of the patient's cells have a considerable amount of RPI activity, whereas others do not.

The molecular cause of the pathology is not fully understood. One hypothesis is that ribose-5-phosphate may lack for RNA synthesis; another possibility is that the accumulation of D-ribitol and D-arabitol may be toxic.

References

  1. ^ Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043
  2. ^ van der Knaap MS, Wevers RA, Struys EA, Verhoeven NM, Pouwels PJ, Engelke UF, Feikema W, Valk J, Jakobs C Leukoencephalopathy associated with a disturbance in the metabolism of polyols. Ann Neurol. 1999 Dec;46(6):925-8. PMID: 10589548
  3. ^ Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS. Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet. 2004 Apr;74(4):745-51. PMID: 14988808
  4. ^ Wamelink MM, Grüning NM, Jansen EE, Bluemlein K, Lehrach H, Jakobs C, Ralser M. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. J Mol Med. 2010, PMID: 20499043
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