Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia

Maria Steenhof*, Maria Kibæk, Martin J. Larsen, Mette Christensen, Allan Meldgaard Lund, Klaus Brusgaard, Jens Michael Hertz

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Mutations in ALDH18A1 can cause autosomal recessive and dominant hereditary spastic paraplegia and autosomal recessive and dominant cutis laxa. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), which consists of two domains, the glutamate 5-kinase (G5K) and the gamma-glutamyl phosphate reductase (GR5P) domain. The location of the mutations in the gene has influence on whether the amino acid levels are affected. Mutations affecting the G5K domain have previously been found to cause reduced plasma levels of proline, citrulline and arginine, whereas such effect is not seen with mutations affecting the GR5P domain. We present a 19-year old male patient with autosomal recessive spastic paraplegia and compound heterozygosity for two ALDH18A1 mutations, one in each of the P5CS domains. This young man has spastic paraplegia with onset in childhood and temporal lobe epilepsy, but normal levels of proline, ornithine and arginine. To our knowledge, this is the first case with compound heterozygous mutations affecting both P5CS domains, where levels of plasma amino acids have been reported.

Original languageEnglish
JournalNeurogenetics
Volume19
Issue number3
Pages (from-to)145–149
ISSN1364-6745
DOIs
Publication statusPublished - Aug 2018

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Hereditary Spastic Paraplegia
Amino Acids
Mutation
Ligases
Citrulline
Ornithine
Temporal Lobe Epilepsy
Oxidoreductases

Keywords

  • ALDH18A1
  • Compound heterozygosity
  • Hereditary spastic paraplegia type 9
  • P5CS domain

Cite this

@article{55a4c9b6a01e48d491ba6b15d5764456,
title = "Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia",
abstract = "Mutations in ALDH18A1 can cause autosomal recessive and dominant hereditary spastic paraplegia and autosomal recessive and dominant cutis laxa. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), which consists of two domains, the glutamate 5-kinase (G5K) and the gamma-glutamyl phosphate reductase (GR5P) domain. The location of the mutations in the gene has influence on whether the amino acid levels are affected. Mutations affecting the G5K domain have previously been found to cause reduced plasma levels of proline, citrulline and arginine, whereas such effect is not seen with mutations affecting the GR5P domain. We present a 19-year old male patient with autosomal recessive spastic paraplegia and compound heterozygosity for two ALDH18A1 mutations, one in each of the P5CS domains. This young man has spastic paraplegia with onset in childhood and temporal lobe epilepsy, but normal levels of proline, ornithine and arginine. To our knowledge, this is the first case with compound heterozygous mutations affecting both P5CS domains, where levels of plasma amino acids have been reported.",
keywords = "ALDH18A1, Compound heterozygosity, Hereditary spastic paraplegia type 9, P5CS domain",
author = "Maria Steenhof and Maria Kib{\ae}k and Larsen, {Martin J.} and Mette Christensen and Lund, {Allan Meldgaard} and Klaus Brusgaard and Hertz, {Jens Michael}",
year = "2018",
month = "8",
doi = "10.1007/s10048-018-0547-7",
language = "English",
volume = "19",
pages = "145–149",
journal = "Neurogenetics",
issn = "1364-6745",
publisher = "Heinemann",
number = "3",

}

Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia. / Steenhof, Maria; Kibæk, Maria; Larsen, Martin J.; Christensen, Mette; Lund, Allan Meldgaard; Brusgaard, Klaus; Hertz, Jens Michael.

In: Neurogenetics, Vol. 19, No. 3, 08.2018, p. 145–149.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia

AU - Steenhof, Maria

AU - Kibæk, Maria

AU - Larsen, Martin J.

AU - Christensen, Mette

AU - Lund, Allan Meldgaard

AU - Brusgaard, Klaus

AU - Hertz, Jens Michael

PY - 2018/8

Y1 - 2018/8

N2 - Mutations in ALDH18A1 can cause autosomal recessive and dominant hereditary spastic paraplegia and autosomal recessive and dominant cutis laxa. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), which consists of two domains, the glutamate 5-kinase (G5K) and the gamma-glutamyl phosphate reductase (GR5P) domain. The location of the mutations in the gene has influence on whether the amino acid levels are affected. Mutations affecting the G5K domain have previously been found to cause reduced plasma levels of proline, citrulline and arginine, whereas such effect is not seen with mutations affecting the GR5P domain. We present a 19-year old male patient with autosomal recessive spastic paraplegia and compound heterozygosity for two ALDH18A1 mutations, one in each of the P5CS domains. This young man has spastic paraplegia with onset in childhood and temporal lobe epilepsy, but normal levels of proline, ornithine and arginine. To our knowledge, this is the first case with compound heterozygous mutations affecting both P5CS domains, where levels of plasma amino acids have been reported.

AB - Mutations in ALDH18A1 can cause autosomal recessive and dominant hereditary spastic paraplegia and autosomal recessive and dominant cutis laxa. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), which consists of two domains, the glutamate 5-kinase (G5K) and the gamma-glutamyl phosphate reductase (GR5P) domain. The location of the mutations in the gene has influence on whether the amino acid levels are affected. Mutations affecting the G5K domain have previously been found to cause reduced plasma levels of proline, citrulline and arginine, whereas such effect is not seen with mutations affecting the GR5P domain. We present a 19-year old male patient with autosomal recessive spastic paraplegia and compound heterozygosity for two ALDH18A1 mutations, one in each of the P5CS domains. This young man has spastic paraplegia with onset in childhood and temporal lobe epilepsy, but normal levels of proline, ornithine and arginine. To our knowledge, this is the first case with compound heterozygous mutations affecting both P5CS domains, where levels of plasma amino acids have been reported.

KW - ALDH18A1

KW - Compound heterozygosity

KW - Hereditary spastic paraplegia type 9

KW - P5CS domain

U2 - 10.1007/s10048-018-0547-7

DO - 10.1007/s10048-018-0547-7

M3 - Journal article

C2 - 29754261

AN - SCOPUS:85046815891

VL - 19

SP - 145

EP - 149

JO - Neurogenetics

JF - Neurogenetics

SN - 1364-6745

IS - 3

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