A novel missense HGD gene mutation, K57N, in a patient with alkaptonuria

Clin Chim Acta. 2009 May;403(1-2):254-6. doi: 10.1016/j.cca.2009.03.032. Epub 2009 Mar 21.

Abstract

Alkaptonuria is a rare recessive disorder of phenylalanine/tyrosine metabolism due to a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) caused by mutations in the HGD gene. We report the case of a 38 year-old male with known alkaptonuria who was referred to an adult metabolic clinic after initially presenting to an emergency department with renal colic and subsequently passing black ureteric calculi. He complained of severe debilitating lower back pain, worsening over the last few years. A CT scan revealed marked degenerative changes and severe narrowing of the disc spaces along the entire lumbar spine. Sequencing of the HGD gene revealed that he was a compound heterozygote for a previously described missense mutation in exon 13 (G360R) and a novel missense mutation in exon 3 (K57N). Lys(57) is conserved among species and mutation of this residue is predicted to affect HGD protein function by interfering with substrate traffic at the active site. In summary, we describe an alkaptonuric patient and report a novel missense HGD mutation, K57N.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alkaptonuria / diagnostic imaging
  • Alkaptonuria / genetics*
  • Alkaptonuria / pathology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Homogentisate 1,2-Dioxygenase / chemistry
  • Homogentisate 1,2-Dioxygenase / genetics*
  • Humans
  • Male
  • Models, Molecular
  • Mutation, Missense*
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Tomography, X-Ray Computed

Substances

  • Homogentisate 1,2-Dioxygenase