A novel α-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease

David Rosenthal, Yeong Hau H Lien, Donna Lager, Li Wen Lai, Shuhua Shang, Nelson Leung, Fernando Custodio Fervenza

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A 65-year-old man presented to our institution for workup of proteinuria. His serum creatinine level was 1.7 mg/dL (130 μmol/L), and he had proteinuria with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney biopsy and low serum and leukocyte levels of α-galactosidase A. Review of his history, family history, physical examinations, and diagnostic studies did not show other findings typical of this disease. His renal function continued to decline, and he eventually underwent a living unrelated renal transplantation 5 years later. Three years after transplantation, his creatinine level is 1.7 mg/dL (130 μmol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m 2. Genetic studies showed that he has a novel missense mutation (M42L) in exon 1. Methionine at codon 42 is highly conserved in eukaryotic α-galactosidase A orthologues. This genotype predicts a minor misfolding of α-galactosidase A because of a small difference in hydrophobicity between methionine and leucine. His mutation resulted in a very low, but detectable, serum level of α-galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry disease that present with predominantly renal manifestations are rare and require a high index of suspicion for diagnosis. Because treatment for Fabry disease recently has become available, it is important for clinicians to be aware of this disease and pursue the diagnosis in cases of otherwise unexplained renal dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
Volume44
Issue number5
DOIs
StatePublished - Nov 2004

Fingerprint

Galactosidases
Fabry Disease
Kidney
Proteinuria
Methionine
Creatinine
Serum
Iothalamic Acid
Missense Mutation
Hydrophobic and Hydrophilic Interactions
Codon
Leucine
Kidney Transplantation
Physical Examination
Exons
Reference Values
Leukocytes
Transplantation
History
Genotype

Keywords

  • α-galactosidase A
  • Fabry disease
  • genotype
  • mutation analysis
  • phenotype

ASJC Scopus subject areas

  • Nephrology

Cite this

A novel α-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease. / Rosenthal, David; Lien, Yeong Hau H; Lager, Donna; Lai, Li Wen; Shang, Shuhua; Leung, Nelson; Fervenza, Fernando Custodio.

In: American Journal of Kidney Diseases, Vol. 44, No. 5, 11.2004.

Research output: Contribution to journalArticle

Rosenthal, David ; Lien, Yeong Hau H ; Lager, Donna ; Lai, Li Wen ; Shang, Shuhua ; Leung, Nelson ; Fervenza, Fernando Custodio. / A novel α-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease. In: American Journal of Kidney Diseases. 2004 ; Vol. 44, No. 5.
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