A novel pathogenic variant in LCAT causing FLD. A case report

ABSTRACT

Background

Fish-eye disease (FED) is due to a partial deficiency in LCAT activity. Nevertheless, Familial lecithin-cholesterol acyltransferase deficiency (FLD), also called Norum disease, appears when the deficiency is complete. They are both rare genetic disorders inherited in an autosomal recessive manner. Clinical signs include decreased circulating HDL cholesterol and dense corneal opacity. Kidney injuries also affect patients suffering from FLD. The diagnosis of FLD is based on the presence of characteristic signs and symptoms and confirmed by genetic testing.

Case presentation

We present a case of a 63-year-old man showing an altered lipid profile with low HDL cholesterol, chronic kidney disease (CKD) and corneal disorders. He was referred to genetic counseling in order to discard genetic LCAT deficiency due to decreased visual acuity caused by corneal opacity. A massive DNA sequencing was conducted using a multigene panel associated with lipid metabolism disturbances.

Results and genetic findings

Two likely pathogenic variants in LCAT were identified and later confirmed by Sanger sequencing. Both (c.491 G > A and c.496 G > A) were missense variants that originated an amino acid substitution (164Arginine for Histidine and 166Alanine for Threonine, respectively) modifying the protein sequence and its 3D structure.

Conclusions

FLD and FED sharing common biochemical features, and the existence of other diseases with similar clinical profiles underline the need for a timely differential diagnosis aiming to address patients to preventive programs and future available therapies. This case, added to the reduced number of publications previously reported regarding FLD and FED, contributes to better understanding the genetic characteristics, clinical features, and diagnosis of these syndromes.

KEYWORDS:

• Lecithin-cholesterol acyltransferase deficiency
• Norum disease
• fish-eye disease
• HDL
• LCAT
• corneal opacity

Acknowledgments

To the patients and parents.

Authors’ contributions

NGR, RGT, PSB and ESR drafted and critically reviewed the manuscript with literature research. MPB and JPF were the principal physicians in patient’s cases. All authors read and approved the final manuscript.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Consent for publication

Written informed consent was obtained from the patient for publication of case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Disclosure statement

No potential conflict of interest was reported by the author.