Abstract: SA-PO593
COL4A1 Mutation: Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps (HANAC) Syndrome, an ADPKD Mimicker
Session Information
- Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Fichadiya, Harshil, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Patel, Vraj, Canton Medical Education Foundation, Canton, Ohio, United States
- Bentall, Andrew J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Introduction
Type 4 collagen(T4C) has 6 alpha subunits(A1-6) and is responsible for synthesis of most basement membranes. Alport syndrome involving defect in synthesis of A5 and rarely A3/A4 subnits is the most common known genetic syndrome resulting from faulty T4C synthesis. While A3,4,5 collagen network replaces A1,1,2 network during embryogenesis in the GBM, A1,1,2 network is the most common network in Bowmans space, tubular BM, rest of the body, including blood vessels
HANAC syndrome (Heridetary Angiopathy, Nephropathy, Aneurysm and Muscle Cramps) has been described with AD inheritance in families with defective A1 subunit synthesis. Kidney disease is characterized by mild hematuria and renal cyst. Emmanuelle etal characterized phenotypes from 3 families having HANAC syndrome and reported glycine mutation in exon 24 and exon 25
Case Description
74 year old female referred for evaluation of preemptive kidney transplant. She first presented with microhematuria and was first diagnosed with CKD at age 30. CKD progressed gradually over multiple years to stage 4 CKD in 2023. She has persistent microhematuria and proteinururia has gradually progressed to 1.5g/24hrs, reported strong family history of PKD in aunts, uncles and cousins. Multiple USG over the years revealed small kidneys with 2-3 partially regressing cyst bilaterally, largest cyst 3cm. Genetic analysis using next generation sequencing revealed mutation in COL4A1 gene. She described experiency occasional muscle cramps. MRA revealed 3 mm right and left ICA aneursyms She is listed for DDKT
Discussion
Since most ADPKD cases are diagnosed based on imaging criteria and positive family history when available, COL4A1 mutation can be easily confused for ADPKD when genetic testing is not performed. It is important to make this distinction as specific therapies available for ADPKD may not be as effective in patients with COL4A1 mutation. HANAC syndrome is a rare genetic syndrome characterized by cystic kidney disease aneurysm involving mutiple organ systems & retinal vessel (vs mainly CNS in ADPKD), cardiac, and muscular abnormalities causing cramping and occasionally hypotonia with developmental delay. Additionally digenic genotype with both COL4A1-PKD mutation have been identified with earlier progress to ESRD,50 years age. Our case presented with small kidneys,hematuria, 2-3 renal cyst and mild CNS aneurysms with ocassional cramping and slow progression