Abstract: PUB306
Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramp (HANAC) Syndrome: There Is More to Explore!
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Baigam, Nahida, LSU Health New Orleans, New Orleans, Louisiana, United States
- Mohandas, Rajesh, LSU Health New Orleans, New Orleans, Louisiana, United States
- Bajracharya, Siddhartha Darshan, LSU Health New Orleans, New Orleans, Louisiana, United States
Introduction
Structural integrity of the glomerular basement membrane (GBM) is essential to maintain the selectivity of the slit diaphragm and filtration barrier. One of the key components of the GBM is Collagen Type 4. Mutations in Collagen Type 4 underlie the well-known hereditary disorder, Alport’s syndrome. We report a more uncommon hereditary disorder affecting the kidneys due to mutations in Collagen Type 4
Case Description
A 30-year-old man with bilateral congenital cataracts and cerebral palsy (CP)was referred for asymptomatic microscopic hematuria. He did not report muscle pain or cramps, neurological symptoms, gross hematuria, hearing issues, polydipsia, or polyuria. He had hypertension but was not on medications. His estimated Glomerular filtration has declined from 66 to 57 mL/min/1.73m2. Otherwise, his lab work was within normal limits. He did not have a family history of CKD, but his mother and sister had CP. We performed a renal biopsy, which showed Thin Glomerular Basement Membrane Disease (TBMN) and genetic test was performed, which revealed a pathogenic mutation in COL4α1.
Discussion
The glomerular basement membrane in humans contains two separate networks of type 4 collagen. The sub-endothelial GBM comprised of α1/α2 networks, while the thicker sub-epithelial layer comprised of α3/α4/α5 networks. Defects in α3/α4/α5 cause Alport’s syndrome, while mutations in COL4α1 mutations can cause diverse clinical presentations hereditary angiopathy with nephropathy, aneurysms, and muscle cramps, the HANAC syndrome, and non-syndromic congenital cataracts. Renal involvement can cause thin basement membrane with microscopic hematuria and renal cysts and less often CKD. Earlier genetic testing could have avoided the need for a biopsy in this patient.
Worldwide, 13.4% of the population has CKD; among the causes, Primary glomerular disease is more than 8% and familial 10%. COL4 A disorders have significant similarities. All patients with suspected Alport syndrome or TBMN disease should receive genetic testing for the COL4 variants because up to 27% of cases are caused by a de novo pathogenic variant. The penetrance of COL4A1-related disorders is close to 100%, with the clinical presentation differing widely. Genetic testing allows for the early detection of exceptionally rare kidney diseases like HANAC syndrome.