Abstract: PUB298
Fumarate Hydratase-Deficient Renal Cell Carcinoma
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Author
- Khater, Emad S., SehaKidney Care, Abu Dhabi, Abu Dhabi, United Arab Emirates
Introduction
Fumarate hydratase FH deficiency is very rare disorder. characterized by educed FH enzyme activity .Fumarate hydratase-deficient renal cell carcinoma RCC is a rare pathological subtype.
Case Description
We reported a 33 years old male know to have diabetes and hypertension well controlled .presented with complains of right side loin pain. and visible haematuria . no family history or renal disease.renal function normal. Urine showed RBC. Clinical examination unremarkable.
CT showed large infiltrating tumour in the right kidney. biopsy of renal mass showed renal RCC .However, as the patient is young. translocation related tumours considered hence immunohistochemistry performed it showed diagnosis of a fumarate hydratase-deficient RCC. plan was to start the patient on immunotherapy in the form bevacizumab and erlotinib and to repeat the CT if CT improved then to do nephrectomy.
Discussion
Fumarate catalysed to malet by fumarate FH enzyme in Krebs cycles.deficiency of FH enzyme due to Genetic disorder lead to accumulation fumarate intracellularly and extracellularly. Its rare disorder. mode of transmission is autosomal recessive.accumulation of fumarate may function as an oncometabolite .in homozygous FH deficiency causes sever neonatal neurological defect ,dysmorphic feature and brain abnormalities.prognosis is poor most of severely affected child do not survive .The heterozygotes form majority of cases are healthy.however,they may develop tumours like cutaneous leiomyomata uterine fibroids and uterine myomas also may develop RCC known as Hereditary Leiomyomatosis with Renal Cell carcinoma HLRCC .In regards to RCC associated with FH deficiency defined as a rare pathological subtype (WHO 5th edition 2022) .due to mutations in the FH gene. Diagnosed based on a molecular and immunohistochemical biomarkers.The incidence is very rare and only a few hundreds of cases reported.average age onset between 20 -25. Unfortunately its highly metastasize and very invasive. main treatment is nephrectomy. immunotherapy considered new hope in these patients treatment.Family member of high risk needs early genetic counselling and testing also renal surveillance.Conclusion ,FH deficiency is an autosomal recessive disease .due to accumulation of fumarate. It may associated with RCC FH deficient. Its rare disease very invasive .in young age with RCC advised to investigate for FH deficiency as possible cause.