|Year : 2013 | Volume
| Issue : 4 | Page : 432-435
Gross hematuria with tuberous sclerosis: Case report and review of literature
Sunder Sunde1, Yogendra B Agarwal2, Sham Singla3, Snigdha Goyal4
1 Department of Surgery, Muzaffarnagar Medical College, Uttar Pradesh, India
2 Department of Medicine, Muzaffarnagar Medical College, Uttar Pradesh, India
3 Department of Surgery, Pt BD Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
4 Department of Pathology, Dr. RML Post Graduate Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||17-Sep-2013|
Department of Surgery, Muzaffarnagar Medical College, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Tuberous sclerosis complex is a genetic (autosomal dominant) disorder affecting cellular differentiation, proliferation, and maturation. This cellular process gets disarranged and results in hamartomas formation in multiple organs of body including, the kidneys. Kidney involvement is usually bilateral and asymptomatic. We report a case of bilateral renal angiomyolipomas who presented at late age with gross hematuria and pain.
Keywords: Angiomyolipoma, hamartomas, tuberous sclerosis complex
|How to cite this article:|
Sunde S, Agarwal YB, Singla S, Goyal S. Gross hematuria with tuberous sclerosis: Case report and review of literature. Med J DY Patil Univ 2013;6:432-5
|How to cite this URL:|
Sunde S, Agarwal YB, Singla S, Goyal S. Gross hematuria with tuberous sclerosis: Case report and review of literature. Med J DY Patil Univ [serial online] 2013 [cited 2019 Dec 16];6:432-5. Available from: http://www.mjdrdypu.org/text.asp?2013/6/4/432/118275
| Introduction|| |
Tuberous sclerosis complex (TSC) (Bourneville's disease) is uncommon clinical entity. Incidence of tuberous sclerosis is increasing. It was 1:150000 in 1956 and progressively increased to 1:1, 25,000 in 1998. It is characterized by the presence of hamartomas in various organs of body such as skin, brain, heart, kidney, lung, and bone. Its main clinical triad includes, mental retardation, seizures, and facial angiofibromas.  Angiomyolipomas (AMLs) and renal cysts are the common renal anomalies in TSC. Incidence of renal AML is 50-80% and that of cyst is about 18-53% and for both is 12-27%. ,, The radiological hallmarks of this neurocutaneous syndrome are universally accepted as sufficient for diagnosis.  Spontaneous hemorrhage (wonderlich syndrome) or compression can occur due to renal lesions but end-stage renal failure due renal AML is very rare.  AMLs, which develops aneurysm are more prone to cause severe hemorrhage. We describe a patient of TSC with bilateral renal AMLs, who presented with pain and spontaneous macroscopic hematuria. This case is worth reporting as, this patient did not have any clinical neurological symptoms as well as presented very late in life.
| Case Report|| |
A 32-year-old female presented in out-patient department with history of gross hematuria and pain in right lumbar region. On examination, there was tenderness at right renal without any lump. Patient was investigated for hematuria with ultrasound and contrast enhanced computed tomography abdomen, which revealed hyperechoic lesions with same density as renal sinus fat tissue within the right and left renal parenchyma diagnosed as bilateral renal AML (bigger on right side) and left renal cyst [Figure 1]. Routine urine analysis reported multiple red blood cells. Magnetic resonance imaging (MRI) was performed to confirm or to rule out tuberous sclerosis as there is high incidence of TSC (50-80%) in patients of bilateral AMLs and renal cyst lesions. ,,, To our great surprise, it turned out a case of tuberous sclerosis with typical tuberous lesions on MRI [Figure 2]. Further, fundus examination of eye also revealed retinal achromic patch [Figure 3]. Considering all investigations, patient was diagnosed clinically as a case of tuberous sclerosis. Patient is neither mentally retarded nor having any history of seizures. There is no family history of this disease and also her both children do not have any complaint. There was no history of aggressive behavior or self-injurious behavior in the patient. Genetic screening is positive in approximately 80% cases and is very costly test and moreover, our diagnosis was confirmed with MRI henc, we did not ask for genetic screening. Patient was advised admission for embolization but she refused and lost the follow-up.
|Figure 1: Contrast enhanced computed tomography abdomen showing bilateral angiomyolipomas with renal cyst on left side|
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| Discussion|| |
Uniqueness about this case is that this case of TSC presented at very late age with hematuria without any neurological signs and symptoms. There are no signs and symptoms in her both children as well as there is no family history but TSC is a genetic disorder which present at early age and is usually accompanied by triad of mental retardation, seizures, and facial angiofibromas.
Tuberous sclerosis is a genetic disorder with an autosomal dominant pattern of inheritance, and penetrance is variable.  Two-thirds of TSC cases result from sporadic genetic mutations, not inheritance, however, their offspring may inherit it from them. Current genetic tests have difficulty in locating the mutation in approximately 20% of individuals diagnosed with the disease.In TSC, the inheritance is autosomal dominant, while up to 50-70% of cases of TSC have been attributed to new mutations. So far, two genetic loci have been identified. The first gene maps to chromosome 9 specifically 9q34 (TSC1); the second gene maps to chromosome 16, specifically 16p13 (TSC2). If, Tuberin (the protein-gene product of TSC2) and hamartin (the protein-gene product of TSC1) do not function synergistically, formation of hamartomas may result, which resemble embryonic cells, suggesting that the defects appears at an early stage of life. 
Most of the TSC patients can be diagnosed clinically due to typical triad of fascial nevus, seizures, and mental retardation. Sometime a clear diagnosis cannot be made on clinical finding alone, and then genetic screening testing is useful. It helps (1) confirmation of diagnosis made on clinical grounds; (2) carrier testing for other at-risk family members; and (3) prenatal diagnosis (4) where it is difficult for individual (newborn) to go through imaging studies required for the clinical diagnosis.
However, clinical genetic test identifies approximately 80% of the mutations in samples that are submitted for testing from individuals who have a definite diagnosis of TSC. In the rest 20% of the cases, the mutation is not detectable. This is a very costly test and facilities for this test are limited even in developed countries. In addition, this test has got social, legal, and ethical dilemma. So, this patient was not asked for genetic screening.
In 1880, Désiré-Magloire Bourneville was first to describe these tuber; and these cortical manifestations are still known by the eponym Bourneville's disease. The physical manifestations of tuberous sclerosis are due to the formation of hamartia (malformed tissue such as the cortical tubers), hamartomas (benign growths such as facial angiofibromas and subependymal nodules) and very rarely, cancerous hamartoblastomas. Tuberous sclerosis, the second most common neurocutaneous syndrome, is characterized by a constellation of major and minor features. Major features include facial angiofibromas, non-traumatic ungula or peri-ungual fibromas, hypomelanotic macules, shagreen patch, retinal hamartomas, cortical tubers, subependymal nodule, subependymal giantcell astrocytoma, cardiacrhabdomyoma, lymphangiomyomatosis, and renal AML. Minor features include, dental enamel pits, hamartomatous rectal polyps, bone cysts, gingival fibromas, non-renal hamartomas, retinal achromic patch, confetti skin lesions, renal cysts, and cerebral cortical dysplasia.
Various neurological symptoms are seizures, developmental delay, and behavioral problems. Incidence of learning difficulties is in about 50-60% of people with TSC and reported incidence of autism is between 25% and 60% of affected individuals, with an even higher proportion showing features of a broader pervasive developmental disorder. Reported incidence of self-injurious behavior is about 10% of people with TSC. Other conditions, such as Attention Defeciet Hyperactivity Disorder (ADHD), aggression, behavioral outbursts, and Obsessive Compulsive Disease can also occur. Lower Intelligence Quiescent is associated with diffuse brain involvement.The most common neurological manifestations of tuberous sclerosis include, mental retardation, which can be severe and incapacitating, and seizures. 
In about 50-80% of tuberous sclerosis patient, kidneys are affected by bilateral AMLs (as in our case). AML may cause significant morbidity and mortality.  Normally, present kidney tissue becomes abnormal in quantity, arrangement and in degree of maturation and results in hamartoma formation. Histopathologically, hamartoma consists of fatty tissue with rich vascular tissue with many tortuous vessels, and smooth muscles.  Most (60%) of renal lesions of TSC are asymptomatic and are commonly found incidentally during routine imaging.  In a case series that included patients with isolated renal AML and patients with TSC, 82% of patients with tumor >4 cm were symptomatic, whereas, only 23% of patients with tumor <4 cm were symptomatic. These can become symptomatic because of renal enlargement and related complications. Usual symptoms triad (Lenk's triad) consists of flank pain (53%), a palpable tender mass (47%), and gross hematuria (23%). 
The reported complications of renal hamartomas include infection and or nephrolithiasis due to partial obstruction of collecting system and spontaneous hemorrhage. In 20% cases, hemorrhage is severe enough to result in shock. , Usually, 53% patient presented with lumbar pain and 23% present with gross hematuria (our patient presented with both).
The tumor is usually benign but renal cell carcinoma can also develop. ,, The ability to differentiate between AMLs and renal cell carcinomas is very important for treatment and prognosis. Ultrasonography can diagnose renal AMLs. Computerized tomography can differentiate between AML and renal cell carcinoma in 95% of cases. For histopathological confirmation, biopsy should be avoided as it can result in injury and bleeding thus, can lead to deterioration of renal function, sometimes necessitating nephrectomy. 
Only symptomatic patients with tumor bigger than 4 cm require treatment. Embolization and partial nephrectomy are available treatment modalities. Rarely nephrectomy carried out, if there is alarming hematuria.
| Conclusion|| |
In children with TSC, an early and periodic renal ultrasonography evaluation should be carried out as a part of renal surveillance to identify those patients in whom lesion is growing and can be treated with embolization or partial nephrectomy before a life threatening episode of spontaneous hemorrhage, which may necessitate nephrectomy. Renal ultrasonography must be carried out every 2-3 years before puberty and every year thereafter.
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[Figure 1], [Figure 2], [Figure 3]