ABSTRACT:
Sickle cell haemoglobinopathy, a common haemolytic disease predominant in Western part of Orissa is a multisytemic disease, with varied manifestation. Through some case of nephropathy has been reported, earlier here we report a case of sickle cell disease (SED who had primary hypogonadism, hypertension and sickle cell Nephropathy. The pathogenesis and management are reviewed,.

KEY WORDS.
Sickle cell disease, primary hypogonadism, hypertension and sickle cell Nephropathy.

INTRODUCTION
Sickle cell haemoglobinopathy occurs due to genetic defect where due to mutation of  globin the 6th amino acid is changed from Glutamic acid to Valine. Due to dexoygenation there occurs structural changes in RBC Clinically the disorder manifests as chronic haemolysis repeated infection growth retardation and sickle cell crisis. The crisis includes alpastic crisis haemolytic crisis sequestration crisis and vasoocculsive crisis. Renal complications are encountered in some cases where the patient presents with haematuria proteinuria, renal insufficiency.

CASE REPORT
A 21 years male was admitted to this hospital in July 2005 with history of fever and jaundice for 5 days generalized pruritus for 4 days and decreased uriniation for 4 days. He had gradual diminished of vision of right eye since 5 years. He had taken Blod transfusion 2 months back at local hospital. On enquiry it was found that another brother who had sickle cell disease died 3 years back, due to vasoocculsive crisis. Both parents were found to be sickle cell trait. The patient had normal milestones of development but there was retarded development of secondary sexual characters and gyaecomastia since last 4 years (Fig.1.2)

On examination the patient had severe pallor and icterus, Blood pressure was 160/90 mmHg in both upper limbs. Pulse rate –110/min regular Temperature 100.20F respiration rate 18/minute. Per abdominal examination revealed moderate hepatomegaly and moderate spelenomegaly. He had bilateral gynaecomastia with sparse public and axillay hairs and facial hair. Both the testis volume were reduced (2.5 to 3 cm) soft with normal testicular sensations. Other systemic examinations including higher intellectual function were normal.

The laboratory examination showed:-
Hb:- 6.6% TLC- 8400/mm3, D/C –N 68 E 2L 30 M0 B 0
Serum Billrubin – Total 21 mg/dl
Direct 19 mg/dl.
S.G. O.T - 58IU/L
S.G. P.T - 57 IU/L
S. Alk Phospatase- 338IU/L
• Hb electrophosis showed SS band.
• Urine analysis showed – Albumin (++) with granular cast and RB Ci 30- 40/HPF and 24 hour urine protein was 300mg/in 24 hour with urine output- 2 Litres.
• Serum Zn- 7.5 (11.5-18..5 ml/L)
• Untrasonogram of abdomen showed moderate hepatomegaly, spelnomegaly (18cm) with coarse echotexture with spotty calcification. Both kidneys were normal size(11.0cm x 4.5cm) with diminished corticomeduallry differentiation.
• Chest x-ray and skull X- ray were normal.
• Foundscopy revealed papilloedema (Rt eye) with Grade II hypertensive retinopathy. Visual acuity was 6/60 in right eye and 6/9 in Left eye.
• Fasting lipid profile showed TC-109mg%, HDL-25mg% , LDL-50mg% , TG-376mg%, VLDL-75.30mg% , 212.86ngm/dL (270-1070mg/dl)
• Hormonal assay showed Testosterone –FSH – 8.41 IU/ml, LH17.97IU/Ml, Prolactin –5.45ngm/ml, TSH-3.79IU/ML, (0.5-4.7U/ml) 2.72U/ml) (1.6-23.0 ngm/ml).
• Kidney biopsy showed features of focal segmental glomerulosclerosis (Fig-3, Fig-4)

Patients was treated with antimalarial (Artesunate) antibiotic (Taxim) Pentoxyphylline, folic acid arginine Antihypertensive- Imandipril-10mg (ACE inhibitor) was started and responded well with normalization of BP. After 15 days of treatment the BP was controlled at 120/80 mm Hg, with reduction of Proteinuria. His serum bilirubin came down to 4.6mg/dl (total) and 3.8mg/dl (direct). The patient was discharged.

On subsequent follow up (after 45 days of discharge) 24 hours urine protein –25mg/24 hours, Urine output 2.5 Litres, BP was 120/70.

DISCUSSION:
The gonadal dysfunction as noted in sickle cell disease most often is attributed to primary gonadal failure. Levels of LH are usually increased in sickle cell disease. changes in FSH are usually inconsistent . Testosterone levels are almost always low in male adolescents and adults with sickle cell disease & these levels may respond poorly to GnRH stimulation.

Extreme delay in secondary sexual character is usually confined to males. Testicular size and volume are reduced and testicular histology showed immaturity of seminiferus tubules and replacement by hyaline materials secondary sexual character such as bearded growth, public and axilary hair are retarded.

The determinant of this type of growth may be chronic anemia patients with higher fetal hemoglobin have normal epiphyseal closures. Zinc level are lower in patient with sickle cell disease and studies have shown that zinc supplementation increased growth of body hair, increased testosterone levels and improved testosterone response to LHRH.

Sickle cell nephropathy in the form of glomerular disease occurs in 15 to 30% of sickle cell disease. Usually 15-30% patients develop proteinuria in the first 3 decades. The pathology is usually focal segmental glomerulosclerosis chronic renal failure can be predicted by presence of worsening anaemia, proteinuria, nephritic syndrome and hypertension. ACE inhibitors and ARB retard the progression of renal disease by lowering systemic & glomeruocapillary hypertension.

Hypoxia of renal medulla may also cause papillary necrosis. Coinheritance of microdeletion in  gene appear to protect against development of nephropathy. Cortical infarcts can cause persistent haematuria, pipiallry infects occurs in 50% of patients with sickle cell trait. Painless gross haematuria occurs with higher frequency in sickle cell trait than sickle cell disease.

Ultrasound examination may reversal a focal or diffuse increased echogenecity which is predominant in sickle cell disease. In the medulla renal tubules and vasarecta involvement can occur. Tubular changes results in atrophy dilatation, proteinacous cast and the so called thyroidization of renal medulla also occur.

In sickle cell disease the GFR is markedly elevated in young patients but decreases with age. As age increases the effective renal blood flow. effective plasma renal flow are decreased. Increased GFR, ERRF in sickle cell disease is usually due to increased synthesis of prostaglandins in early part which decrease in later life.

CONCLUSION
Sickle cell disease is a fairly common disease in this belt of India but usually the focus is directed towards managing vasoocclusive crisis.

But proteinuria, hypertension are the harbinger of sickle cell nephropathy and will respond to ACE inhibitors and ARB. The hypogonadism may be treated in early life by good nutrition, prevention of anaemia and zinc supplementation.