Clinical Problem
A 10 years old girl, second born of a non-consanguineous marriage was admitted (in Jaslok Hospital, Mumbai on 27/04/2002) with a history of increased frequency of urination and increased volume of urine since childhood and microscopic hematuria as seen on routine urine examination. She was passing large amounts of urine every 1-1½ hourly during day and used to wet her bed 2-3 times at night. This has been noticed particularly after she had an episode of malaria in 1999 (at 7 years of age), which was associated with gross hematuria. P. vivax and P. Falciparum were detected at that time and she received adequate treatment for the same. Fever subsided within 8-10 days, but repeat urine examinations continued to show microscopic hematuria.
There was no history of gross hematuria or burning micturition, fever, polydipsia. There was no past history of Koch’s or Koch’s contact. There was no puffiness of eyes, edema or symptoms suggestive of hypertension. There were no rash or joint pains, drug abuse or trauma. Family history did not reveal any hypertension, kidney disease or bleeding disorder. She was investigated 2 years ago at Surat. At that time her X-ray KUB, USG abdomen and voiding cystourethrogram was normal. She was treated with intranasal Desmopressin for nocturnal enuresis, but it was omitted after 3 months as it had no effect. Around the same time she complained of hearing difficulty and had been diagnosed as having bilateral sensorineural deafness by audiometry. She was fitted with hearing aid.
On physical examination she weighed 26.5 kg (11th centile) with a height of 134 cm (25th centile). Her vitals were stable. BP was 110/80 mm of Hg. She was pale. There was no edema (pedal or periorbital). Systemic examination was normal.
Investigations done prior to her admission on 27/04/02 were as follows:
Hb ranged from 10.5–12.2 gm/dl
WBC count ranged from 6500 – 10,600 cells/cumm (Polymorphs:67-75%, Lymphocytes : 27-30%, Eosinophils : 1-3%, Monocytes : 1-3%)
BUN ranged from 15-24 mg/dl and S. creatinine was between 0.5-0.8 mg%.
Serum C3, C4 were normal.
Urine: albumin +, RBCs- 80-100 /cumm (dysmorphic RBCs – 25%)
Tests for polyuria –
Serum Osmolality: 278-291 mosm/L.
Urinary Osmolality: 273-305 mosm/L
Urinary sodium: 36-40 meq/L
Urine specific gravity: 1005-1030
S. electrolytes, bicarbonate, calcium, phosphorus, uric acid: Normal
HIV, HBsAg, ASO titre, ANA – Negative.
USG KUB: Normal sized kidney
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Discussion
The diagnostic clues in this case were
(1) Persistent hematuria with mild proteinuria
(2) Sensorineural deafness
(3) Common causes of proteinuria + hematuria such as lupus nephritis, HBsAg associated glomerulonephritis were ruled out.
The next investigation advised was a kidney biopsy.
Kidney biopsy done on 24/05/02 showed:
Light microscopy: Focal moderate increase in mesangial cellularity
Electron microscopy – Changes of rarefaction, vacuolation and splitting consistent with Alport’s Syndrome.
Diagnosis: Alport’s syndrome
Unusual features: Alport’s syndrome is rare in female patients as the common mode of inheritance is sex linked recessive type. Alport’s syndrome is an inherited disorder of basement membrane of glomerular capillaries. There is a defect in the collagen synthesis of glomerular basement membrane e.g., COL A4, COL A5 etc. Many mutations are identified by DNA analysis with different modes of inheritance namely commonly sex linked recessive, autosomal recessive or dominant.
Alport’s syndrome progresses to end stage renal disease in males, but progresses slowly in female patients. This girl with Alport’s syndrome has normal renal function on follow up.
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