Indian J Pediat 51: 255-257, 1984
Nephroflc syndrome in siblings
LS. Arvm, M.D., A. Jabar, M.D., M.A. QureshL M.D.R.G. Goel, M.D. and Meharban Singh, M.D.
Congenital nephrotic syndrome of Fin- nish type (I-3) which manifests during first three months of life and has a characteristic morphological changes in the kidney biopsy with an early fatal outcome is a rare but well recognised entity. It is an autosomal recessive disorder and familial occurrence is well documented. Till recently, late-onset familial nephrotic syndrome among siblings was considered as a rare entity. Familial nephrosis appears to be hetergeneous disor- der with possibly polygenic mode of inheri- tance. Clinical picture, laboratory features and outcome are similar to sporadic nephrosis. We report familial nephrotic syn- drome affecting two brothers.
A pair of siblings (two brothers) were brought to the Institute of Child Health, Kabul with a full blown picture of nephrotic syndrome. Parents were apparently normal and non consanguineous. Of their 3 sons, the youngest one (9-month old) was normal while other two developed nephrotic syn- drome. There was no history of similar ill- ness among siblings of close relatives.
Institute of Child Health, Kabul, Afghanistan and Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029.
Reprint requests: Dr. LS. Arya, Institute of Child Health, Kabul Afghanistan.
Case I: Mohammed Nazar, 9-yr old boy was hospitalised for generalised edema and oliguria of 5 days duration. He was first born with a full-term gestation. Pregnancy and delivery were normal. Family history of pulmonary tuberculosis was present. There was no history of recent diarrhea or history suggestive of malaria. Physical examination showed generalised edema. His blood pre- ssure was 110/70 mm Hg. There was no hepatosplenomegaly and kidneys were not palpable. Haemoglobin was 13 gm/dl, total leucocyte count 7600/mm 3 with polymorphs 70 percent, lymphocytes 24 percent, mon- ocytes 2 percent and eosinophils 4 percent. Sedimentation rate was 70 mm in first hour. Tuberculin test was negative. Urinalysis showed 4 plus proteinuria with hyaline casts. Urine was sterile on culture. His blood urea was 50 mg/dl, total serum proteins 2.4 gm/dl with albumin 1.6 gm/dl and globulin 0.8 gm/dl, serum cholesterol was 700 mg/dl. Skiagrams of chest and abdomen did not reveal any abnormality. He was put on pred- nisolone (2 mg/kg/day) and a high protein diet but developed a picture of fulminant septicemia with marked cellulitis of the abdominal wall and scrotum and died after 2 wk of hospitalisation. Case 2: Alamzar, 6-yr old boy, brother of Mohammad Nazar reported to the hospital with complaints of generalised edema of 9 months duration. There was no history of preceding sore throat or urinary complaints.
256 THE INDIAN JOURNAL OF PEDIATRICS Vol. 51, No. 409
History of pulmonary tuberclosis was pre- sent in the family. Physical examination showed generalised edema with mild pallor. His blood pressure was 110/70 mm Hg. There was no hepatosplenomegaly or enlargement of the kidneys. Hemoglobin of 11.4 gm/dl, total leucocyte count 10,000/ mm 3 with polymorphs 70, lymphocytes 23, monocytes 1 and eosinophils 6 percent. Erythrocyte sedimentation rate was 95 mm first hour Westergraen. Urine examination showed 4 plus proteinuria with hyaline casts. Tuberculin test was 15 mm positive. Skiagram of the chest showed fight hilar lymphadenopathy. Blood urea was 34 mg/ dl, total serum proteins 3.3 gm/dl with albumin 1.0 gm/dl and globulin 2.3 gm/dl. Serum cholesterol was 510 mg/dl. Urine cul- ture yielded growtlx of Esch. coli with a colony count of 40,000 per ml. The kidney biopsy, as seen under the light microscope apparently appeared normal. The glomeruli did not show any evidence of proliferative change or inflammatory exudate. However, in an occasional proximal convoluted tubule, hyaline droplets were observed in the lining of epithelial cells indicating an increased protein reabsorption.
The patient was put on prednisolone (2 mg/kg/day) along with antituberculous therapy but he left the hospital against medi- cal advice because of the death of his elder brother.
Apart from congenital nephrotic syn- drome of Finnish type which is a distinct entity and is clearly familial, the occurrence of late-onset nephrotic syndrome in siblings has rarely been reported. 4,5 Fanconi et al 6 in 1951 first described 6 families with 13 affec- ted siblings. Because of the paucity of reports
in the literature of familial nephrotic syn- drome it was generally believed that the incidence ofnephrotic syndrome in siblings or in consecutive generations of the same family is quite infrequent. However, an European survey conducted in 1969 on the basis of a questionnaire indicate that the incidence of familial nephrotic syndrome is not so rare. 7 Recently, Moncreiffet a/~ have studied the clinical, laboratory and renal morphological features as well as treatment and outcome of 15 pairs of siblings. Their findings suggest that the juvenile-onset familial nephrotic syndrome does not differ from non-familial forms of nephrotic syn- drome as far as the course of the illness and response to therapy is concerne& However, those patients with familial nephrotic syn- drome who develop the disease early during infancy have a relatively poor prognosis irrespective of the renal morphology.
Percutaneous kidney biopsy was per- formed in case-2 and was found to be essen- tially normal under light microscope. In minimal change nephrotics electron mic- roscopy is essential to identify fusion of the foot processes of the eipthelial calls along the basement membrane of glomeruli. However, with the aid of modern morpho- metric techniques it is possible to identify mild focal proliferative glomerular change even by light microscopy. 9 There is a good correlation between presence or absence of hematuria and hypertension with kidney morphology. The patients with structural glomerular changes invariably have hema- turia which is also ~i common findingin non familial nephrotics, l~ A high degree of con- cordance in clinical picture and renal morphology among affected siblings has been suggested 7"s but recently Kleinknecht et al II have reported an interesting famdy of 3- affected siblings in which there was a coexis-
ARYA ET AL : NEPHROTIC SYNDROME IN SIBLINGS 257
tence of congenital, infantile and juveni le nephrot ic syndrome.
The etiology of juveni le-onset famil ial nephrot ic syndrome is unknown. Unl ike the congenital nephrot ic syndrome of F inn ish type which is an autosomal recessive disor- der, the exact mode of inheritance in juveni le type familial nephrot ics is not clear. Nor io 12 has suggested a polygenic mode of inheritance because o f the association o f congenital heart disease and hypertrophic pyloric stenosis in some cases.
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