Benign familial haematuria in children from the Jewish communities of Israel: clinical and genetic studies.

Abstract

SUMMARY Over 7 years, 130 children were referred for prolonged isolated haematuria of unknown cause. In 34 instances, haematuria was also found in one or more family members. In 23 of these families (18 % of all referrals for isolated haematuria), investigation and follow-up, for periods of 5 to 10 years, of the index cases and of 56 haematuric relatives showed no evidence of renal disease and no other pathological findings. These subjects were diagnosed as having benign familial haematuria.The gene for benign familial haematuria is apparently transmitted as an autosomal dominant with reduced penetrance and variable expressivity. In Israel, the disorder seems to be more frequent among Jews of non-Ashkenazi descent than among those of European ancestry (Ashkenazim).Persistent or recurrent microscopical haematuria in otherwise healthy children represents a rather common clinical problem necessitating diagnostic procedures to identify or rule out renal disease, urinary tract pathology, or a haemorrhagic diathesis. Often, such examinations fail to reveal any cause for the haematuria. Many investigators (Baehr, 1926;Livaditis and Ericsson, 1962;Travis et al., 1962;Arneil et al., 1969;Johnston and Shuler, 1969;Glasgow et al., 1970) have concluded that the majority of such patients do not suffer from renal disease and have conferred upon them such diagnoses as 'idiopathic', 'benign', or 'essential' haematuria. In 1965, Ayoub and Vernier first reported a familial incidence of benign haematuria, a finding which has since been substantiated by others (McConville et al., 1966;Marks and Drummond, 1969;Rogers et al., 1973;Cotton et al., 1975). Since familial aggregation appeared to be a surprisingly common occurrence among children referred to our clinic because of persistent or recurrent haematuria, we decided to investigate all such cases seen over a 7-year period. Of these patients, 23 are believed to have benign familial haematuria (BFH). This paper describes the features on which the diagnosis was based and summarises clinical and genetic findings in this group of subjects.Received for publication 23 December 1978 Subjects and methods During the period 1966 to 1972, 130 children were seen in the Paediatric Nephrology Clinic of the Beilinson Medical Center with isolated, asymptomatic, persistent, or recurrent haematuria for which no cause could be found. This was defined as the finding of more than 10 erythrocytes per highpower field in 80 % or more of repeated urine examinations performed over a period of at least one year, and Addis counts showing more than 1 5 million erythrocytes per 12 h (our findings in healthy children are less than 0 5 million). In such cases urine analyses were performed on members of the immediate family (sibs and parents) and a family history was taken relating to renal disease, urinary findings, hypertension, deafness, and ocular anomalies. In 34 instances, haematuria was discovered in one or more members of the patient's family as a result of this search.The following investigations were ...

Evidence for Genetic Heterogeneity in Benign Familial Hematuria

“…Members with the first two subsequent negative urinalyses were treated as unaffected. Genetic analysis of these pedigrees showed that the most likely mode of transmission is autosomal-dominant with reduced penetrance (94%), in agreement with findings of other authors [15]. Linkage analysis with COL4A5 linked markers was performed in families 1 and 7 in which only females were affected, to check for X-linked Alport syndrome.…”

“…Single family lod score values were consistent with exclusion of linkage to COL4A3/COL4A4 in families 1 and 8 (table 2). Discussion BFH (MIM141200) is an autosomal dominant disease accounting for one-fifth of all hematuria of unknown cause in children [15]. Results from other authors suggest that BFH may be allelic to recessive Alport syndrome (AS: MIM 203780) with mutation in the COL4A3/COL4A4 locus [9].…”

Thin basement membrane nephropathy as a cause of recurrent haematuria in childhood

“…Although a family history is often evident, as in six of the eight children reported here, this is not invariable and, indeed, in some families with apparent benign familial haematuria the GBM appears to be normal (Waldherr 1982. Although in many instances the disorder is seen in more than one generation and appears to be transmitted as an autosomal dominant disorder (Rogers et al 1973, Eisenstein et al 1979. in other families siblings are affected whilst the parents appear to be normal, suggesting an autosomal recessive inheritance (Eisenstein et al 1979).…”

“…This figure is comparable to the frequency of Berger's IgA nephropathy, a conclusion also reached by Tiebosch et al (1989) in a study of Dutch adults with haematuria. Other authors (Cotton et al 1975, Eisenstein, Stark & Goodman 1979, Trachtman et al 1984) indicate that about 20% of children with asymptomatic isolated haematuria have TBMN.…”

Buffering Mechanisms in Aging: A systems approach towards uncovering the genetic component of aging

“…Our population, Ashkenazi Jews, is an ideal study group because social, political, and religious pressures limited this population to a relatively few founders [47]. This genetic homogeneity is paralleled by a relatively homogeneous socioeconomic and educational status.…”