Humangenetik 26, 79--85 (1975) © by Springer-Verlag 1975
Nephrogenie Diabetes Insipidus in an Australian Aboriginal Kindred P. Schultz and D. R. Lines Department of Paediatrics, University of Adelaide, Adelaide Children's Hospital, North Adelaide 5006, South Australia Received June 24, 1974
Summary. Four Australian aboriginal children were found to have nephrogenic diabetes insipidus. They are the sons of 3 sisters who were shown to have a urinary concentrating defect uncorrected by vasopressin. An extensive genealogy did not reveal any caucasian genetic influence suggesting that a new gene~ic mutation was responsible. Nephrogenic diabetes insipidus is an inherited condition in which the renal tubules are unresponsive to vasopressin (Williams and Henry, 1947). I t is transmitted as a sex-linked incomplete dominant gene (Williams and Henry, 1947; Schoen, 1960) this being usually found in descendants of the original settlers of Nova Scotia, and has been traced to an immigrant ship, the Hopewell (Bode and Crawford, 1969). I t has also been described in a negro kindred from North America by Feigin, Rimoin and Kaufmann (1970) who pointed out that racial admixture could not be excluded. This paper describes an Australian aboriginal kindred in which an extensive genealogy strongly suggests no caucasian responsibility.
Patients
Case 1. The propositus was a a/12 month aboriginal boy who was admitted to the Alice Springs Hospital in the centre of Australia, from the aboriginal mission of Santa Teresa, from where all the cases described hereunder also came. His diagnosis at that time was malnutrition and dehydration. His weight on admission was 4.2 kg. He required repeated intravenous infusion for dehydration in association with diarrhoea. At the age of 5 months he was transferred to the Adelaide Children's Hospital and on arrival was considered to be dehydrated and malnourished. His serum sodium was elevated at 173 meq/1 and a pathogenic E. coli was cultured from his faeces. He was slowly rehydrated with saline and dextrose solutions and was able to be maintained on oral glucose-saline mixtures. However, his urinary output remained high (approximately 2 1/day) and minor respiratory infections caused dehydration requiring insertion of intravenous drips. These episodes of dehydration enabled measurement of urine osmolalities which were also estimated after 12 hrs of fluid deprivation. In all, 20 estimations of urinary osmolality were
80
P. Schultz and D. R. Lines
conducted and the values lay between 70 and 205 mosm/kg H20. I n addition, he had multiple injections of vasopressin-in-oil, the highest dose being 10 units following which the maximal urine osmolality was 140 mosm/kg H20 compared with a serum osmolality of 350 mosm/kg H20 at the same time. Two intravenous pyelograms were normal, except for poor concentrations of dye, and multiple microurines and colony counts revealed no formed elements or bacteruria. His serum creatinine and blood urea nitrogen values were normal when he was clinically hydrated but his serum sodium was always mildly elevated. Other tests of renal tubular function conducted and found to be normal were : urinary phosphate reabsorption (97%), reducing substances in urine (repeatedly negative), urinary amino acids (normal by paper and column chromatography), urinary mucopolysaccharides (not detected), and urinary p H of 4.9 when acidotic from dehydration. Thus the inability to concentrate appeared to be an isolated deficiency. When the diagnosis of nephrogenic diabetes insipidus was established he was started on chlorthiazide (as suggested by Crawford and Kennedy, 1959), 250 mg b.d. and a potassium supplement. This reduced his urinary output to approximutely 1 1/day and during 8 weeks of therapy his urine osmolality varied between 155 and 240 mosm/kg H20. During this period consequent upon his reduced fluid intake, his appetite improved and his weight increased from 2.93 to 5.56 kg. His serum Na averaged 150 meq/1. At this point a trial of therapy without chlorthiazide was instituted for 10 days. He only gained 0.09 kg, his serum Na averaged 160 meq/1 with a m a x i m u m value of 170 meq/1 and his fluid intake rose. Accurate 24-hour urine volumes were impossible because of perineal excoriation and diarrhoea. He was discharged to a convalescent hospital in Adelaide on ehlorthiazide but required 7 readmissions with respiratory infection or diarrhoea over the next 21 months. On one occasion, ut the age of 18 months, he developed a urinary tract infection which responded to cephsloridine. Repeat intravenous pyelogram and micturating cystourethrogram revealed no abnormality. Following recovery from this episode he was once again tested with vasopressin and urinary osmolality showed no response. He was eventually returned to Alice Springs at the age of 22 months on chlorthiazide. Case 2. A maternal cousin of case 1 (see Fig. 1) was admitted to the Alice Springs Hospital at age 11 months with malnutrition and chest infection. He remained in hospital with numerous episodes of dehydration in association with chest infection or diarrhoea until the age of 16 months. During this admission he required frequent intravenous infusions and parenteral alimentation. At 16 months he was transferred to the Adelaide Children's Hospital were he was found to be an irritable aboriginal child below the third percentile in all parameters (height 70 cm, weight 7.55 kg, and head circumference 45 era). Investigations were normal apart from a mildly elevated blood urea nitrogen on 2 occasions (22 and 23 rag%) and the isolation of Giardia lamblia from his faeces. While in hospital he had one episode of chest infection with exacerbation of diarrhoea and dehydration. He rapidly responded to intravenous therapy and
Nephrogenic Diabetes Insipidus in an Australian Aboriginal Kindred
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Nephrogenie Diabetes Insipidus in an Australian Aboriginal Kindred P. Schultz and D. R. Lines Department of Paediatrics, University of Adelaide, Adelaide Children's Hospital, North Adelaide 5006, South Australia Received June 24, 1974
Summary. Four Australian aboriginal children were found to have nephrogenic diabetes insipidus. They are the sons of 3 sisters who were shown to have a urinary concentrating defect uncorrected by vasopressin. An extensive genealogy did not reveal any caucasian genetic influence suggesting that a new gene~ic mutation was responsible. Nephrogenic diabetes insipidus is an inherited condition in which the renal tubules are unresponsive to vasopressin (Williams and Henry, 1947). I t is transmitted as a sex-linked incomplete dominant gene (Williams and Henry, 1947; Schoen, 1960) this being usually found in descendants of the original settlers of Nova Scotia, and has been traced to an immigrant ship, the Hopewell (Bode and Crawford, 1969). I t has also been described in a negro kindred from North America by Feigin, Rimoin and Kaufmann (1970) who pointed out that racial admixture could not be excluded. This paper describes an Australian aboriginal kindred in which an extensive genealogy strongly suggests no caucasian responsibility.
Patients
Case 1. The propositus was a a/12 month aboriginal boy who was admitted to the Alice Springs Hospital in the centre of Australia, from the aboriginal mission of Santa Teresa, from where all the cases described hereunder also came. His diagnosis at that time was malnutrition and dehydration. His weight on admission was 4.2 kg. He required repeated intravenous infusion for dehydration in association with diarrhoea. At the age of 5 months he was transferred to the Adelaide Children's Hospital and on arrival was considered to be dehydrated and malnourished. His serum sodium was elevated at 173 meq/1 and a pathogenic E. coli was cultured from his faeces. He was slowly rehydrated with saline and dextrose solutions and was able to be maintained on oral glucose-saline mixtures. However, his urinary output remained high (approximately 2 1/day) and minor respiratory infections caused dehydration requiring insertion of intravenous drips. These episodes of dehydration enabled measurement of urine osmolalities which were also estimated after 12 hrs of fluid deprivation. In all, 20 estimations of urinary osmolality were
80
P. Schultz and D. R. Lines
conducted and the values lay between 70 and 205 mosm/kg H20. I n addition, he had multiple injections of vasopressin-in-oil, the highest dose being 10 units following which the maximal urine osmolality was 140 mosm/kg H20 compared with a serum osmolality of 350 mosm/kg H20 at the same time. Two intravenous pyelograms were normal, except for poor concentrations of dye, and multiple microurines and colony counts revealed no formed elements or bacteruria. His serum creatinine and blood urea nitrogen values were normal when he was clinically hydrated but his serum sodium was always mildly elevated. Other tests of renal tubular function conducted and found to be normal were : urinary phosphate reabsorption (97%), reducing substances in urine (repeatedly negative), urinary amino acids (normal by paper and column chromatography), urinary mucopolysaccharides (not detected), and urinary p H of 4.9 when acidotic from dehydration. Thus the inability to concentrate appeared to be an isolated deficiency. When the diagnosis of nephrogenic diabetes insipidus was established he was started on chlorthiazide (as suggested by Crawford and Kennedy, 1959), 250 mg b.d. and a potassium supplement. This reduced his urinary output to approximutely 1 1/day and during 8 weeks of therapy his urine osmolality varied between 155 and 240 mosm/kg H20. During this period consequent upon his reduced fluid intake, his appetite improved and his weight increased from 2.93 to 5.56 kg. His serum Na averaged 150 meq/1. At this point a trial of therapy without chlorthiazide was instituted for 10 days. He only gained 0.09 kg, his serum Na averaged 160 meq/1 with a m a x i m u m value of 170 meq/1 and his fluid intake rose. Accurate 24-hour urine volumes were impossible because of perineal excoriation and diarrhoea. He was discharged to a convalescent hospital in Adelaide on ehlorthiazide but required 7 readmissions with respiratory infection or diarrhoea over the next 21 months. On one occasion, ut the age of 18 months, he developed a urinary tract infection which responded to cephsloridine. Repeat intravenous pyelogram and micturating cystourethrogram revealed no abnormality. Following recovery from this episode he was once again tested with vasopressin and urinary osmolality showed no response. He was eventually returned to Alice Springs at the age of 22 months on chlorthiazide. Case 2. A maternal cousin of case 1 (see Fig. 1) was admitted to the Alice Springs Hospital at age 11 months with malnutrition and chest infection. He remained in hospital with numerous episodes of dehydration in association with chest infection or diarrhoea until the age of 16 months. During this admission he required frequent intravenous infusions and parenteral alimentation. At 16 months he was transferred to the Adelaide Children's Hospital were he was found to be an irritable aboriginal child below the third percentile in all parameters (height 70 cm, weight 7.55 kg, and head circumference 45 era). Investigations were normal apart from a mildly elevated blood urea nitrogen on 2 occasions (22 and 23 rag%) and the isolation of Giardia lamblia from his faeces. While in hospital he had one episode of chest infection with exacerbation of diarrhoea and dehydration. He rapidly responded to intravenous therapy and
Nephrogenic Diabetes Insipidus in an Australian Aboriginal Kindred
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