| Abstract|| |
A significant number of renal diseases in children occur as a result of genetic susceptibility. It is believed that such diseases, particularly those with an autosomal recessive transmission, may be more common in places with a high rate of consanguineous marriages as in the Middle East including the Kingdom of Saudi Arabia (KSA). Although a comparison of the published literature from the KSA with that from other countries outside the region support such a possibility, too few studies have been published from the region to definitely answer the question. Preliminary observations indicate that the children in the Kingdom probably have a higher incidence of polycystic kidney disease, familial juvenile nephronophthisis, congenital urological anomalies and familial nephrotic syndrome. It is reasonable to speculate that whereas some diseases may be common, others may be rare because of a low gene frequency in the local population.
|How to cite this article:|
Mattoo TK. Genetically Transmitted Renal Diseases in Children: A Saudi Perspective. Saudi J Kidney Dis Transpl 1998;9:105-9
|How to cite this URL:|
Mattoo TK. Genetically Transmitted Renal Diseases in Children: A Saudi Perspective. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2020 Feb 26];9:105-9. Available from: http://www.sjkdt.org/text.asp?1998/9/2/105/39280
| Introduction|| |
Genetically transmitted renal diseases constitute a significant portion of the renal problems in childhood. Some are hereditary and have a well-defined autosomal or X-linked inheritance such as in polycystic kidney disease and Alport's syndrome respectively. Other diseases are common amongst families including siblings and are believed to have a genetic predisposition. This occurs in certain types of congenital urological anomalies such as vesicoureteral reflux  .
In the Kingdom of Saudi Arabia (KSA) about two-thirds of the marriages occur between cousins. The incidence of genetically transmitted renal diseases, particularly those with an autosomal recessive pattern, is presumed to be high. The exact prevalence is not known because the literature on the subject is scanty. Almost all the studies published so far are from referral centers in Riyadh. Their interpretation is difficult because of inadequate demographic data and an undefined referral system. However, comparison with similar studies from referral centers in other parts of the world provides a partial perspective on the spectrum of some of the renal diseases in children in the Kingdom.
| Polycystic Kidney Disease and Familial Juvenile Nephronophthisis (FJN)|| |
Two well-known hereditary renal diseases, not uncommon in children, are polycystic kidney disease and familial juvenile nephronophthisis (FJN).
The polycystic kidney disease may be autosomal recessive (ARPKD) which is more common in children, or dominant (ADPKD), seen mostly in adults. The exact genetic defect in ARPKD is not known. In ADPKD, about 90% (PKDl) of the patients are known to have a defective gene linked to short arm of chromosome 16 (16p), about 5% (PKD2) have a defective gene on chromosome 4, and the remaining (PKD3) are believed to have a different gene defect which has not been identified  .
FJN was previously considered to be identical to the medullary cystic kidney (MCK), but the two are now known to be genetically different. FJN is an autosomal recessive disorder which usually presents in childhood whereas MCK has an autosomal dominant inheritance and is more common in adults. The clinical and the histological features of the two diseases are similar. A gene (NPH1) responsible for 90% of FJN patients maps to chromosome 2  . The exact incidence of polycystic kidney disease and FJN in the Kingdom of Saudi Arabia is unknown. Both seem to be common, particularly ARPKD. In a study of 100 children with chronic renal failure 6 (6%) had polycystic kidneys and 5 (5%) had FJN, the latter presenting mostly as Laurence-Moon-Biedl syndrome  . In another study  , 21 children with ARPKD were admitted to the Maternity and Children's Hospital, Riyadh (MCH) over a period of about 42 months; an apparently high incidence when compared to a reported incidence of about 1:6000 to 1:14,000 births  .
| Urological Abnormalities|| |
The incidence of congenital urological abnormalities in children in the KSA is believed to be high. This perception is based on studies which indirectly support such a possibility. Meta-analysis  of three studies from the KSA (4, 8, 9) revealed that 84 (31 %) of the 270 patients had CRF due to the malformations of the urinary tract. Included were reflux nephropathy in 45 patients and posterior urethral valve in 28 patients. This appears to be substantially higher than a reported incidence of 16% in France  .
Mahmoud et al  reported a higher incidence of congenital renal anomalies in children presenting with acute renal failure, 14% versus 2% in the UK  . According to one study, children investigated for urinary tract infection revealed radiological abnormalities in 64% of them  , which is higher than a reported incidence of about 50% from the UK  . However, in another study from KSA, Mugeiren et al  found that only 22 (46%) of their 40 children investigated for UT1 had radiological abnormalities.
| Nephrotic Syndrome|| |
Nephrotic syndrome (NS) is one of the commonest renal problems in childhood. It is mostly idiopathic in origin and such patients are known as having primary NS. During the first year of life it is called congenital (CNS) if the disease occurs during the first three months of life, or infantile when it occurs between 4-12 months of life.
The best known form of CNS is the Finnish type, which though common in Finland has been reported from other parts of the world, including Saudi Arabia. It is an autosomal recessive disease and the responsible gene had been mapped to the long arm of chromosome 19  .
No specific pattern of genetic transmission is seen in other children with primary NS. Nonetheless, variations in the overall prevalence of the disease in various countries, differences in histologic categories in different populations, a familial predisposition, particularly for MCNS and FSGS, and a possible association with certain MHC alleles  supports the possibility of the genetic susceptibility.
In a study in Saudi Arabia, 9 (6%) of the 150 children with primary nephrotic syndrome had a family history of the disease in another sibling, three times higher than the reported incidence of 2% in other countries  . The disease also seems to be more common in the first year of life. In a study involving 100 kidney biopsies, 13 (13%) were noted to be from children less than one year old  . Interpretation of this data in terms of the total number of children (210) seen with nephrotic syndrome revealed an overall incidence of 6.1%, three times the reported incidence elsewhere  .
In another study in 17 infants, 11 had congenital and six had infantile NS. Ten of the 17 patients had consanguineous parents. Two patients in this study had Finnish microcystic disease  . Of the various histological types of primary nephritic syndrome, children in the KSA show a relatively high frequency of diffuse mesangio-proliferative glomerulonepritis (MesPGN); it is not known whether the difference is genetic or environmental , .
| Renal Tubular Defects|| |
Renal tubular acidosis (RTA) is one of the commonest renal tubular defects in childhood. It may be proximal (type II), distal (type 1) or the hyperkalemic (type IV) type. Each may be sporadic or inherited, and isolated or secondary. Of the isolated inherited types, type II is usually inherited by an autosomal dominant trait where as the type I is inherited by dominant as well as recessive traits. Many of the secondary forms of RTA have a strong genetic predisposition. Type II RTA may be apart of the Fanconi syndrome, which occurs, in many autosomal recessive diseases such as cystinosis, galactosemia, Wilson disease, tyrosinemia and hereditary fructose intolerance. Similarly, type I RTA may also occur secondary to inherited diseases such as sickle cell nephropathy, medullary sponge kidney, Ehlers-Danlos syndrome More Details, and elliptosis etc  . In view of a strong genetic susceptibility, it is reasonable to expect a higher incidence of RTA in the Kingdom, however, to the best of my knowledge; no study has been published on the subject. Similar statements apply to many other well-defined heredity renal diseases such as Bartter's syndrome, Alport's syndrome, Nail-patella syndrome, Liddles syndrome (pseudohyperaldosteronism), cerebro-hepatorenal syndrome of Zellweger etc.
| Urolithiasis|| |
Renal calculi are uncommon in children and only 1% of all patients with renal calculi admitted to hospital are under the age of 16 years  . The incidence of urolithiasis in the Kingdom is believed to be high. About 5% of renal admissions at the MCH suffered from urolithiasis; a high incidence when compared to other countries  . This is attributed to a high protein diet with high oxalate to calcium ratio. Also, highpurine and acid ash content, augmented by a low urine output predispose to stone formation  . Genetic factors, however, have not been ruled out.
Primary hyperoxaluria (oxalosis) is a rare autosomal recessive disorder, which leads to nephrolithiasis. At MCH, six patients were diagnosed with oxalosis over a period of three years and included were two identical twin infants from consanguineous parents  . Interestingly, only one patient with cystinosis was seen over this period, an unpublished observation indicating that the disease may be uncommon in the KSA.
| Other Diseases|| |
Some rare renal diseases with a familial predisposition have been reported in children from the region.
Ohlsson et al  reported a syndrome of osteopetrosis, renal tubular acidosis and cerebral calcification. The disease, called as "marble brain disease", is associated with stunted growth and mental retardation and has been linked to carbonic anhydrase II enzyme deficiency  . Mattoo and Akhtar  reported a syndrome of familial glomerulopathy and proximal tubular dysfuction. It is possible that in view of a high rate of consanguinity some other rare renal disorders may exist in the KSA and the region.
In conclusion, the preliminary data on Saudi children indicates a relatively high incidence of certain genetically transmitted renal diseases. A multi-center study incorporating the demographic data is needed to confirm these observations. Recent advances in molecular biology have made it possible to make accurate diagnoses, detect genetic variations in apparently clinically homogenous diseases and identify the hitherto undescribed genetic basis of many other renal diseases. The patient population in the Kingdom of Saudi Arabia and the region provides a unique pool for such studies, an opportunity not to be missed.
| Acknowledgment|| |
I am grateful to Dr. Alan B. Gruskin, Chairman, Department of Pediatrics, for helpful suggestions on the manuscript.
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Tej K Mattoo
Associate Professor of Pediatrics, Wayne State University School of Medicine Staff Physician, Pediatric Nephrology, Children's Hospital of Michigan, 3901 Beaubien Boulevard, Detroit, MI 49201