MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: nephrin (19q13.1)

Type 1 nephrotic syndrome
Congenital nephrosis
Finnish congenital nephrosis
CNF
NPHS1

Kidney failure
Anemia
Hypertension
Ascites
Mental changes
Uremia
Electrolyte imbalance

Congenital Nephrotic Syndrome, Finnish Type

Clinical Characteristics

General description (for patients):

Kidney failure can lead to severe and fatal health problems including anemia, hypertension, malnutrition, mental changes, and accumulation of fluid.  It can result from a variety of causes including infections, toxins, malformations and genetic mutations, often in adults.  At least two inherited types occur among plain people with advanced disease in infancy (see also polycystic kidney disease) or early childhood (Finnish type).  Treatment in the latter type can be effective if begun early, while renal dialysis and transplantation is available if needed later.

Medical description:  

Congenital nephrosis presents as a familiar picture of kidney failure with anemia, fluid accumulation, hypertension, uremia and electrolyte imbalances, etc.  Hypothyroidism , hypercholesterolemia, malnutrition and mental changes may be features as well.  In this disease, severe symptoms often appear before two years of age.  Because this type of congenital kidney disease is well known in Finland, an effective treatment protocol has been developed consisting of enalapril therapy, thyroid replacement, vitamin D and erythropoietin. Some small percentage of patients may have pyloric stenosis.

Genetics:

Congenital nephrotic syndrome type 1 is caused by a mutation in the nephrin gene on chromosome 19 (19q13.1).  It occurs with high incidence in the Old Order Mennonites in Eastern Pennsylvania in which a recessive homozygous deletion (1481delC) results in a frameshift and premature termination of the nephrin protein construction resulting in loss of function and the kidney disease.  Interestingly, one patient with this mutation has been found that is doubly heterozygous having this mutation plus a novel second one (3250delG), that may have been contributed via a non-Mennonite ancestor who joined this sect.

Treatment:

The Finnish protocol consisting of enalapril, vitamin D, erythropoietin and thyroid replacement can be effective early.

Prognosis:

The protocol treatment begun early may prevent the long term health effects of chronic kidney disease.

Ancillary treatments and support:

Renal dialysis and transplantation may be necessary in late stages of the disease.

Specialists and specialty centers:

Pediatrician, nephrologist, endocrinologist.

References:

Bolk, S., Puffenberger, E.G., Hudson, J., Morton, D.H., and Chakravarti, A.:  Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome, Finnish type, in the Old Order Mennonites. (Letter) Am. J. Hum. Genet. 65: 1785-1790, 1999. PubMed ID: 10577936


Worthen, H.G., Vernier, R.L., and Good, R.A.:  Infantile nephrosis: clinical, biochemical, and morphologic studies of the syndrome.  Am. J. Dis. Child. 98: 731-748, 1959. PubMed ID: 13845999


Sajantila, A., Salem, A.-H. Savolainen, P., Bauer, K., Gierig, C., and Paabo, S.:  Paternal and maternal DNA linkages reveal a bottleneck in the founding of the Finnish population.  Proc. Nat. Acad. Sci. 93: 12035-12039, 1996.  PubMed ID: 8876258


Resources: 


Nephrotic Syndrome
National Kidney Foundation

Associated Graphics