Niemann-Pick is a rare genetic disease of severe progressive psychomotor retardation. In its acute form it is characterized by seizures and dementia. In 1978, in the American Journal of Human Genetics, Drs. E.J.T. Winsor and J.P. Welch of Halifax reported fifteen patients with the Nova Scotia variant (type D) of Niemann-Pick Disease (NS-NPD), adding three patients previously described twenty years earlier by Drs. A.C. Crocker and S. Farber. Because of the association of NS-NPD with a specific ethnic population in western Nova Scotia, we wich to describe its genetic and genealogical background which are of considerable interest and sometimes of crucial importance.

Evidence to date indicates that NPD is an autosomal recessive disorder in all of its forms. A recessive gene is present on one of the twenty-two pairs of autosomes or non-sex chromosomes and becomes manifest only if that gene is present in both parents. The disease may occur in one or more family members, and has increased frequency in certain populations from the same geographical area and/or similar ethnic background. Although usually manifest in children, NPD may first appear in adulthood. It is included in the group of diseases referred to as lipid storage diseases. It is characterized by an enlarged spleen, liver and lymph nodes, chronic diarrhea and malabsorption of food, and may exhibit mental retardation. Diagnosis is established by bone marrow and tissue biopsy, and few patients survive beyond early adulthood.

With the help of Father Clarence d'Entremont, Drs. Winsor and Welch found that the type D version of NPD could be attributed to three seventeen-century Acadian couples, common ancestors to all fifteen children, but also that most cases could be traced to one particular couple. It was established further that the parents of the fifteen patients were neither first nor second cousins, but must have been carriers of the same gene which caused NS-NPD. All fifteen patients who were studied lived within a radius of ten miles in Yarmouth County, and were in a specific school district. There were seven males and eight females.

Five sons of the first couple mentioned above returned after the Deportation of the Acadians and settled in one specific geographical area. Four of the sons constituted the second generation, the children of the fifth son all died before reaching adulthood. The descendants of the four sons attended school in the same district, yet families with affected children who did not live in this school district were also Acadians.

The frequency of affected children in the community was approximately 1%, while carriers were calculated to range between 10% and 26%. An indication on inbreeding in the community was provided with the help of genealogical investigation conducted on random chosen families having children in the school district. Ten children were chosen from the school registers. The genealogy of twelve of the twenty parents of the ten randomly chosen children was traced through both parents leading back, in every case, to at least one of the three main ancestral couples.

Because of the heightened awareness of family members to the disease, both desirable and undesirable consequences arose. Misunderstanding as to the nature and causes of NS-NPD led to some unnecessary anxiety. Young couples contemplating marriage were encouraged to have "blood tests", such as VDRL, in the mistaken belief that carriers could be identified. Anxious parents insisted on children being examined for the disease. On the positive side, clergy and other authority figures in the community encouraged marriage outside of the limited genetic group, while at the same time on-going community educational programs were recommended.

NS-NPD is confined to this small ethnic community in western Nova Scotia. Inbreeding may be a factor, but ther are similar Acadian communities elsewhere in Nova Scotia without any manifestation of NS-NPD. It is proposed that by chance several of the "founding fathers" must have carried the same abherrant gene leading to a high initial frequency of the disease. It is also speculated that the gene responsible for NS-NPD may have been a single new mutant.

This genetic research concerning the Nova Scotia variety of Niemann-Pick not only illustrates the potential for close community association between genealogy and genetics, but also demonstrates how crucial genealogy can be in intrpretation of the development of such rare familial diseases.

Bibliography:

• Crocker, A.C. and S. Farber, N.P. Disease, a Review of 18 Patients, in Medicine, 37 (1958), pp 1-93.

• The New Encyclopedia Brittanica, Macropedia, 15th ed., 1974, vol 5, p 858.
• d'Entremont, Clarence, Father, Les enfants de Philippe II Mius-d'Entremont, dit d'Azy in l'Histoire du Cap-Sable de l'an mil au traite de Paris (1763), vol III, Louisiana: Hebert, 1981, pp 968-1035.
• Frederickson, D.S. and H.R. Sloan, Sphingomelin Lipidosis: Niemann Pick Disease, in The Metabolic Basis of Inherited Disease, 3rd ed., 1972, pp 783-807.
• Ibbles, J.A. and J.P. Welch, Clinical and Genetic Data on twelve new cases of type D Niemann Pick Disease, (abst), in Pediatric Research, 6 (1972), p 364.
• Winsor, E.J.T. and J.P. Welch, Genetic and Demographic Aspects of NS Niemann Pick Disease (type D) in The American Journal of Human Genetics, 30 (1978), pp 530-538.