The author reviews the literature of the familial incidence of Gaucher’s disease. Almost all the familial cases which have been described occurred in the members of one generation (siblings or cousins) only. To these cases reported in the literature the author adds 25, of which 4 were "sporadic" cases. The other 21 cases occurred in 6 families. The pedigrees of these families are presented. After an analysis of the available data the author presents the following hypothesis for the hereditary mechanism in these families:
Gaucher’s disease is a mutation which, once established, is transmitted as a simple dominant hereditary trait. In the affected individuals this trait gives rise to a disturbance of lipid metabolism which results in the accumulation of kerasin in the reticulum cells throughout the body. The severity of the disease may vary considerably. It can be present in such a slight degree that the amount of kerasin accumulated during life is too small to give rise to clinical manifestations. In other cases the progression may be so slow that the disease becomes manifest only in old age, provided the affected individual lives long enough. In these "subclinical cases," a diagnosis of Gaucher’s disease can sometimes be made by the detection of "early Gaucher cells" in the sternal marrow. Individuals thus affected suffer from Gaucher’s trait rather than from the actual disease. However, they can transmit the disease to 50 per cent of their offspring, and thus function as (almost) normal "carriers." In the family trees presented, it appeared that the disease tended to become more severe in every succeeding generation until after two or three generations it became clinically manifest in the affected individuals early in life. In the next generation it would then establish itself during fetal life so as to give rise to abortion, stillbirth or early death of the affected infant. In this way the mutation extinguishes itself, by permitting only the unaffected offspring of the affected individuals to persist. As a practical conclusion it is urged that a sternal marrow examination be included in every genetic investigation of Gaucher’s disease as the best method available at present for the detection of subclinical cases or "carriers."