On Hereditary Diabetes Insipidus With Special Regard to a Sex-Linked Form

Title: On Hereditary Diabetes Insipidus With Special Regard to a Sex-Linked Form
Author: Forssman, H.
Publisher: Acta Medica Scandinavica
Date Published: January 01, 1945
Reference Number: 287
This article is too long for us to reproduce here. The thesis was published as a book by Uppsala Universitet, Sweden, 1945.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

In this book, published in 1945, Forssman presents a study built upon five family lineages with a total of 83 known carriers of diabetes insipidus (DI) genes. His genealogical investigation covered around 5,500 subjects. Before reporting on his own methodologies and findings, Forssman reviewed the literature on diabetes insipidus. He recounts that it is a rare disease, affecting its bearers with polyuria (the chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst).

He describes how current clinical evidence pointed to the hypophysis as the site where the cause of DI could be found. Eventually, it was concluded that the antidiuretic hormone (ADH) was formed in the posterior lobe of the pituitary, whereas the diuretic principle was governed by the anterior lobe of the pituitary. ADH is essential if the kidney is to reabsorb body water. When the posterior lobe was damaged, it interfered with the circulation of ADH, preventing the kidney from reabsorbing body water. Some researchers thought DI could occur when the function of the anterior pituitary was enhanced to the point where it overpowered the pituitary lobe's antidiuretic function. Forssman notes that DI can either be acquired or inherited, that the early literature ascribes it occurring more in males than females, and that researchers could not reach a consensus on how to classify the different forms of DI.

The author reviews the history of diabetes insipidus in pregnancy, which concludes that polyuria is not a constant phenomenon at the end of pregnancy. And, when it does occur in women who do not have the inherited form of DI, it tends to occur later in pregnancy and clear up on its own after pregnancy.

Researchers at this time realized that DI could be inherited as well as acquired. The assumption was that the DI gene was inherited in a dominant pattern. A few researchers suggested that the hereditary pattern could be X-linked: the DI gene is carried by females who show mild to no symptoms of the disorder, and is passed by them to their sons, who show severe symptoms. Other researchers repudiated this idea.

The author's own work began with the examination of and studies on three family lineages, the largest of which extended over nine generations. In this lineage (AG), the DI-causing gene was without exception transferred by females, who showed mild to no symptoms, to their sons, who did. This supported the idea that at least one form of DI is inherited in an X-linked recessive manner. Two other lineages, H and J, (both much smaller than AG) also present the appearance of heredity through an X-linked gene. There were differences among the lineages. AG and H groups responded to administration of a pituitary extract by reduced urine, urine with a higher specific gravity and a higher chloride concentration. The DI patients from J group showed no such reaction. The author reasons that the difference in reactions derive from different mutations. Lineages K and L show an autosomal (non-sex) inheritance pattern.

Nine of the carriers for the X-linked form of DI and two of the carriers of the autosomal form showed plain or severe (but temporary) symptoms of DI in the latter half of their pregnancies.