Certainly not to minimize the many tragic losses people suffer every day, yet there can be little doubt that in earlier times untimely death was lurking ever closer, with minor illnesses posing greater threats. Hardly a family was untouched by the Grim Reaper and the loss of a child or more. So it was with Shadal, who lost several of his children. Originally, the apple of his eye was his eldest son, Ohev Ger, who many believed (the father included) was possessed with an even greater mind than his father. He died in 1853, aged 23, and with him Shadal's dream of a scholarly successor.
Of his other children's deaths, one which struck him particularly hard was the loss of his 18 year old daughter Miriam, who died the night after Shavuot, 1862. He had grown extremely close to Miriam, his oldest child by his second wife, and as we shall see, he studied with her, and of her own initiative she made herself very helpful to him. Always a man dealing with his own illnesses, he had become blind in one eye as a relatively young man. In his middle age he also lost most sight in his good eye, and of course this constrained him, since pretty much all he did was read and write. Miriam stepped up and from that point on she copied all his letters (his practice had been to actually write two copies of each letter, one to send and one to save). From time to time Shadal letters turn up on the market. If you have one from those later years, it may have been written by Miriam.
When she suddenly became sick and then died, he was heartbroken, as all parents are. He wrote movingly of this loss several times.
In the 1870s Shadal's son, the physician Isaia Luzzatto, began to publish many of his father's letters and writings. In 1878 he had an index of Shadal's letters printed, the Index raisonné des livres de correspondance de feu Samuel David Luzzatto, which not only lists all (or at least many) of Shadal's letters, broken down by date and language, but also includes short notes describing the content of many of them. The purpose of this index was to pave the way and whet the appetite of the public for the actual collected letters, which were eventually published in two separate collections; Igrot in Hebrew, and Epistolario, which gathered letters written in Italian, French and Latin. Isaia also included some specimens of letters at the end of the Index, as well as a couple of French poems, of a personal nature. One of them was written on the loss of Miriam and is dated the day after she died. Here is my translation:
6 June 1862
My Daughter is No More
After thirteen days of illness
At 2:30 this morning
She ceased living.
She was a force of brightness,
A superior mind.
Disregarding human weaknesses
Extremely rare for her sex.
Like that! my last hope vanished
I had hoped for a son, my pupil. (I had a lot of trouble with this line. Help?)
She studied with me all of the Torah,
Also half of Kohelet
And after learning that 'all is Vanity,'
At eighteen years
She left this world.
He wrote at least two more letters describing her virtues and his devastation at the loss. One was written in French, the same month, and is printed on the next page in the Index:
It describes how he continued to cope with the loss. Here is my translation:
". . . the world lost an angel of virtue, intelligence, diligence, modesty and beauty. A mind superior to its age and sex. She lived 18 happy years, then began to suffer, for her mind was above rank. Death delivered its inevitable sentence. Her father and mother remain forever inconsolable; this affliction will not fail to produce its positive effects. . . The wise man knows he is an instrument for the Most High, and he sees this.
"At first he is angered when events do not go his own way: לאויל יהרג כעש ('Anger kills the foolish man' Job 5.2). Then he adjust to the will of one wiser than his, and strives to task it imposes on him. It does not yield to blind necessity - it obeys the supreme wisdom. He is not a Stoic. He is not a bigot. He sees the final reasons, he loves the eternal wisdom, and is happy to go where it calls, ודי בזה, and this is enough.
"Sir, I received your two letters. Your words, your sympathy have relieved my pain . . ."
Finally, he wrote a Hebrew letter to Eliezer Lipmann Silbermann about one month after Miriam died. Here it is:
"God's hand touched me and took her from me these 30 days ago, the eve after Shavuot - the beloved of my soul, my only daughter Miriam, aged 18. None was like her with her combined qualities of intelligence, good character and beauty. This has further weakened and aged me, all the more as I see my wife in great sadness, inconsolable. My daughter had no other teacher but her mother, who read with her French, Italian, and German authors, and with all this, she was constantly involved in the housework, major and minor work, ironing and so forth. She even taught herself to write in Rashi script and to read and write Greek. She began to copy my letters, for her desire all her days was to help and assist, without any self-aggrandizement. Her face appeared like God's angel, delightful to all who saw her. Her wisdom and righteousness were apparent in her countenance, while she was modest and quiet. She was healthy and strong all her life, and in 13 days she took ill and died, and no one knows what her illness was. "
 His first daughter, Regina Malkah, was born in 1833 and died in 1851, also aged 18.