Saving a Little Girl‘s Life

An exact diagnosis is the basis for an optimal treatment. Here is a case from our daily work where exome diagnostics saved a little girl’s life. 

Our patient had shown signs of severe illness at an early age. Her parents sought medical assistance when she was about six months old. Examining the baby, the physicians identified a bone marrow developmental defect. But the reasons for the deficiency remained unclear. However, the physicians knew that time was precious, since the little girl‘s older brother already died at the age of seven months, displaying similar symptoms. Facing this, the only option the physicians had was to prepare for bone marrow transplantation. The surgery posed a high risk for the girl‘s life because survival rates for this type of procedure for a baby are far from good, at around 50%. But the physicians also knew that if two siblings show such similar symptoms, there had to be a genetic cause.

Finding the needle in the haystack

To get results as fast as possible and to retain a chance to spare the girl the risky bone marrow transplantation, the treating physician approached CeGaT directly. CeGaT’s task was to analyze the DNA of the girl and both parents. At CeGaT, the DNA from the little girl and both parents was analyzed (so-called “trio exome diagnostics”).

Every human has thousands of genetic alterations and nearly all of them do not cause diseases. Finding the one genetic variant that causes a patient‘s disease is the wellknown “needle in a haystack problem”. This procedure requires a profound understanding of sequencing technology, molecular biology, and human genetics.

Gene analysis reveals a hidden condition

CeGaT was able to identify two variants in our patient, one inherited from each parent, in a gene called TCN2. The protein defined by this gene helps Vitamin B12 enter body cells, such as bone marrow cells. This is essential for bone marrow development. As the girl‘s blood values for vitamin B12 were normal, the physicians had no indication of this condition. In order to compensate for the reduced transfer of vitamin B12 into the bone marrow, the physicians decided to provide her with B12 supplements through medication and postponed the bone marrow transplantation. The treatment worked – the little girl recovered, bone marrow transplantation was not needed. She is developing well:
Today, she is a healthy, happy four-year-old girl.

For the many diseases that are inherited, genetic diagnostics give precise insights into their causes and pathomechanisms. Without genetic testing, the diagnosis very often remains vague and cannot be confirmed. Understanding a disease is the first step in choosing the best therapeutic option and thereby helping patients to get healthy or increase their quality of life drastically. Genetic diagnostics is a cost-efficient diagnostic tool that should be integrated early into the diagnostic plan of many patients – because an exact diagnosis is the basis for optimal treatment.

Case Overview

6 months old girl

Congenital bone marrow failure, recurrent infections, anemia, dystrophy, reduced neutrophil and thrombocyte count

Familial history:
Brother with same symptoms passed away at the age of seven months

Inital planned therapy strategy:
Bone marow transplantation. Chance of survival only approx. 50%

Genetic testing:
Trio exome diagnostics at CeGaT

Homozygous mutation in TCN2 (encodes for vitamin B12 carrier) leading to a defect in vitamin B12 metabolism (despite normal blood values)

No need for bone marrow transplantation. High-dose therapy with vitamin B12. Child can live a normal life

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