Complete DiGeorge Syndrome (congenital athymia)

Daniel’s story

• Daniel was born 8 years ago after a perfect pregnancy, and he was considered a perfectly healthy baby boy at birth. Although he has had a few breathing difficulties, the doctor associated this to the hard birth labor he had been through.

• He had the BCG vaccine in his first day of life (tuberculosis vaccine is a live vaccine and it is part of the national vaccination schedule). Afterwards, we were discharged from the maternity ward.

• In the first 3-4 months we had a perfectly normal family life, we had guests, we went shopping, we went to the park and we had no idea that he was supposed to be kept in strict isolation. We were so happy as parents. Things just couldn’t have been better.”

“When Daniel was 4 months old, he suddenly got very ill. He had high fever, he developed a generalized rash, he had reflux and aspiration pneumonia, flu-like symptoms, difficulties in breathing and swallowing and he picked up rotavirus from the hospital waiting rooms.

He was immediately admitted to the hospital and things got from bad to worse.

• he started having low-calcium seizures due to very low PTH level (hypoparathyroidism);

• he didn’t respond to treatment;

• he developed severe infections leading to sepsis with multiple determinations: Klebsiella, Enterococcus, Staphylococcus and Fungus;

• he had otitis with 3 mastoidectomy surgeries, the last one leaving him with a permanent facial palsy on the left side;

The ear infections affected his hearing.

We have stayed in the hospitals for months without having answers for all of this.”

His health deteriorated rapidly, he lost 2 kg and he couldn’t eat anymore.

We were in shock because from a healthy baby, Daniel had become a severely ill child who was struggling to survive.

He was given no chance of survival.

We found an article about a doctor from Timisoara who specialized in primary immunodeficiencies. We took Daniel from the hospital in Bucharest and drove 700km to Timisoara to get some answers.

Dr Bataneant Mihaela in Timisoara immediately suspected his diagnosis: Complete DiGeorge Syndrome with total absence of T cells (congenital athymia). In Romania, doctors could only offer us bone marrow transplantation from unrelated donors, but this has a success rate of less than 30% for congenital athymia patients.

We had a huge decision to make! I felt so hopeless and this huge burden of making a life-or-death decision for my child was incredibly painful.

Determination that there is no thymus (athymia) is only based on blood tests* (never on X-Ray, CT scan or other scans):

• Usually < 50 T cells

Normal T cell number 2500 – 5500

• Always < 50 naïve T cells

Normal naïve number 1580-4900

*Thymic Transplantation, presentation July 2018 – Dr. M Louise Markert

Stem cells in the bone marrow make all the cells in the blood

Stem cells

B

T

Pre T

NK

BLOOD

PreT-cells “educated” in the thymus emerge into blood as naïve T-cells

THYMUS

Diagnosis of Complete DiGeorge Syndrome is based on athymia(see above).

Plus 1 of the following:

• Heart disease at birth

• Low calcium from small/ absent parathyroid glands

• 22q11 deletion syndrome

• CHARGE syndrome

Plus:

• absence of mutations in genes for severe combined immunodeficiency (SCID).

I started doing research on the internet and soon found Dr Louise Markert’s articles on Thymus transplantation. I have contacted Dr Markert and she has put me in touch with Dr Graham Davies from Great Ormond Street Hospital in London, UK.

The thymus transplantation procedure is only performed in two hospitals: Duke University, North Carolina, USA (Dr Louise Markert) and Great Ormond Street Hospital, London, UK (Dr Graham Davies).

Initially our Health Authority refused to pay for this procedure.

We had no other choice but to fundraise to save Daniel.

During this time, Daniel’s health deterioratedand he urgently needed a feeding tube. We were denied this in every hospital in Bucharest, as they considered him as being too risky for the surgery. Plus they didn’t believe that the surgery was necessary as he was already too ill to make it.

We took the little money we had fundraised and left for Austria to have the feeding tube and reflux surgery there. Things got complicated and we ended up being stuck there as Daniel’s health wasn’t good enough for him to fly back home. Eventually we returned.

Daniel got to have his life saving thymus transplantation when he was 1 year and 5 months old in Great Ormond Street Hospital in London with Dr Graham Davies, but complications did arise due to his late diagnosis and pre-transplant infections:

• Chronic cough and intermittent oxygen requirement;

• Chronic respiratory syncytial virus infection;

• Chronic BCG lymphadenopathy and needed 3 years of tuberculosis treatment;

• Chronic diarrhea with persistent rotavirus and clostridium difficile infection;

• Late immune system reconstitution (3 years after transplant);

• Autoimmune issues

• Facial palsy – mastoidectomy;

• Hearing loss.

Late diagnosis means: more infections, increased number of hospital admission days, more treatments and therapies, lower expected outcome and high mortality rate (vs. early diagnosis).

During Daniel’s diagnosis Odyssey he had:

• several sepsis episodes,

• 10 surgeries,

• 2 years of hospital admissions,

• BCG related infection, 3 years of strong TBC drugs, severe lymphadenopathy,

• 3 years of tube feeding,

• 3 mastoidectomy surgeries which caused a permanent facial palsy and hearing loss.

• 6 central lines inserted during 2 years of hospital admission (PICC lines, porth-a-cath, femoral line, jugular line).

All this could have been avoided with SCID newborn screening.

BCG related lymphadenitis

Late diagnosis also means so

much sufferingfrom the patient’s

perspective!

Today Daniel is a happy,smart, brave and kind littleboy. He loves trying newthings. He loves animals,outdoor trips, sports andplaying with other children,but the COVID-19 pandemicbrought us back to isolationin order to protect him.

He still has lower T cells than expected and he deals with issues related to DiGeorge syndrome like hypoparathyroidism, which can be hard to manage sometimes.