Summary of genetic, clinical, and laboratory findings of the patient (ORAI1 p.H134P/L194P)
| Clinical features . | |
|---|---|
| Age at presentation | 4 mo |
| Age at death | 13 mo |
| Mutation | ORAI1 c.401A>C (p.H134P); c.581T>C (p.L194P) |
| Type of mutation | GOF/LOF (p.H134P); LOF (p.L194P) |
| Mode of inheritance | AR |
| Infections | Pneumococcal sepsis, CMV infection (viremia, retinitis, pneumonitis) |
| Muscular hypotonia | Yes |
| Anhidrosis | Probable |
| Enamel development defect | N/A |
| Hypotrichosis | Yes |
| Age at HSCT | 10 mo |
| Donor | 10/10 matched unrelated donor |
| Number of transplants | 3 |
| Graft used | Sorted CD34+ stem cells; donor CMV-specific cytotoxic T cells |
| Conditioning used | Treosulfan, fludarabine |
| HSCT complications | Graft failure, severe graft-vs-host disease, persistent CMV infection respiratory failure, severe neurological inflammation |
| Clinical features . | |
|---|---|
| Age at presentation | 4 mo |
| Age at death | 13 mo |
| Mutation | ORAI1 c.401A>C (p.H134P); c.581T>C (p.L194P) |
| Type of mutation | GOF/LOF (p.H134P); LOF (p.L194P) |
| Mode of inheritance | AR |
| Infections | Pneumococcal sepsis, CMV infection (viremia, retinitis, pneumonitis) |
| Muscular hypotonia | Yes |
| Anhidrosis | Probable |
| Enamel development defect | N/A |
| Hypotrichosis | Yes |
| Age at HSCT | 10 mo |
| Donor | 10/10 matched unrelated donor |
| Number of transplants | 3 |
| Graft used | Sorted CD34+ stem cells; donor CMV-specific cytotoxic T cells |
| Conditioning used | Treosulfan, fludarabine |
| HSCT complications | Graft failure, severe graft-vs-host disease, persistent CMV infection respiratory failure, severe neurological inflammation |
| . | Patient . | Reference range . |
|---|---|---|
| CBCa | ||
| White cell count (109/Liter) | 6.7 | 5.0–17.0 |
| Lymphocytes (109/Liter) | 4.0 | 2.0–13 |
| Monocytes (109/Liter) | 0.2 | 0.2–1.2 |
| Neutrophil (109/Liter) | 2.0 | 0.8–8 |
| Eosinophil (109/Liter) | 0.5 | 0-1.1 |
| Immunological resultsa | ||
| CD4 T cells (×109/Liter) | 2.44 | 1.5–5.0 |
| CD8 T cells (×109/Liter) | 0.40 | 0.50–1.60 |
| NK cells (×109/Liter) | 0.12 | 0.1–1.3 |
| B cells (×109/Liter) | 1.00 | 0.60–3.00 |
| IgM (g/Liter) | 2.06 | 0.24–0.95 |
| IgG (g/Liter) | 19 | 1.68–5.76 |
| IgA (g/Liter) | 3.7 | 0.05–0.74 |
| NK cell function (51Cr release assay and degranulation [CD107a expression]) | Significantly reduced compared with HD | N/A |
| Proliferation to PHA stimulation in vitro | Significantly reduced compared with HD | N/A |
| Immune dysregulation | HLHb: | |
| Fever | | |
| Hepatosplenomegaly | | |
| Anemia (Hb 74 g/l) | 95-140 | |
| Thrombocytopenia (73 × 109/Liter) | 150-600 | |
| Hypofibrinogenemia (0.6 g/Liter) | 1.5–6 | |
| Hyperferritinemia (1,293 µg/Liter) | 30-300 | |
| Hypertriglyceridemia (3.2 mmol/Liter) | 0.5–1.4 | |
| High LDH (2116 U/Liter) | 313-618 | |
| . | Patient . | Reference range . |
|---|---|---|
| CBCa | ||
| White cell count (109/Liter) | 6.7 | 5.0–17.0 |
| Lymphocytes (109/Liter) | 4.0 | 2.0–13 |
| Monocytes (109/Liter) | 0.2 | 0.2–1.2 |
| Neutrophil (109/Liter) | 2.0 | 0.8–8 |
| Eosinophil (109/Liter) | 0.5 | 0-1.1 |
| Immunological resultsa | ||
| CD4 T cells (×109/Liter) | 2.44 | 1.5–5.0 |
| CD8 T cells (×109/Liter) | 0.40 | 0.50–1.60 |
| NK cells (×109/Liter) | 0.12 | 0.1–1.3 |
| B cells (×109/Liter) | 1.00 | 0.60–3.00 |
| IgM (g/Liter) | 2.06 | 0.24–0.95 |
| IgG (g/Liter) | 19 | 1.68–5.76 |
| IgA (g/Liter) | 3.7 | 0.05–0.74 |
| NK cell function (51Cr release assay and degranulation [CD107a expression]) | Significantly reduced compared with HD | N/A |
| Proliferation to PHA stimulation in vitro | Significantly reduced compared with HD | N/A |
| Immune dysregulation | HLHb: | |
| Fever | | |
| Hepatosplenomegaly | | |
| Anemia (Hb 74 g/l) | 95-140 | |
| Thrombocytopenia (73 × 109/Liter) | 150-600 | |
| Hypofibrinogenemia (0.6 g/Liter) | 1.5–6 | |
| Hyperferritinemia (1,293 µg/Liter) | 30-300 | |
| Hypertriglyceridemia (3.2 mmol/Liter) | 0.5–1.4 | |
| High LDH (2116 U/Liter) | 313-618 | |
Abbreviations: AR, autosomal recessive; PBMC, peripheral blood mononuclear cell; CMV, cytomegalovirus; Ig, immunoglobulin; HSCT, hematopoietic stem cell transplantation; GvHD, graft-versus-host disease; HD, healthy donor; PHA, phytohemagglutinin. The reference range is adjusted for age. Bold values are outside the reference range.
Age of analysis: 5 mo.
Age at analysis: 4 mo.