In Sum
Our patient is the third known patient with COG4-CDG (CDG-IIj) and represents a novel presentation of CDG due to COG4 defect with associated immune dysfunction manifesting as HLH and subsequent recurrent episodes of inflammation presenting with shock physiology.
CDG and inborn metabolism errors should be considered during diagnostic evaluation for patients with hemophagocytic lymphohistiocytosis symptoms, especially in very young patients who have previous evidence of developmental delays, neurologic symptoms (e.g., seizures and hypotonia), and liver dysfunction manifesting as coagulopathy, elevated serum transaminases and elevated serum ammonia.
CDG patients may also develop acute episodes of severe inflammation in the absence of cellular regulatory defects, for which FFP and protein C concentrate may have therapeutic value.
Jeffrey Lo, MD, is a third-year fellow in pediatric rheumatology at Boston Children’s Hospital.
Diagnostic Criteria for HLH
Hemophagocytic lymphohistiocytosis can be diagnosed if there is a mutation in a known causative gene or if at least five of eight diagnostic criteria are met:
- Fever (peak temperature of >38.5° C for >7 days)
- Splenomegaly (spleen palpable >3 cm below costal margin)
- Cytopenia involving >2 cell lines (hemoglobin <9 g/dL [90 g/L], absolute neutrophil count <100/mcL [0.10×109/L], platelets <100,000/mcL [100×109/L])
- Hypertriglyceridemia (fasting triglycerides >177 mg/dL
[2.0 mmol/L] or >3 standard deviations [SD] more than normal value for age) or hypofibrinogenemia (fibrinogen <150 mg/dL [1.5 g/L] or >3 SD less than normal value for age) - Hemophagocytosis (in biopsy samples of bone marrow, spleen or lymph nodes)
- Low or absent natural killer cell activity
- Serum ferritin >500 ng/mL (>1,123.5 pmol/Lng/mL)
- Elevated soluble interleukin 2 (CD25) levels (>2,400 U/mL or very high for age)
Source: Merck Manual, Professional Version
References
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