Table 2.

Inherited Disorders with Normal ADA2 Enzyme Activity to Consider in the Differential Diagnosis of Adenosine Deaminase 2 Deficiency (DADA2)

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/DADA2Distinguishing from DADA2
Diamond-Blackfan anemia (DBA)12 ribosomal protein genes,
GATA1,
TSR2		ADPure red cell aplasiaMay have microcephaly, cleft palate & distinctive facies (hypertelorism, broad flat nasal bridge)
ADA-SCID 1 ADA ARImmune deficiency
  • Immune deficiency is much more severe.
  • Depletion of T, B, & NK cells
  • Low levels of ADA
  • Lack cerebrovascular disease & cutaneous manifestations
GATA2 deficiency (OMIM 614172) GATA2 ADImmune deficiency, cytopenia, recurrent infections 2
  • Infections are often invasive.
  • Vasculitic complications are rare.
Autoimmune lymphoproliferative syndrome (ALPS)CASP10,
FAS,
FASLG 3		AD
AR		Lymphadenopathy, splenomegaly, immune-mediated cytopenia 4ALPS, caused by primary defect in programmed cell death, has more autoimmune features.

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance

1.

ADA-SCID = severe combined immune deficiency caused by adenosine deaminase defects

2.
3.

Approximately 20%-25% of individuals with ALPS lack a genetic diagnosis (see ALPS).

4.

From: Adenosine Deaminase 2 Deficiency

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