SUMMARY

 

1. Leukopenia has been reported in 3 diseases affecting branched-chain amino acid metabolism: 

- Methylmalonic acidemia (MMA)

- Propionic acidemia (PA)

- Isovaleric acidemia (IVA)

 

2. All three disorders present during infancy with vomiting, lethargy, failure to thrive, and metabolic acidosis. Developmental delay is typically present.

 

3. Immune abnormalities reported in MMA include neutropenia, pancytopenia, B and T cell lymphopenia, low IgG levels, and impaired phagocyte chemotaxis. Methylmalonic acid has been shown to inhibit bone marrow stem cell growth in vitro.

 

4. Immune abnormalities reported in PA include neutropenia, low IgG and IgM, and B cell lymphopenia.

 

5. Patients with IVA may develop neutropenia and pancytopenia during periods of acidosis, which may result in death from sepsis.

 

 

                                                                                                                            

OVERVIEW

 

 

          Leukopenia has been reported in 3 diseases affecting branched-chain amino acid metabolism: 

- Methylmalonic acidemia (MMA)

- Propionic acidemia (PA)

- Isovaleric acidemia (IVA)

 

          All three disorders present during infancy with vomiting, lethargy, failure to thrive, and metabolic acidosis. Developmental delay is typically present.

 

         Immune abnormalities reported in MMA include neutropenia, pancytopenia, B and T cell lymphopenia, low IgG levels, and impaired phagocyte chemotaxis. Methylmalonic acid has been shown to inhibit bone marrow stem cell growth in vitro.

 

         Immune abnormalities reported in PA include neutropenia, low IgG and IgM, and B cell lymphopenia. Patients with IVA may develop neutropenia and pancytopenia during periods of acidosis, which may result in death from sepsis.

 

 

                                           

EVALUATION

 

An immune evaluation should be performed for patients diagnosed with MMA, PA, or IVA.

 

 

Step 1: Immune Evaluation 

         

                      - CBC with Differential

- Lymphocyte subset enumeration by flow cytometry (CD3, CD4, CD8, CD19, CD16/56)

- IgG, IgM, IgA

- Specific antibody responses to vaccine antigens

 

                      - MMA neutropenia, pancytopenia, B and T cell lymphopenia, and low IgG levels have been reported.

- PA neutropenia, low IgG and IgM, and B cell lymphopenia have been reported.

- IVA neutropenia and pancytopenia have been reported.