Table 1.
Clinical and Laboratory Findings in the CDAR-Enrolled Probands with VPS4A Mutations
| VPS4A (NM_013245.2) Mutations | Age, Sex, & Ethnic Background |
Laboratory Findings |
Age at First Transfusion | Transfusion Requirement | Non-hematologic findings | ||||
|---|---|---|---|---|---|---|---|---|---|
| Lowest Hb | ARC | MCV | Ferritin (F) / LIC | ||||||
| 1 | de novo c.850A>T (p.Arg284Trp) heterozygous | 6 y.o., F, European- and Hispanic-American | 7.3 (increased irritability when anemia worsens) | 380–500 | 89–98 | F 840, LIC 12.1 at 4y.o., now controlled with deferasirox | neonate (EGA 35 wks) | every 4–6 weeks | severe global developmental delay, microcephaly, microgyria, dystonia (axial hypotonia with appendicular hypertonia), suspected Leber congenital amaurosis and/or cortical blindness, failure to thrive, frequent urinary tract infections |
| 2 | de novo c.608G>A (p.Gly203Glu) heterozygous | 5 y.o., M, European- and Hispanic-American | 6.1 | 40–500 | 80–100 | F 4093, LIC 8.82 at 5y.o., on deferasirox | neonate (EGA 34 wks) | every 4–10 weeks | severe global developmental delay, seizure disorder, microcephaly, microgyria, dystonia (axial hypotonia with appendicular hypertonia), congenital bilateral cataracts, failure to thrive, chronic kidney disease (stage II-III) |
| 3 | c.83C>T (p.Ala28Val) homozygous | 3 y.o., F, Arabic | 6.9 | 240–400 | 88–99 | F 470 LIC 6.5, at 2.5 y.o. before starting deferasirox | neonate (EGA 35 wks) exchange transfusion for hyperbilirubinemia | occasionally (every 2–6 months) | global developmental delay, macrocephaly, dystonia (axial hypotonia with appendicular hypertonia), delayed myelination, esotropia, frequent urinary tract infections |
Abbreviations, normal range, and units: y.o., years old; Hb, hemoglobin concentration (11.5–13.5 g/dL); ARC, absolute reticulocyte count (29–80 106/μL); MCV, mean corpuscular volume (75–87 fL); F, serum ferritin (10–150 ng/mL); LIC, liver iron content (<2.4 mg/g dry liver weight) based on T2∗ MRI or Ferriscan; EGA, estimated gestation age. All the probands were noted at birth to have hepatomegaly and cholestasis that gradually improved. They have persistent splenomegaly.