Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro

Linda Stork, Daniel R. Ambruso, Stephen F. Wallner, James E. Sambrano, Lynn C. Moscinski, Harry L. Wilson, Edward R B McCabe

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

This study investigated the hematologic abnormalities of an infant with propionic acidemia and reversible pancytopenia. Light and electron microscopy of her bone marrow revealed severely disturbed cellular morphology with trilineage dysmyelopoiesis, hemophagocyto-sis, and numerous multinucleated histiocytes and megakaryocytes. The effects of her serum and of organic acids associated with propionic acidemia were studied on hematopoiesis in vitro. Mouse erythroid (CFU-E) and granulocyte-monocyte colonies (CFU-GM) were assayed by fibrin clot technique; human CFU-GM were grown in agar culture. The infant's serum reduced mouse CFU-E and CFU-GM by 43 and 32%, respectively, compared with normal human sera, but had no effect on human CFU-GM in our culture system. Buffered propionic acid caused concentration-dependent inhibition of mouse CFU-E and human CFU-GM over a range reported in sera of acutely ill infants with propionic acidemia. Neither cell viability nor subsequent colony formation was diminished by preincubation of bone marrow cells with propionic acid for 48 h. The three other organic acids studied, tiglic acid, 3-OH propionate, and glycine, did not inhibit growth of mouse CFU-E, CFU-GM, or human CFU-GM, and glycine significantly enhanced formation of the latter. Evaluation of the infant's hematologic abnormalities suggests that inhibition of bone marrow proliferation and maturation and, perhaps, shortened red blood cell survival were responsible for her pancytopenia. The studies performed in vitro implicate propionic acid in this hematopoietic dysfunction.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalPediatric Research
Volume20
Issue number8
StatePublished - 1986
Externally publishedYes

Fingerprint

Propionic Acidemia
Erythroid Precursor Cells
Pancytopenia
Hematopoiesis
Granulocytes
Monocytes
Serum
Glycine
Cell Survival
Bone Marrow
In Vitro Techniques
Acids
Histiocytes
Megakaryocytes
Propionates
Fibrin
Bone Marrow Cells
Agar
Electron Microscopy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Stork, L., Ambruso, D. R., Wallner, S. F., Sambrano, J. E., Moscinski, L. C., Wilson, H. L., & McCabe, E. R. B. (1986). Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro. Pediatric Research, 20(8), 783-788.

Pancytopenia in propionic acidemia : Hematologic evaluation and studies of hematopoiesis in vitro. / Stork, Linda; Ambruso, Daniel R.; Wallner, Stephen F.; Sambrano, James E.; Moscinski, Lynn C.; Wilson, Harry L.; McCabe, Edward R B.

In: Pediatric Research, Vol. 20, No. 8, 1986, p. 783-788.

Research output: Contribution to journalArticle

Stork, L, Ambruso, DR, Wallner, SF, Sambrano, JE, Moscinski, LC, Wilson, HL & McCabe, ERB 1986, 'Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro', Pediatric Research, vol. 20, no. 8, pp. 783-788.
Stork L, Ambruso DR, Wallner SF, Sambrano JE, Moscinski LC, Wilson HL et al. Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro. Pediatric Research. 1986;20(8):783-788.
Stork, Linda ; Ambruso, Daniel R. ; Wallner, Stephen F. ; Sambrano, James E. ; Moscinski, Lynn C. ; Wilson, Harry L. ; McCabe, Edward R B. / Pancytopenia in propionic acidemia : Hematologic evaluation and studies of hematopoiesis in vitro. In: Pediatric Research. 1986 ; Vol. 20, No. 8. pp. 783-788.
@article{094e16dca4444f85b4536389b8f0f0e7,
title = "Pancytopenia in propionic acidemia: Hematologic evaluation and studies of hematopoiesis in vitro",
abstract = "This study investigated the hematologic abnormalities of an infant with propionic acidemia and reversible pancytopenia. Light and electron microscopy of her bone marrow revealed severely disturbed cellular morphology with trilineage dysmyelopoiesis, hemophagocyto-sis, and numerous multinucleated histiocytes and megakaryocytes. The effects of her serum and of organic acids associated with propionic acidemia were studied on hematopoiesis in vitro. Mouse erythroid (CFU-E) and granulocyte-monocyte colonies (CFU-GM) were assayed by fibrin clot technique; human CFU-GM were grown in agar culture. The infant's serum reduced mouse CFU-E and CFU-GM by 43 and 32{\%}, respectively, compared with normal human sera, but had no effect on human CFU-GM in our culture system. Buffered propionic acid caused concentration-dependent inhibition of mouse CFU-E and human CFU-GM over a range reported in sera of acutely ill infants with propionic acidemia. Neither cell viability nor subsequent colony formation was diminished by preincubation of bone marrow cells with propionic acid for 48 h. The three other organic acids studied, tiglic acid, 3-OH propionate, and glycine, did not inhibit growth of mouse CFU-E, CFU-GM, or human CFU-GM, and glycine significantly enhanced formation of the latter. Evaluation of the infant's hematologic abnormalities suggests that inhibition of bone marrow proliferation and maturation and, perhaps, shortened red blood cell survival were responsible for her pancytopenia. The studies performed in vitro implicate propionic acid in this hematopoietic dysfunction.",
author = "Linda Stork and Ambruso, {Daniel R.} and Wallner, {Stephen F.} and Sambrano, {James E.} and Moscinski, {Lynn C.} and Wilson, {Harry L.} and McCabe, {Edward R B}",
year = "1986",
language = "English (US)",
volume = "20",
pages = "783--788",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Pancytopenia in propionic acidemia

T2 - Hematologic evaluation and studies of hematopoiesis in vitro

AU - Stork, Linda

AU - Ambruso, Daniel R.

AU - Wallner, Stephen F.

AU - Sambrano, James E.

AU - Moscinski, Lynn C.

AU - Wilson, Harry L.

AU - McCabe, Edward R B

PY - 1986

Y1 - 1986

N2 - This study investigated the hematologic abnormalities of an infant with propionic acidemia and reversible pancytopenia. Light and electron microscopy of her bone marrow revealed severely disturbed cellular morphology with trilineage dysmyelopoiesis, hemophagocyto-sis, and numerous multinucleated histiocytes and megakaryocytes. The effects of her serum and of organic acids associated with propionic acidemia were studied on hematopoiesis in vitro. Mouse erythroid (CFU-E) and granulocyte-monocyte colonies (CFU-GM) were assayed by fibrin clot technique; human CFU-GM were grown in agar culture. The infant's serum reduced mouse CFU-E and CFU-GM by 43 and 32%, respectively, compared with normal human sera, but had no effect on human CFU-GM in our culture system. Buffered propionic acid caused concentration-dependent inhibition of mouse CFU-E and human CFU-GM over a range reported in sera of acutely ill infants with propionic acidemia. Neither cell viability nor subsequent colony formation was diminished by preincubation of bone marrow cells with propionic acid for 48 h. The three other organic acids studied, tiglic acid, 3-OH propionate, and glycine, did not inhibit growth of mouse CFU-E, CFU-GM, or human CFU-GM, and glycine significantly enhanced formation of the latter. Evaluation of the infant's hematologic abnormalities suggests that inhibition of bone marrow proliferation and maturation and, perhaps, shortened red blood cell survival were responsible for her pancytopenia. The studies performed in vitro implicate propionic acid in this hematopoietic dysfunction.

AB - This study investigated the hematologic abnormalities of an infant with propionic acidemia and reversible pancytopenia. Light and electron microscopy of her bone marrow revealed severely disturbed cellular morphology with trilineage dysmyelopoiesis, hemophagocyto-sis, and numerous multinucleated histiocytes and megakaryocytes. The effects of her serum and of organic acids associated with propionic acidemia were studied on hematopoiesis in vitro. Mouse erythroid (CFU-E) and granulocyte-monocyte colonies (CFU-GM) were assayed by fibrin clot technique; human CFU-GM were grown in agar culture. The infant's serum reduced mouse CFU-E and CFU-GM by 43 and 32%, respectively, compared with normal human sera, but had no effect on human CFU-GM in our culture system. Buffered propionic acid caused concentration-dependent inhibition of mouse CFU-E and human CFU-GM over a range reported in sera of acutely ill infants with propionic acidemia. Neither cell viability nor subsequent colony formation was diminished by preincubation of bone marrow cells with propionic acid for 48 h. The three other organic acids studied, tiglic acid, 3-OH propionate, and glycine, did not inhibit growth of mouse CFU-E, CFU-GM, or human CFU-GM, and glycine significantly enhanced formation of the latter. Evaluation of the infant's hematologic abnormalities suggests that inhibition of bone marrow proliferation and maturation and, perhaps, shortened red blood cell survival were responsible for her pancytopenia. The studies performed in vitro implicate propionic acid in this hematopoietic dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=0022448686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022448686&partnerID=8YFLogxK

M3 - Article

C2 - 3737292

AN - SCOPUS:0022448686

VL - 20

SP - 783

EP - 788

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 8

ER -