Clinical and chromosome studies in Fanconi's aplastic anaemia.

Abstract

A pernicious anaemia-like picture of the peripheral blood associated with congenital abnormalities was first described by Fanconi (1927) Materials and MethodsTwenty ml. of freshly drawn venous blood from each patient was added to 2 ml. of anticoagulant (heparin in dextran) in a sterile container and gently mixed. The erythrocytes were allowed to settle at 370 C., and the supernatant plasma and leucocytes were drawn off. The number of leucocytes per cu. mm. was determined, and for each patient cultures were set up in triplicate making the volume of each culture up to 10 ml. with TC 199 (Glaxo) so that the final concentration of leucocytes was about 106 per ml.Two drops of phytohaemagglutinin P (PHA, Difco) were added to each culture which was then incubated at 370 C. for 72 hours. At this stage 0 2 ml. demecolcine at a concentration of 1 mg./100 ml. of TC 199 was added to each culture; these were then incubated at 370 C. for a further 2 hours. Each culture was then spun down at 2000 r.p.m. for 10 minutes and the supernatant discarded. The cells were resuspended in 3 ml. hypotonic saline, 025°o (w/v), for 15 minutes at 370 C., fixed in acetic alcohol, resuspended in sufficient 4500 acetic acid to give an opalescent suspension, spread on to cold slides, and air-dried. The preparations were then stained with 1000 Giemsa at pH 6-4.

Fanconi's aplastic anaemia with short stature. Absence of response to human growth hormone.

“…Structural abnormalities of the chromosomes were common, involving chromosomes of groups A, B, C, and were present in 5 cells; 3 cells showed isochromatid gaps and breaks and at least orLe cell contained fragments. The chromosome findings were consistent with those previously described in Fanconi's anaemia (Swift and Hirschhom, 1966;Perkins, Timson, and Emery, 1969).…”

Cytogenetics and Fanconi's Anemia: experimental and other studies of a family

“…The absence of endoredupllcation contrasts with the findings of others [11,55,91,115,117], but agrees with that of Schmld [108].…”

“…A number of authors have reported increased endoreduplication In cultured FA cells [11,55,91,108,115,117]. Schmid, however, considers this to be very un common and not at all characteristic [108],…”

“…Congenital anomalies, hematolog ical symptoms, or chromosome aberrations (discussed below) have been observed in non-anemic relatives of PA cases [44,55,91], Van Buchem et_ al. described three PA sibs; one gave birth to a child with severe congen ital abnormalities who died shortly after birth [17].…”

Storage Pool Disease of Platelets in an Infant with Thrombocytopenic Absent Radii (TAR) Syndrome Simulating Fanconi’s Anaemia

“…In FA, however, haematological abnormalities are rarely manifested prior to age 1 year and may appear at any time between ages 1-12 years (10). In addition, the congenital anomalies are multiple and include absence of thumbs (never reported in TAR syndrome) and radius bones, syndactyly, dislocation of the hip bones, hypoplastic kidneys, patchy brown pigmentation of the skin, mental retardation, microcephaly and hypogenitalism (10,11). Abnormalities of platelet function were not re ported in FA.…”