Pathology
ISSN: 0031-3025 (Print) 1465-3931 (Online) Journal homepage: http://www.tandfonline.com/loi/ipat20
Haemoglobin Lepore Washington in An Australian Family A. B. Findlay To cite this article: A. B. Findlay (1976) Haemoglobin Lepore Washington in An Australian Family, Pathology, 8:2, 95-99 To link to this article: http://dx.doi.org/10.3109/00313027609094433
Published online: 06 Jul 2009.
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Date: 28 January 2016, At: 09:58
Pathology (1976), 8, pp. 95-9
HAEMOGLOBIN LEPORE WASHINGTON IN A N AUSTRALIAN FAMILY A. B. FINDLAY
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
Laboratory of Microbiology and Pathology, Brisbane
Summary Haemoglobin Lepore Washington is reported apparently for the first time in a white Australian male. Because some of this patient's family have similar blood changes it is assumed that they also have inherited the disorder.
Haemoglobin Lepore was first detected by Gerald & Diamond (1958a) when these workers, using starch block electrophoresis to study thalassaemia, found an abnormal haemoglobin fraction. In a later publication the same authors named the abnormal fraction haemoglobin Lepore (Gerald & Diamond, 1958b). Baglioni (1965) described the structure of this abnormal haemoglobin which is now called haemoglobin Lepore Washington (or Boston), and in addition, two similar variants have been found. These are haemoglobin Lepore Hollandia (Barnabas & Muller, 1962) and haemoglobin Lepore Baltimore, (Ostertag & Smith, 1969). Each of these abnormal molecules differs from the normal haemoglobin A, molecule in a similar manner, in that they have normal a-chains combined with N terminal residues of the 6 -chain and C terminal residues of the P-chain. The difference between the haemoglobins Lepore is the position of the change-over from the 6 -like sequence to the P-like sequence. In the case of the haemoglobin Lepore Washington this changeover occurs between positions 87 and 116 of the abnormal chain, which, like normal 6 and P-chains, is 146 residues long. Haemoglobin Lepore has been reported among Italians, Greeks, American negroes, Yugoslavs, Turkish Cypriots, Papuans, Indians and Jamaicans (Wintrobe et al., 1974), and to our knowledge has been found only once in a person of British stock, a Scot (Lehmann, 1974; personal communication). This paper reports the finding of haemoglobin Lepore Washington in an Australian male and it appears that some of his children and a grandchild have also inherited the disorder.
CASE REPORTS Patient 1 The propositus The patient was a male aged 54 years, Australian of several generations from British stock. He was referred to this laboratory by his general practitioner who was investigating a
96
Pathology (1976), 8, April
FINDLAY
TABLE1 Laboratory findings in the original patient and three of his relatives Hb Serum Fe W.C.C. (g/IOO ml) (pg/lOO ml) /mm3
Case no.
Details
1
Propositus M, 54 yr
10.8
91
2
Daughter 32 yr
10.4
55
Son
Grandson 2 Yr
___
Hb electrophoresis R.B.C. in blood film & densitometry
-
6,400
Hb - A, : 87% H b - A , : 2% H b - F : 1% Abnormal : 10% band
Mild hypochromia and anisocytosis, moderate microcytosis with occasional elliptocytes, schistocytes, target cells and polychromasia. One nucleated red cell was seen
5.000
Hb - A, 88% H b - A , : 2% Hb- F : trace Abnormal : 10% band
Mild hypochromia, anisocytosis and elliptocytosis Occasional target cells
14.1
8,300
Hb - A, : 88% Hb- A, : 2% Hb - F : trace Abnormal : 10% band
Normochromic, slight anisocytosis, moderate numbers of microcytes, occasional target cells
10.9
6.200
Hb-A :88% Hb- A, : 2% Hb- F : trace Abnormal : 10% band
Mild hypochromia and anisocytosis. Occasional elliptocytes, schistocytes, irregularly contracted cells and target cells.
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
~~
__
3
-
4
complaint of painful joints. The patient claimed to have had good health all his life apart from these pains which were diagnosed as being caused by rheumatoid arthritis thirty years previously. He was pale at the time of attendance at this laboratory. There was no clinical history or evidence of bleeding and his spleen was not palpable. The main laboratory findings are shown in Table 1. The R.A. test was negative and the reticulocyte count was 6%. The result of cellulose acetate haemoglobin electrophoresis (Golias, 197l), and subsequent densitometry of the fractions are also shown. The abnormal band travelled cathodal to Hb-F (Fig. 1). Chemical analysis performed at the laboratory of the Medical Research Council’s abnormal haemoglobin unit, showed the abnormal fraction to be haemoglobin Lepore Washington. Patient 2 A daughter of the propositus attended the laboratory on request. She was an Australian aged 32 years and gave a history of anaemia for most of her life which she claimed had been treated intermittently with both parenteral and oral iron. Laboratory findings are seen in Table 1. In this case and those following, it was assumed that the abnormal band was haemoglobin Lepore Washington. Patient 3 A son of the propositus did not attend the laboratory but had a blood sample forwarded. No clinical history is available. The laboratory findings are listed in Table I .
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
HAEMOGLOBIN LEPORE
97
FIG. 1 Cellulose acetate haemoglobin electrophoresis showing an abnormal
band cathodal to Hb-F in two cases. Normal adult and cord + adult blood are also included
Patient 4 This patient, son of patient 2 and therefore a grandson of the propositus, was a 12-year-old Australian male. His mother thought that he had appeared to be pale for most of his life but anaemia had never been diagnosed. The laboratory findings are shown in Table 1.
DISCUSSION Abnormal haemoglobin conditions are referred to collectively as being autosomal codominant inheritants. In this family, all of those affected, except one, had mild anaemia, and all had similar red cell changes to those of the propositus. In each case the abnormal haemoglobin (Lepore Washington) comprised 10% of the total haemoglobin content, the same figure approximated by Wintrobe et al. (1974) when electrophoresis was used as the method of separation. Other consistent findings in all of the affected patients were the presence of small amounts of haemoglobin F and borderline low levels of haemoglobin A,. Only the offspring of the propositus who had inherited the abnormal gene have been discussed. The full genetic picture as far as can be ascertained is shown in Fig. 2.
98
FINDLAY
Pathology (1976), 8, April
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
Propositus
0 Affected 0 Unaffected A Not tested
I FIG. 2 Pedigree of the family
ACKNOWLEDGEMENTS The author wishes to express his appreciation to Professor H. Lehmann and Dr R. Casey, Medical Research Council, Cambridge for carrying out the chemical analysis of the abnormal haemoglobin fraction. Thanks are also due to Dr A. Semple, Brisbane for permission to publish detains of his patient (the propositus) and to Dr H. Smith, Royal Brisbane Hospital for confirming the initial findings using starch gel electrophoresis. ADDENDUMAfter this article was accepted for publication Wilkinson et (11. (1975) have made a similar report. Address for reprint requests: A.B.F., Haematology Department, Laboratory of Microbiology and Pathology, 63-79 George Street, Brisbane, Queensland 4000, Australia
Ref ere nces BAGLIONI,C. (1965): Abnormal human haemoglobins X. A study of haemoglobin Lepore Boston. Biochim. biophys. Acta (Amst.). 97, 31-46.
BARNABAS,J. & MULLER,C. J. (1962): Haemoglobin Lepore (Hollandia). Nature (Lond.). 194,931-932.
H A E M O G L O B I N LEPORE
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
GERALD,P. S. & DIAMOND,L. K. (1958a): The diagnosis of thalassaemia trait by starch block electrophoresis of the haemoglobin. Blood. 13, 61-69. GERALD,P. S. & DIAMOND, L. K. (1958b): A new hereditary haemoglobinopathy (the Lepore trait) and its interaction with thalassaemia trait. Blood. 13, 835-844. GOLIAS, T. L. (1971): Helena Laboratories Manual. OSTERTAG, W. & SMITH,E. W. (1969): Haemoglobin Lepore Baltimore a third type of 6 f3 crossover (650f3*6). Europ. J . Biochem. 10, 371-376.
99
WILKINSON, T., GOUGH,P., OWEN,M. C. er al. (1975): The isolation and identification of Haemoglobin Lepore Boston (Washington) in an Australian family. Med. J . Aust. 2, 695-730. WINTROBE, M. M., LEE,R. G., BOGGS, D. R. et al. (1974) : Clinical Haemarology. Lea and Febiger, Philadelphia.
ISSN: 0031-3025 (Print) 1465-3931 (Online) Journal homepage: http://www.tandfonline.com/loi/ipat20
Haemoglobin Lepore Washington in An Australian Family A. B. Findlay To cite this article: A. B. Findlay (1976) Haemoglobin Lepore Washington in An Australian Family, Pathology, 8:2, 95-99 To link to this article: http://dx.doi.org/10.3109/00313027609094433
Published online: 06 Jul 2009.
Submit your article to this journal
Article views: 2
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipat20 Download by: [Universität Osnabrueck]
Date: 28 January 2016, At: 09:58
Pathology (1976), 8, pp. 95-9
HAEMOGLOBIN LEPORE WASHINGTON IN A N AUSTRALIAN FAMILY A. B. FINDLAY
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
Laboratory of Microbiology and Pathology, Brisbane
Summary Haemoglobin Lepore Washington is reported apparently for the first time in a white Australian male. Because some of this patient's family have similar blood changes it is assumed that they also have inherited the disorder.
Haemoglobin Lepore was first detected by Gerald & Diamond (1958a) when these workers, using starch block electrophoresis to study thalassaemia, found an abnormal haemoglobin fraction. In a later publication the same authors named the abnormal fraction haemoglobin Lepore (Gerald & Diamond, 1958b). Baglioni (1965) described the structure of this abnormal haemoglobin which is now called haemoglobin Lepore Washington (or Boston), and in addition, two similar variants have been found. These are haemoglobin Lepore Hollandia (Barnabas & Muller, 1962) and haemoglobin Lepore Baltimore, (Ostertag & Smith, 1969). Each of these abnormal molecules differs from the normal haemoglobin A, molecule in a similar manner, in that they have normal a-chains combined with N terminal residues of the 6 -chain and C terminal residues of the P-chain. The difference between the haemoglobins Lepore is the position of the change-over from the 6 -like sequence to the P-like sequence. In the case of the haemoglobin Lepore Washington this changeover occurs between positions 87 and 116 of the abnormal chain, which, like normal 6 and P-chains, is 146 residues long. Haemoglobin Lepore has been reported among Italians, Greeks, American negroes, Yugoslavs, Turkish Cypriots, Papuans, Indians and Jamaicans (Wintrobe et al., 1974), and to our knowledge has been found only once in a person of British stock, a Scot (Lehmann, 1974; personal communication). This paper reports the finding of haemoglobin Lepore Washington in an Australian male and it appears that some of his children and a grandchild have also inherited the disorder.
CASE REPORTS Patient 1 The propositus The patient was a male aged 54 years, Australian of several generations from British stock. He was referred to this laboratory by his general practitioner who was investigating a
96
Pathology (1976), 8, April
FINDLAY
TABLE1 Laboratory findings in the original patient and three of his relatives Hb Serum Fe W.C.C. (g/IOO ml) (pg/lOO ml) /mm3
Case no.
Details
1
Propositus M, 54 yr
10.8
91
2
Daughter 32 yr
10.4
55
Son
Grandson 2 Yr
___
Hb electrophoresis R.B.C. in blood film & densitometry
-
6,400
Hb - A, : 87% H b - A , : 2% H b - F : 1% Abnormal : 10% band
Mild hypochromia and anisocytosis, moderate microcytosis with occasional elliptocytes, schistocytes, target cells and polychromasia. One nucleated red cell was seen
5.000
Hb - A, 88% H b - A , : 2% Hb- F : trace Abnormal : 10% band
Mild hypochromia, anisocytosis and elliptocytosis Occasional target cells
14.1
8,300
Hb - A, : 88% Hb- A, : 2% Hb - F : trace Abnormal : 10% band
Normochromic, slight anisocytosis, moderate numbers of microcytes, occasional target cells
10.9
6.200
Hb-A :88% Hb- A, : 2% Hb- F : trace Abnormal : 10% band
Mild hypochromia and anisocytosis. Occasional elliptocytes, schistocytes, irregularly contracted cells and target cells.
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
~~
__
3
-
4
complaint of painful joints. The patient claimed to have had good health all his life apart from these pains which were diagnosed as being caused by rheumatoid arthritis thirty years previously. He was pale at the time of attendance at this laboratory. There was no clinical history or evidence of bleeding and his spleen was not palpable. The main laboratory findings are shown in Table 1. The R.A. test was negative and the reticulocyte count was 6%. The result of cellulose acetate haemoglobin electrophoresis (Golias, 197l), and subsequent densitometry of the fractions are also shown. The abnormal band travelled cathodal to Hb-F (Fig. 1). Chemical analysis performed at the laboratory of the Medical Research Council’s abnormal haemoglobin unit, showed the abnormal fraction to be haemoglobin Lepore Washington. Patient 2 A daughter of the propositus attended the laboratory on request. She was an Australian aged 32 years and gave a history of anaemia for most of her life which she claimed had been treated intermittently with both parenteral and oral iron. Laboratory findings are seen in Table 1. In this case and those following, it was assumed that the abnormal band was haemoglobin Lepore Washington. Patient 3 A son of the propositus did not attend the laboratory but had a blood sample forwarded. No clinical history is available. The laboratory findings are listed in Table I .
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
HAEMOGLOBIN LEPORE
97
FIG. 1 Cellulose acetate haemoglobin electrophoresis showing an abnormal
band cathodal to Hb-F in two cases. Normal adult and cord + adult blood are also included
Patient 4 This patient, son of patient 2 and therefore a grandson of the propositus, was a 12-year-old Australian male. His mother thought that he had appeared to be pale for most of his life but anaemia had never been diagnosed. The laboratory findings are shown in Table 1.
DISCUSSION Abnormal haemoglobin conditions are referred to collectively as being autosomal codominant inheritants. In this family, all of those affected, except one, had mild anaemia, and all had similar red cell changes to those of the propositus. In each case the abnormal haemoglobin (Lepore Washington) comprised 10% of the total haemoglobin content, the same figure approximated by Wintrobe et al. (1974) when electrophoresis was used as the method of separation. Other consistent findings in all of the affected patients were the presence of small amounts of haemoglobin F and borderline low levels of haemoglobin A,. Only the offspring of the propositus who had inherited the abnormal gene have been discussed. The full genetic picture as far as can be ascertained is shown in Fig. 2.
98
FINDLAY
Pathology (1976), 8, April
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
Propositus
0 Affected 0 Unaffected A Not tested
I FIG. 2 Pedigree of the family
ACKNOWLEDGEMENTS The author wishes to express his appreciation to Professor H. Lehmann and Dr R. Casey, Medical Research Council, Cambridge for carrying out the chemical analysis of the abnormal haemoglobin fraction. Thanks are also due to Dr A. Semple, Brisbane for permission to publish detains of his patient (the propositus) and to Dr H. Smith, Royal Brisbane Hospital for confirming the initial findings using starch gel electrophoresis. ADDENDUMAfter this article was accepted for publication Wilkinson et (11. (1975) have made a similar report. Address for reprint requests: A.B.F., Haematology Department, Laboratory of Microbiology and Pathology, 63-79 George Street, Brisbane, Queensland 4000, Australia
Ref ere nces BAGLIONI,C. (1965): Abnormal human haemoglobins X. A study of haemoglobin Lepore Boston. Biochim. biophys. Acta (Amst.). 97, 31-46.
BARNABAS,J. & MULLER,C. J. (1962): Haemoglobin Lepore (Hollandia). Nature (Lond.). 194,931-932.
H A E M O G L O B I N LEPORE
Downloaded by [Universität Osnabrueck] at 09:58 28 January 2016
GERALD,P. S. & DIAMOND,L. K. (1958a): The diagnosis of thalassaemia trait by starch block electrophoresis of the haemoglobin. Blood. 13, 61-69. GERALD,P. S. & DIAMOND, L. K. (1958b): A new hereditary haemoglobinopathy (the Lepore trait) and its interaction with thalassaemia trait. Blood. 13, 835-844. GOLIAS, T. L. (1971): Helena Laboratories Manual. OSTERTAG, W. & SMITH,E. W. (1969): Haemoglobin Lepore Baltimore a third type of 6 f3 crossover (650f3*6). Europ. J . Biochem. 10, 371-376.
99
WILKINSON, T., GOUGH,P., OWEN,M. C. er al. (1975): The isolation and identification of Haemoglobin Lepore Boston (Washington) in an Australian family. Med. J . Aust. 2, 695-730. WINTROBE, M. M., LEE,R. G., BOGGS, D. R. et al. (1974) : Clinical Haemarology. Lea and Febiger, Philadelphia.
