HLA DRBI *DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune repsonse to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I seropositive younger son requires close clinical follow-up. (AU)

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older siblings had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents and the development of ATLL in second-generation Caribbean immigrants (AU)

Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis [see comments]

OBJECTIVE -- To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN -- Migrant family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING -- Britain and Jamaica. SUBJECTS -- All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britian (group 2); and index patients' children who were born and resident in Britian (group 3). All had been breast fed and none had had blood transfusions. RESULTS -- Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22 percent (10/46; 95 percent confidence limits 9 to 34 percent) compared with zero among British born offspring (0/14) and was higher in group 2 at 33 percent (7/21; 12 to 55 percent) than in group 1 at greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION -- In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than naternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature (AU)

Multiple lentigines syndrome in Dominica

Multiple Lentigines Syndrome with variable penetrance is described in a Dominican family mild skeletal manifestations, including arachnodactyly, were present with low intellect in the propositus. The syndrome is of importance because of the association with various cardiac abnormalities and deafness. It occurs in black people though the lentigines may be difficult to recognise, and relatives without lentigines may have cardiac abnormalities (AU)

Wilson's disease in the Commonwealth of Dominica: a case report

The first case reported in Dominica of Wilson's disease is described. This is possibly the first successfully treated case in the West Indies. Wilson's disease, though rare, may occur in an unexpected setting.(AU)

A genetic marker for elevated levels of haemoglobin F in homozygous sickle cell disease

Ten patients with sickle cell (SS) disease from a Jamaican family were found to have unusually high levels of haemoglobin F for this population. Each of them has inherited one sickle cell gene on a chromosome characterized by an arrangement of restriction fragment length polymorphisms (haplotype) which is very rare in the Jamaican population. Genetic analysis of the family suggests that there is a determinant linked to the á-globin gene cluster, charaterized by this haplotype, which is responsible for increased haemoglobin F production in response to anaemia. Interestingly this particular haplotype appears to be common in patients with SS disease in eastern Saudi Arabia in whom a high level of haemoglobin F is the rule rather than the exception. Hence it is possible that this haplotype (++-++) acts as a genetic marker for elevated levels of haemoglobin F in sickle cell disease (AU)

Sickle cell-Hb Lepore Boston syndrome: uncommon differential diagnosis to homozygous sickle cell disease

Two siblings assumed on the basis of clinical and hematological evidence to have homozygous sickle cell (SS) disease were found to have a mother without sickle hemoglobin. Subsequent investigation and hemoglobin structural studies indicated the diagnosis to be sickle cell-Hb Lepore Boston syndrome. This syndrome generally manifests clinically significant sickle cell disease, and this genotype should be borne in mind in apparent SS disease where a parent without sickle hemoglobin is discovered.(AU)

The genetics and molecular basis of alpha thalassaemia in association with Hb S in Jamaican Negroes

We have studied seven Jamaican Negro families in whom the genes for O thalassaemia and the sickle cell mutation (ás) were independently segretated. Using a combination of techniques we identified two O thalassaemia phenotypes which resemble the reserve (O thalassaemia 1) and mild (O thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of O thalassaemia with the genotype in this population. Furthermore, since in each family O thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the OO/OO, -O/-O genotype who are also heterozygous for the ás mutation. Genetic analysis in these families shows that in each case subjects with the O thalassaemia 1 phenotype are homozygous for the O thalassaemia 2 defect (-O/-O). We have found no instances of the genotype --/OO in this population which may explain the rarity of the severe O thalassaemia 2 homozygotes from this population shows that the (-O/) haplotype results from a deletion of one of the linked pair of O globin and that this had probably arisen by an unequal crossover between non-homologous O genes (AU)

Hereditary nephritis (with unusual renal histology): report of a first case from the West Indies

A 21-year-old Grenadian girl undergoing investigation in Trinidad for anaemia was diagnosed as a case of hereditary nephritis. She had the clinical features of a nephropathy, nerve deafness and an ocular defect. Renal histology was exceptional in that in addition to the typical findings of a hereditary nephritis, cystic areas generally associated with medullary cystic disease were noted. Several members of the patient's maternal family were afflicted with either deafness, visual disturbances or renal disease.(Summary)

Variations in globin chain synthesis in hereditary persistence of fetal haemoglobin

Globin synthesis was studied in four Negro families including 10 members with Hb A-HPFH and four with Hb S-HPFH. The á/O specific activity ratios in 10 of these patients with Hb A-HPFH heterozygotes were similar to those of the control group. In two patients with Hb A-HPFH, the á/O ratio was slightly decreased in one (0.84) and clearly decreased in another (0.78). In two of the patients with Hb S-HPFH the ratios were clearly decreased (0.71 and 0.75). The extended range of á/O ratios in these 14 patients is similar to that of Negro patients with á-thalassaemia trait. These studies indicate that a decreased á/O ratio may be found in HPFH, as well as in á-thalassaemia. Bone marrow globin synthesis was measured in two patients with Hb S-HPFH and decreased peripheral blood á/O ratios, and in one with Hb A-HPFH and a normal peripheral blood á/O ratio. In each patient the (á+y)/O ratio of radioactivities as well as the á/O specific activity ratio was close to I and therefore balanced, indicating more rapid decay of á-chain synthesis relative to O-chain during red cell maturation or extremely rapid destruction of newly synthesized excess O-chains in the bone marrow.(Summary)

Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia

Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans.Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out. (AU)

Beta-thalassaemia of clinical significance in adult Jamaican negroes

Over a 9-year period, three adult Negro patients with á-thalassaemia of clinical significance were recognized out of approximately 185,000 new adult patients attending the University Hospital. These patients, ages 15-58 years, have clinical and haematological characteristics within the spectrum of á-thalassaemia intermedia; which in this paper refers to phenotypes resulting from defects in á-chain synthesis clinically intermediate between classical Cooley's anaemia and á-thalassaemia trait, genetic classification being dependent on family study. Family studies established the presence of two á-thalassaemia genes conclusively in one case (proposita, family A); presumptively in another(propositus, family C); while in the remaining subject (proposita, famaily B), who has two similarly affected siblings, homozygosity is suspected, but not proven by family study. In simultaneous Fe and Cr studies, estimates of effective erythropoiesis are in reasonable agreement with measurements of red cell destruction.(Summary)

Globin synthesis in the Jamaican Negro with beta-thalassemia

Globin synthesis was studied in three Jamaican Negro families with 18 heterozygotes and 5 homozygotes for beta-thalassemia. Synthesis of the beta chain of Hb A in the peripheral blood of heterozygotes was equal to that of the alpha-chain in 10 patients and was decreased in the remainder. In one patient with Hb C beta-thalassemia the beta/alpha ratio was normal. These findings were similar to those in American Negroes, but differed from those in Caucasian with beta-thalassemia trait, in each of whom the beta/alpha ratio was decreased. Globin synthesis was balanced in the bone marrows of Negro and Caucasian heterozygotes. Despite the milder clinical disease in Negro homozygotes as compared to Caucasian patients, the beta/alpha ratios were similar in both groups. The presence of alpha-thalassemia combined with beta-thalassemia in Negro heterozygotes is not a likely explanation for the high incidence of balanced globin synthesis ratios. The expression of relative beta to alpha chain synthesis in Negro heterozygotes appears to be modified by a factor which is not linked to the delta-chain locus. The nature of this factor is not known at present.(Summary)

Scoliosis with progressive external ophthalmoplegia in four siblings

Four cases are presented of a syndrome of progressive external ophthalmoplegia and scoliosis occurring within one family. These patients were extensively investigated but no biochemical abnormality was detected (AU)

Hemoglobin O Arab in four negro families and its interaction with hemoglobin S and hemoglobin C

Hemoglobin O Arab (O2á2 121 Glu leads to Lys) was found in 25 members of four apparently unrelated Negro families in the West Indian island of Jamaica. In each family the propositus had Hb SO disease. Two cases had been mistakenly diagnosed as Hb SC disease. Two persons heterozygous for both Hb C and Hb O Arab were found in these families, and Hb O Arab á thalassemia in one other relative. The clinical course and symptomatology of Hb SO disease is comparable to that in Hb SD(O2á2 121 Glu leads to GluNH2) disease and more severe than Hb SC disease. In vitro mixtures of Hb O Arab and Hb S change from a liquid to a gel phase at total hemoglobin concentrations weaker than those required to gel pure Hb S, whereas mixtures of Hb C require a stronger total hemoglobin concentration before gelling will occur. Oxygen dissociation studies on red cells containing Hb SO show a homozygous sickle-cell anemia and outside the range for subjects with sickle-cell Hb C disease.(AU)