Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.

Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.

Transient erythroblastopenia of childhood in Sweden: incidence and findings at the time of diagnosis.

All cases of transient erythroblastopenia in children less than 10 years of age, diagnosed in Sweden during the years 1987-89, were identified. Almost all (51/53) were less than 3 years of age. In this group, the incidence was 4.3/100 000, which is the same as that of acute lymphatic leukaemia. No geographical, but a possible temporal, cluster was seen in 1989. The anaemia was severe in some cases; haemoglobin concentration was less than 40 g/l in 8 of 53 children. Thrombocytosis and neutropenia were common and were attributed to high endogenous erythropoietin activity. Thirty-seven of 53 children were given a blood transfusion. All children recovered and no complications or relapses were seen. Transient erythroblastopenia of childhood is a benign disease, and it is important to make a correct diagnosis to prevent unnecessary anxiety for leukaemia or aplastic anaemia.

Transient red cell aplasia in siblings: a common environmental or a common hereditary factor?

During the years 1987-89, transient erythroblastopenia of childhood was diagnosed in 52 previously healthy Swedish children aged less than 4 y. Among these children there were four pairs of siblings, including one pair of identical female twins. This is a much higher familial occurrence than expected. The probability of finding 4 pairs of siblings with this disease in 50 families was estimated to be considerably less than 10-6. In the retrospectively analysed material, no environmental factor was implicated and no association with human leucocyte antigen could be proven. The twins demonstrated the disease simultaneously. Their anaemia was transient and did not recur, but showed certain features usually seen in congenital hypoplastic anaemia. The other pairs of siblings fulfilled the criteria for transient erythroblastopenia of childhood and several years elapsed between the development of the disease in siblings. Two of the fathers were reported to have had transient anaemia during their childhood. Our findings indicate that transient erythroblastopenia of childhood may involve hereditary factors, eventually demonstrating an autosomal dominant inheritance.

Sequential combined spinal epidural block versus spinal block for cesarean section: effects on maternal hypotension and neurobehavioral function of the newborn.

Sequential combined spinal-epidural (CSE) block was compared with spinal block for elective cesarean section. The quality of surgical analgesia and the effect on maternal blood pressure and neonatal neurobehavioral function were evaluated. Forty-two healthy parturients were randomly divided into a spinal (n = 21) and a sequential CSE (n = 21) group. A T4 sensory block was targeted. In the spinal group, 0.5% hyperbaric bupivacaine, 2.5 mL, was injected into the subarachnoid space through a 26-gauge Quincke needle. In the sequential CSE group, 1.5 mL of 0.5% hyperbaric bupivacaine was injected into the subarachnoid space through a long 26-gauge Quincke needle, which was introduced through an 18-gauge Tuohy needle. An epidural catheter was then inserted. If the block in the sequential CSE group did not reach the T4 level in 15 min, it was extended by fractionated doses of 0.5% bupivacaine administered through the epidural catheter. Ephedrine, 10 mg intravenously (i.v.), was given to treat hypotension (20% decrease from baseline value and/or systolic blood pressure below 100 mmHg). The time intervals from induction of block to start of surgery and to delivery were shorter in the spinal group (P < 0.01). Cephalad spread of block (pinprick) 15 min after induction was T4 [T2-T7] (median [range]) in the spinal group and T7 [T2-L1] in the sequential CSE group (P < 0.05). All patients in the sequential CSE group needed epidural bupivacaine, 53.8 +/- 6.5 mg (mean +/- SEM). The surgical analgesia was good or excellent in both groups before delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation.

A 7 year old girl is described with congenital hypoplastic anaemia (Diamond-Blackfan anaemia, DBA) and an apparently balanced reciprocal translocation, 46,XX,t(X;19)(p21;q13). The girl has associated features including short stature, unilateral kidney hypoplasia, and a branchial cyst. Fluorescent in situ hybridisation (FISH) studies with 19q specific cosmids showed that the chromosome 19 breakpoint is located between the RYR1 and the XRCC11 loci spanning a physical region of 5 Mb. There is no family history of DBA and the parents and two healthy sibs have normal karyotypes. This is the first report of a balanced translocation associated with DBA and we suggest that the distinct phenotype has resulted from a de novo disruption of a functional gene. DBA can be inherited as an autosomal trait and our observation may indicate a candidate gene for the disorder in the 19q13 region.

Increased prevalence of overweight in adolescent girls with type 1 diabetes mellitus.

Height and weight were measured in young patients with type 1 diabetes up to the age of 22 y. We found no difference between birth length standard deviation scores (SDS), final height SDS and target height SDS. The study group of 89 diabetic boys and girls did not differ in final height from age- and sex-matched healthy controls. SDS for height at diagnosis, +0.17 +/- 1.10, exceeded that for final height, -0.06 +/- 0.97 (p = 0.037). Height SDS decreased between the ages of 11 and 18 (p < 0.01). In diabetic girls, but not boys, final height SDS was significantly related to mean HbA1c during puberty (r = -0.40; p = 0.025). Weight gain occurred from age of menarche in girls with type 1 diabetes. At the age of 18, diabetic girls were 6.5 kg heavier and had 2.7 kg/m2 higher body mass index (BMI) than control girls (p < 0.001). Diabetic boys were not heavier than control boys. There was a significant relationship between mean HbA1c during puberty and BMI at the age of 18 in diabetic girls (r = 0.47; p = 0.009). In diabetic females, body weight remained unchanged, HbA1c improved and the dose of insulin was significantly reduced between 18 and 22 y of age. The HbA1c improvement was most marked in patients with poor metabolic control. In conclusion, although mean final height was normal in young patients with type 1 diabetes, growth was increased before diagnosis and pubertal growth spurt was reduced. Adolescent overweight was overrepresented; it related to poor metabolic control in females with diabetes, but showed no further acceleration in early adulthood.