No abstract

Severe pancytopenia due to azathioprine (AZA) toxicity in patients with autoimmune diseases is not uncommon. We describe a 14‐year‐old girl with HLA‐B27+ spondylarthritis who was treated with AZA 3 mg/kg/day and who suddenly developed severe pancytopenia in the seventh week of treatment. Analysis of the catabolic pathway of AZA revealed a homozygous deficiency of thiopurine methyltransferase (TPMT) on the basis of a combined 2‐point mutation at nucleotide positions 460 and 719 in the gene for TPMT, causing a toxic level of the metabolic active 6‐thioguanine nucleotides (6‐TGN) (2,394 pmoles/8 × 108 red blood cells). The patient was transfusion dependent and finally recovered 8 weeks after the development of the pancytopenia. At that time, 6‐TGN had already returned to normal therapeutic levels. Family studies revealed another homozygous deficiency in the mother, while the other family members were heterozygous.

Interruption of the aortic arch (IAA) is a severe malformation of the heart with known association to DiGeorge syndrome (DGS) and 22q11.2 hemizygosity. The aim of this study was to establish incidence and significance of 22q11.2 hemizygosity in an unbiased sample of patients with IAA. All 15 children with IAA who were referred to our hospital in a 3-year period were tested by chromosome and fluorescence in situ hybridization (FISH) analysis with the probes D22S75, Tuplel, and cHKAD26 and by a set of 10 simple tandem repeat polymorphic (STRP) markers. In nine of 11 children with IAA type B, 22q11.2 hemizygosity was demonstrated by FISH and STRP analysis, but in none of the four children with type A. In all but one child, deletion size was approximately 3 Mb. The girl with the smaller deletion of approximately 1.5 Mb differed because of an Ullrich-Turner syndrome-like phenotype and severe T-cell defect. Additionally, in one patient with phenotypic signs of DGS, a small deletion distal to the known DGS region containing the marker D22S308 was suspected by STRP analysis. One deletion was shown to be inherited from a healthy father and one IAA type A recurred in a sib. T-cell anomalies were evident in eight of the nine children with classical deletion, five of whom suffered also from hypoparathyroidism. With respect to cause and clinical course, IAA type A and B were shown to represent different entities. This study showed that variable symptoms of 22q11.2 hemizygosity may cluster.

Objective-To describe the morphology of the pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries with and without monosomy 22q11. Design-A retrospective analysis of all patients with this congenital heart defect who are being followed at the University Children's Hospital Erlangen. Setting-A tertiary referral centre for paediatric cardiology and paediatric cardiac surgery. Patients-21 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Monosomy 22q11 was diagnosed by fluorescent in situ hybridisation using the D22S75 probe (Oncor). The morphology of the pulmonary arteries was assessed on the basis of selective angiograms. Results-10 patients (48%) were shown to have a microdeletion in 22q11 (group I). There was no diVerence with respect to the presence of confluent central pulmonary arteries between these patients (80%) and the remaining 11 patients (group II) without monosomy 22q11 (91%). Patients of group I, however, more often had arborisation anomalies of the pulmonary vascular bed (90% in group I v 27% in group II). Because of the more severe abnormalities of the pulmonary arteries, a biventricular repair had not been possible in any of the children with monosomy 22q11, though repair had been carried out in 64% of the children in group II. Conclusions-The developmental disturbance caused by monosomy 22q11 seems to impair the connection of the peripheral pulmonary artery segments to the central pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, resulting in a lower probability of biventricular repair. (Heart 1998;79:180-185 In the majority of cases with tetralogy of Fallot and pulmonary atresia, collateral lung perfusion is provided either by a unilateral or bilateral arterial duct or by major aortopulmonary collateral arteries.9 10 According to the findings of Momma et al the presence of major aortopulmonary collateral arteries is associated in a high percentage with monosomy 22q11.2 Among their cohort of 49 patients with pulmonary atresia and ventricular septal defect, monosomy 22q11 was present in 21 of 34 children with collateral lung perfusion by major aortopulmonary collateral arteries.2 The purpose of our study was to determine additional anomalies of the pulmonary vascular bed and to define their impact on the treatment in the subgroup of patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. MethodsAll 21 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries who are at present being followed at our institution were included in this retrospective study. These patients were not strictly consecutive, since several children who had been diagnosed during recent years had been lost to follow up or had died.Metaphase chromosomes of peripheral blood lymphocytes were analysed after GTG banding and b...

Interruption of the aortic arch (IAA) is a severe malformation of the heart with known association to DiGeorge syndrome (DGS) and 22q11.2 hemizygosity. The aim of this study was to establish incidence and significance of 22q11.2 hemizygosity in an unbiased sample of patients with IAA. All 15 children with IAA who were referred to our hospital in a 3-year period were tested by chromosome and fluorescence in situ hybridization (FISH) analysis with the probes D22S75, Tuplel, and cHKAD26 and by a set of 10 simple tandem repeat polymorphic (STRP) markers. In nine of 11 children with IAA type B, 22q11.2 hemizygosity was demonstrated by FISH and STRP analysis, but in none of the four children with type A. In all but one child, deletion size was approximately 3 Mb. The girl with the smaller deletion of approximately 1.5 Mb differed because of an Ullrich-Turner syndrome-like phenotype and severe T-cell defect. Additionally, in one patient with phenotypic signs of DGS, a small deletion distal to the known DGS region containing the marker D22S308 was suspected by STRP analysis. One deletion was shown to be inherited from a healthy father and one IAA type A recurred in a sib. T-cell anomalies were evident in eight of the nine children with classical deletion, five of whom suffered also from hypoparathyroidism. With respect to cause and clinical course, IAA type A and B were shown to represent different entities. This study showed that variable symptoms of 22q11.2 hemizygosity may cluster.