Objectives: To describe a population of children diagnosed with Kawasaki's disease (KD) in pediatric rheumatology centers of Rio de Janeiro, Brazil, defining the magnitude of the delay period in diagnosing KD and initiating treatment due to confusion with common childhood febrile illnesses and the impact of this delay on the frequency of coronary sequels. Methods: Data analysis from hospital records summarized in a dedicated form, including name, gender, age, date of first recorded clinical signs, date of admission to the specialty service, information about symptoms, clinical evolution, intravenous immunoglobulin (IVIG) use and coronary sequels. Results: Of 125 patients, 63% were males. 40% were under 2 years at diagnosis. Average lapse between earliest signs and KD diagnosis was 12 days (mean fever duration, 14 d). Only 22.4% had a diagnosis of KD before entering the specialty service. For the remainder, initial hypotheses included: bacterial (60%) and viral infections (12%), rheumatological diseases (4%) and adverse vaccination reactions (1.6%). Hence, prevalent febrile illnesses of childhood were major confounding factors. For records (85.6%) mentioning treatment, 46.7% reported IVIG treatment, beginning after day 10 in 23 cases (21.5%). 20 patients (16%) presented coronary sequels, 9 of which were diagnosed late, including 3 given IVIG after day 10, and 6 given no IVIG. We found no significant association between the frequency of coronary sequels and: a) sex; b) age; c) clinical criteria; d) initiation of IVIG treatment (before or after day 10). Conclusions: Common febrile illnesses of childhood often confound the diagnosis of KD.

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Keywordsfatty aldehyde dehydrogenase; ichthyosis; mutation; Sjögren-Larsson syndrome Sjögren-Larsson syndrome (SLS; OMIM 270200) is an autosomal recessive disorder characterized by the presence of pruritic ichthyosis, mental retardation, spastic diplegia or tetraplegia, retinal perimacular 'glistening white dots' and photophobia. 1 SLS is caused by mutations in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH), a microsomal enzyme that catalyses the oxidation of medium-and long-chain aliphatic aldehydes. 2 More than 70 mutations have been identified in this disease.3 Most mutations are unique to each SLS family, but several common mutations have been reported among patients from Europe and the Middle East. In the first molecular genetic analysis of a cohort of patients with SLS from Brazil, we now report a common disease-causing ALDH3A2 mutation, delineate its associated phenotypic spectrum and describe a diagnostic screening test using restriction enzyme digestion. Case and methodsNine patients with SLS from three apparently unrelated Brazilian kindreds native to the south and southeastern part of the country were studied. Patients 1, 2 and 3 were previously reported 4 and were born to consanguineous parents; patients 4, 5 and 6 are sisters and patients 7 and 8 are their cousins. Patient 9 was also born to first cousins. Blood specimens, Total genomic DNA was extracted from blood using standard phenol-chloroform methods. ALDH3A2 exons and their flanking sequences were amplified by polymerase chain reaction (PCR) and sequenced. 2 To detect the c.1108-1G → C mutation more conveniently, exon 8 was digested with DdeI according to the manufacturer's instructions and restriction products separated by agarose gel electrophoresis. ALDH3A2 haplotypes were determined using four intragenic single nucleotide polymorphisms as described. 2 FALDH enzyme activity was measured in cultured skin fibroblasts. 5Results and discussion Biochemical and molecular characterizationAll patients had <10% of normal FALDH enzyme activity in cultured skin fibroblasts ( Table 1). Sequencing of the ALDH3A2 gene revealed a homozygous c.1108-1G → C mutation in intron 7 of all of the affected individuals. Their parents were heterozygous for the mutation, except for the parents of patient 9 who were not tested. The c.1108-1G → C mutation abolishes a DdeI restriction enzyme cut site in the wild-type gene. DdeI digestion of a 275-bp PCR product of exon 8 and its flanking intron 7 sequence yielded a 181-bp fragment from normal control subjects, but a 263-bp fragment from the patients with SLS (Fig. 1b). This constitutes a convenient screening test for the mutation. Haplotype analysis of the ALDH3A2 gene showed that patients from each family were homozygous for haplo-type 1 (see Rizzo et al.2).The c.1108-1G → C mutation alters the splice acceptor site at the junction of intron 7 and exon 8. Like many exons, exon 8 does not end between codons, but rather ends with part of a codon, which is completed when exon 8 is spliced to exon 9...

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