Validity of congenital malformation diagnoses in healthcare claims from a university hospital in Japan.

PURPOSE: This study aimed to assess the validity of diagnoses of congenital malformations (CMs) recorded in claims of a university hospital in Japan. METHODS: Congenital malformations were identified according to Code Q00-Q89 of the International Classification of Diseases, 10th revision. All the children who had been diagnosed with CMs based on their claims in 2015 and within 1 year from their birth month were selected for this study. The infants' medical records were considered as a gold standard. Positive predictive values (PPVs) for CMs were calculated. RESULTS: This study included 227 infants who had a CM diagnosis in their claims. Based on the algorithms established by the Quebec Pregnancy Cohort study group, the PPV for any CM was 90.7% and that for major CMs (MCMs) was 91.5%. Concerning MCMs of specific organ systems, those of the circulatory system (PPV 85.1%) were the most frequent, followed by cleft lip and cleft palate (PPV 100.0%), and other CMs of the digestive system (PPV 96.4%). Based on the EUROCAT classification, the PPV for any MCM was 88.5%. Specific MCMs reported in ≥20 infants were ventricular septal defect (PPV 96.0%), patent ductus arteriosus (PPV 72.7%) and cleft lip with or without cleft palate (PPV 100.0%). CONCLUSIONS: The PPVs for CMs in the Japanese administrative data were high enough to suggest that these data could be utilized for perinatal pharmacoepidemiological evaluations. The results were from a single center, and further validation studies are needed.

Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery.

The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2(-/-) mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2(-/-) keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2(-/-) epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were up-regulated in Aldh3a2(-/-) keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2 As a result, Aldh3a2(-/-) mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2(-/-) mice. In conclusion, Aldh3a2(-/-) mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification.

Aldehyde dehydrogenases (ALDHs) catalyse the conversion of toxic aldehydes into non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2 and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ALDH3B3 have yet to be characterized. In the present study, we examined the enzyme activity, tissue distribution and subcellular localization of ALDH3B2 and ALDH3B3. Both were found to exhibit broad substrate preferences from medium- to long-chain aldehydes, resembling ALDH3A2 and ALDH3B1. Although ALDH3B2 and ALDH3B3 share extremely high sequence similarity, their localizations differ, with ALDH3B2 found in lipid droplets and ALDH3B3 localized to the plasma membrane. Both were modified by prenylation at their C-termini; this modification greatly influenced their membrane localization and enzymatic activity towards hexadecanal. We found that their C-terminal regions, particularly the two tryptophan residues (Trp462 and Trp469) of ALDH3B2 and the two arginine residues (Arg462 and Arg463) of ALDH3B3, were important for the determination of their specific localization. Abnormal quantity and perhaps quality of lipid droplets are implicated in several metabolic diseases. We speculate that ALDH3B2 acts to remove lipid-derived aldehydes in lipid droplets generated via oxidative stress as a quality control mechanism.