Phenotypic and genetic spectra of galactose mutarotase deficiency: A nationwide survey conducted in Japan.

PURPOSE: Galactose mutarotase (GALM) deficiency was first reported in 2019 as the fourth type of galactosemia. This study aimed to investigate the clinical and genotypic spectra of GALM deficiency. METHODS: This was a questionnaire-based retrospective survey conducted in Japan between February 2022 and March 2023. RESULTS: We identified 40 patients with GALM deficiency in Japan (estimated prevalence: 1:181,835). Four of 38 patients (10.5%) developed cataracts, which resolved with lactose restriction in three out of four patients. Transient transaminitis was the most common symptom (23.1%). All the patients followed lactose restriction; discontinuation of the restriction after infancy did not cause any complications. Moreover, none of the participants experienced long-term complications. Two variants, GALM NM_138801.3: c.294del and c.424G>A, accounted for 72.5% of the identified pathogenic variants. The patients showed moderately elevated blood galactose levels with lactose intake; however, the elevation was lower than that observed in galactokinase deficiency. CONCLUSIONS: GALM deficiency is characterized by a similar but milder phenotype and lower blood galactose elevation than in galactokinase deficiency. Diagnosis and initiation of lactose restriction in early infancy should be essential for prevention of cataracts, especially in cases of irreversible opacity.

Type and duration of emergency recovery work and its longitudinal effects on mental health symptoms among Fukushima Daiichi Nuclear Power Plant workers: The Fukushima NEWS project study.

BACKGROUND: The Fukushima Nuclear Energy Workers' Support study showed the Fukushima nuclear disaster caused psychological distress in the workers, with higher rates of post-traumatic stress responses (PTSR). To understand how the type and duration of emergency recovery work performed immediately following this disaster impacted workers' psychological status, a longitudinal analysis was conducted with 4-year follow-up data since 2011. METHOD: Fukushima Daiichi nuclear power plant workers were assessed annually with general psychological distress (GPD) and PTSR questionnaires between 2011 and 2014. Combined, 697 Fukushima Daiichi plant workers provided baseline GPD and PTSR in 2011 and their record of working days for approximately one month immediately following the disaster. The relationship between type of emergency recovery work, working days immediately following the disaster, and psychological distress over four years was analyzed using a mixed effects logistic regression model. RESULTS: At baseline, GPD and PTSR scores were significantly higher in nuclear power plant workers who worked 3-5 days immediately following the disaster compared to those who worked only 0-2, particularly in the field engineer subgroup. The effect of working days on GPD remained for over a year, and the impact on PTSR remained significant throughout the four years of observation after the disaster. CONCLUSIONS: The Fukushima Daiichi plant field engineers showed significantly higher psychological distress than other workers. The impact of emergency recovery work on psychological distress persisted for over one year, but PTSR in field engineer workers remained significantly elevated four years after the disaster.

Newborn screening for carnitine palmitoyltransferase II deficiency using (C16+C18:1)/C2: Evaluation of additional indices for adequate sensitivity and lower false-positivity.

BACKGROUND: Carnitine palmitoyltransferase (CPT) II deficiency is one of the most common forms of mitochondrial fatty acid oxidation disorder (FAOD). However, newborn screening (NBS) for this potentially fatal disease has not been established partly because reliable indices are not available. METHODS: We diagnosed CPT II deficiency in a 7-month-old boy presenting with hypoglycemic encephalopathy, which apparently had been missed in the NBS using C16 and C18:1 concentrations as indices. By referring to his acylcarnitine profile from the NBS, we adopted the (C16+C18:1)/C2 ratio (cutoff 0.62) and C16 concentration (cutoff 3.0nmol/mL) as alternative indices for CPT II deficiency such that an analysis of a dried blood specimen collected at postnatal day five retroactively yielded the correct diagnosis. Thereafter, positive cases were assessed by measuring (1) the fatty acid oxidation ability of intact lymphocytes and/or (2) CPT II activity in the lysates of lymphocytes. The diagnoses were then further confirmed by genetic analysis. RESULTS: The disease was diagnosed in seven of 21 newborns suspected of having CPT II deficiency based on NBS. We also analyzed the false-negative patient and five symptomatic patients for comparison. Values for the NBS indices of the false-negative, symptomatic patient were lower than those of the seven affected newborns. Although it was difficult to differentiate the false-negative patient from heterozygous carriers and false-positive subjects, the fatty acid oxidation ability of the lymphocytes and CPT II activity clearly confirmed the diagnosis. Among several other indices proposed previously, C14/C3 completely differentiated the seven NBS-positive patients and the false-negative patient from the heterozygous carriers and the false-positive subjects. Genetic analysis revealed 16 kinds of variant alleles. The most prevalent, detected in ten alleles in nine patients from eight families, was c.1148T>A (p.F383Y), a finding in line with those of several previous reports on Japanese patients. CONCLUSIONS: These findings suggested that CPT II deficiency can be screened by using (C16+C18:1)/C2 and C16 as indices. An appropriate cutoff level is required to achieve adequate sensitivity albeit at the cost of a considerable increase in the false-positive rate, which might be reduced by using additional indices such as C14/C3.