ガラクトース-1-リン酸ウリジルトランスフェラーゼ欠損症

OBJECTIVES: Classical galactosaemia (OMIM #230400) is an inborn error of carbohydrate metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). CASE PRESENTATION: We report a case of a female infant who presented with vomiting, failure to thrive, hepatic transaminitis and a discrepancy between point-of-care (POC) glucometer (Accu-chek® Inform II, Roche Diagnostics, Germany) and capillary blood glucose (ABL90 Flex Plus© blood gas analyser) testing results, raising the suspicion for a diagnosis of classical galactosaemia. This was attributed to suspected analytical interference from markedly elevated blood galactose, due to a known limitation of the POC glucometer specificity for the monosaccharide sugars glucose and galactose. This led to falsely elevated glucose readings on POC glucometer testing in the presence of a high galactose concentration. Reduced GALT enzyme activity and genetic testing subsequently confirmed a diagnosis of classical galactosaemia. CONCLUSIONS: Identification of discrepancies in certain POC glucometers and capillary blood gas or venous glucose measurements by the clinical biochemistry laboratory may indicate POC glucometer interference and raise suspicion for a diagnosis of classical galactosaemia in the newborn setting.

Galactosemias (GALAC) are rare inherited metabolic disorders with highly variable prevalence worldwide. Differences in newborn screening (NBS) implementation, diagnostic methodologies, and population-specific genetic factors contribute to heterogeneity in epidemiological estimates. We aimed to map the estimated global GALAC birth prevalence and explore the role of NBS in shaping epidemiological patterns. A scoping review was conducted following PRISMA-ScR guidelines. Studies reporting prevalence or incidence of GALAC were included regardless of country or screening context. Data were extracted on study design, population characteristics, screening strategies, diagnostic methods, and reported prevalence, standardized to cases per 100,000 live births when possible. Twenty-eight studies were included, predominantly from Europe, Asia, and North America. Birth prevalence estimates ranged widely, from undetected cases in some Asian populations to over 100 cases per 100,000 live births in isolated populations. Most studies reported one-to-five cases per 100,000 live births in regions with established NBS programs. Higher birth prevalence in specific populations was associated with founder effects, genetic isolation, and sociocultural factors including endogamy and consanguinity. Variability was also influenced by screening coverage, study design, and diagnostic approaches. Programs relying solely on biochemical methods showed limitations in detecting non-classical subtypes, while combined or multi-tier strategies improved diagnostic accuracy but affected the birth prevalence estimates through inclusion of variants. GALAC estimated global epidemiology reflects a complex interplay of genetic, demographic, and methodological factors. Standardization of screening strategies and NBS expansion, particularly in underrepresented regions, are essential to improve comparability of epidemiological data and accurately estimate disease burden.

BACKGROUND: Classical galactosemia (CG) is a rare inherited metabolic disorder associated with long-term neurodevelopmental, language, cognitive and psychosocial difficulties. Social-communication problems may overlap clinically with autism spectrum disorder (ASD), but paediatric data based on standardised ASD assessment remain limited. METHODS: The study included 50 children and adolescents aged 6-17 years with confirmed classical galactosemia. Intellectual functioning was assessed using the Stanford-Binet Intelligence Scales, Fifth Edition. Autism spectrum disorder (ASD) symptoms were evaluated using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), Autism Spectrum Rating Scales (ASRS, parent version), Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), as well as comprehensive clinical assessment by a child and adolescent psychiatrist. RESULTS: A clinical diagnosis of ASD was established in 36% of participants. Results indicating ASD symptoms were obtained in 56% of children using MINI-KID, 48% using ADOS-2, and 30% based on overall ASRS scores. Statistically significant moderate negative correlations were found between IQ and ASD symptom severity, particularly in social communication, social-emotional reciprocity, and attention domains. Selected long-term disease-related manifestations (white matter abnormalities and osteopenia/osteoporosis) were more frequent in children with ASD symptoms identified by MINI-KID. CONCLUSIONS: Children and adolescents with classical galactosemia in this clinical cohort frequently presented ASD-related social-communication difficulties, and a substantial proportion met criteria for a clinical ASD diagnosis.

PURPOSE: Speech and language disorders cannot be diagnosed and treated until children are approximately 2-4 years old. To investigate whether these disorders can be prevented, we developed and trialed Babble Boot Camp (BBC), the first proactive sustained intervention starting with precursor skills including cooing and babbling. METHOD: Participants were two randomly assigned groups of 22 infants with classic galactosemia, a metabolic disease with known risks for severe speech and language disorders. One group started BBC at under 6 months of age, and the other started at 15 months of age, both completing BBC at 24 months of age. Coached by a speech-language pathologist in weekly telehealth sessions, caregivers implemented BBC activities and routines daily at home. A typical control group and a group of children with classic galactosemia who received usual care participated as well. All children completed standardized assessments of speech and language at postintervention. RESULTS: Assessment scores showed that BBC was more effective than usual care for both intervention groups. Greatest benefits were seen in the group that started at or before 6 months of age, with a proportion of clinically concerning scores equal to that in the typically developing peers. No effects of sex, genotype, or milk consumption were evident in the outcomes. CONCLUSIONS: Findings motivate a paradigm shift from deficit-based to proactive approaches for infants with classic galactosemia. BBC is extensible to many other disorders, with trials currently underway for infants with Down syndrome and infants born preterm.

INTRODUCTION: Classical galactosemia (CG), caused by galactose-1-phosphate uridylyltransferase (GALT) enzyme deficiency, is associated with premature ovarian insufficiency (POI) and subfertility. The last years, a counseling paradigm shift has been advocated with emphasis on subfertility instead of infertility because spontaneous pregnancy can occur. CASE PRESENTATIONS: We describe two women (aged 26 and 30 years) with genetically confirmed CG and POI, who conceived spontaneously. Both adhered to lifelong galactose-restricted diet and had regular endocrine monitoring. Their pregnancies were uncomplicated and each delivered a healthy infant at term. CONCLUSIONS: These cases are in line with the counseling paradigm shift, with natural conception being possible in CG. Reproductive counselling of girls and women with CG should entail fertility preservation and spontaneous pregnancy. In case of desired pregnancy, a period of two years to attempt conceiving should be advised. AMH is not a reliable prognostic parameter for predicting the reproductive potential in CG.