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 3 out of 4 patients. Transient transaminitis was the most common symptom (23.1%). All of 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. CONCLUSION: 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.

Home High-Flow Nasal Cannula Therapy in Children with Congenital Heart Disease.

High-flow nasal cannula (HFNC) therapy has been applied in the perioperative respiratory care for children with congenital heart disease and respiratory problems. However, the information about the feasibility of home HFNC therapy remains lacking among them. We retrospectively reviewed 5 children with congenital heart disease and respiratory problems who underwent home HFNC therapy, and evaluated their feasibility and safety. Age and weight at the introduction of home HFNC therapy were 19 (2-119) months and 5.3 (3.1-11.4) kg, respectively. All subjects had chromosomal anomaly including trisomy 18 in 3 and trisomy 21 in 2 subjects. Cardiac diagnoses included ventricular septal defect in 3, tetralogy of Fallot with complete atrioventricular septal defect in one, and pulmonary atresia with ventricular septal defect in another subject. Other comorbidities involved pulmonary hypertension in 4, micrognathia in 4, West syndrome in one, and bronchial asthma in one subject. Respiratory manifestations involved cyanosis due to upper airway obstruction in 2 and central hypopnea in 2, and recurrent pneumonia in one subject. After home HFNC therapy, systemic oxygen saturation significantly increased from 60 (40-78)% to 83 (83-96)% (P = 0.04), while heart rate and blood partial pressure of carbon dioxide were significantly decreased. There was no adverse event relevant to home HFNC during the follow-up period of 12 (5-49) months. Among them, one patient subsequently underwent tracheotomy at 11 years of age, and two patients weaned to conventional home oxygen therapy at 7 and 23 months of age. Home HFNC is safe and feasible in children with congenital heart disease and respiratory problems.

Focal segmental glomerulosclerosis in patients after Fontan operation: is this a Fontan-associated renal disease?

Despite acceptable survival for Fontan operation, there are concerns about late complications affecting the major organs. We herein present two cases of adults after Fontan operation who developed focal segmental glomerulosclerosis. These cases suggest that focal segmental glomerulosclerosis is owing to haemodynamic incompetence associated with Fontan operation, including congestion, hypoxia, and hyperviscosity, which may be called Fontan-associated renal disease.

Tuberous sclerosis with infantile spasm and subependymal giant cell astrocytoma.

Tuberous sclerosis complex (TSC) is a genetic disease affecting many organ systems and showing different symptoms in each age group. We encountered a TSC patient with intractable epilepsy who had brain tumors suspected to be subependymal giant cell astrocytoma (SEGA). We used adrenocorticotropic hormone and ordinal antiepileptic drugs at first, but they showed limited effectiveness. After we tried several treatments for epilepsy, we started to use everolimus to prevent tumor growth. As a result, the development of the tumor stopped and the epileptic attack improved simultaneously. The frequency and duration of each epileptic spasm and seizure became milder, and the electroencephalogram findings also improved. The mental development had regressed when the epilepsy started, but it started to progress again after the epileptic attack disappeared. Everolimus may be used for treatment of intractable epilepsy with TSC in patients with a growing SEGA.

A case of Potter sequence with WT1 mutation.

Wilms tumor 1 (WT1) is the causative gene of Denys-Drash syndrome and Frasier syndrome, and in most cases, kidney failure develops after birth. We report an unusual case of Potter sequence due to fetal nephropathy and kidney failure with a WT1 mutation. The neonate was born at 37 weeks of gestation, and had no distinctive facial appearance or anomalies of the extremities. The external genitalia were ambiguous. Presence of a penile-like structure or hypertrophic clitoris was noted, and the urethra opened at the base of the penis or clitoris. On ultrasonographic examination, the kidney sizes were small. No kidney cysts were noted, but the kidney parenchymal luminosity was increased. Although the neonate received mechanical ventilation because of severe retractive breathing after birth, he died of poor oxygenation due to air leak syndrome at 60 h after birth. The congenital anomalies of the kidney and urinary tract (CAKUT) gene panel revealed a heterozygous missense mutation in WT1 [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)]. In WT1, missense mutations are associated with earlier onset of nephropathy than nonsense or splicing mutations. However, severe cases of fetal onset and early neonatal death with WT1 mutations are rare, and only one severe case with the same missense mutation in WT1 has been reported. Therefore, WT1 mutation may be suspected in Potter sequence patients with external genital abnormalities, and the WT1 missense mutation in our case [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)] may indicate a severe case with fetal onset of nephropathy and kidney failure.

Limbic Encephalitis following Guillain-Barré Syndrome Associated with Mycoplasma Infection.

A 12-year-old girl was admitted to the authors' hospital due to muscle weakness, gait disturbance, dysarthria, dysphagia, and diplopia. She experienced prodromal fever 10 days before admission. On examination, deep tendon reflex was absent in the extremities, and nerve conduction velocity was decreased in the ulnar nerve. She was diagnosed with Guillain-Barré syndrome (GBS). Despite steroid pulse therapy following administration of intravenous high-dose γ-globulin, clinical manifestations remained unchanged. Therefore, plasma exchange was performed on day 10 of the illness. The titer of serum Mycoplasma immunoglobulin M level was increased. Immunological testing was positive for serum anti-galactocerebroside C antibody. On day 18 of the illness, however, she developed generalized convulsion. Brain magnetic resonance imaging revealed high intensity in the medial temporal lobes, including the hippocampus and thalamus on T2-weighted intensity imaging, which was consistent with limbic encephalitis. Further immunological tests revealed positivity for anti-N-methyl-D-aspartate-type glutamate receptor antibody in the cerebrospinal fluid. She was treated with additional plasma exchange; however, she exhibited residual manifestations including short-term memory disorder, emotional incontinence, and convulsions. This article describes a notable case of limbic encephalitis following GBS associated with prodromal Mycoplasma infection. It is interesting that autoimmune encephalopathy is concomitant with autoimmune polyneuropathy subsequent to Mycoplasma infection.

Infliximab Therapy and the Central Nervous Demyelination in Patients with Kawasaki Disease.

We performed brain magnetic resonance imaging in 14 patients with Kawasaki disease who were treated with infliximab (IFX) at 56 months of age (32-62 months of age) and 23 months (5-35 months) after IFX therapy. Magnetic resonance imaging showed no finding of the central nervous demyelination. IFX therapy is not related to central nervous demyelination in patients with Kawasaki disease.