Ken Momosaki

Prenatal diagnosis of Gaucher disease using next-generation sequencing.

In the prenatal diagnosis of Gaucher disease (GD), glucocerebrosidase (GBA) activity is measured with fetal cells, and gene analysis is performed when pathogenic mutations in GBA are identified in advance. Herein is described prenatal diagnosis in a family in which two children had GD. Although prior genetic information for this GD family was not obtained, next‐generation sequencing (NGS) was carried out for this family because immediate prenatal diagnosis was necessary. Three mutations were identified in this GD family. The father had one mutation in intron 3 (IVS2 + 1), the mother had two mutations in exons 3 (I[‐20]V) and 5 (M85T), and child 1 had all three of these mutations; child 3 had none of these mutations. On NGS the present fetus (child 3) was not a carrier of GD‐related mutations. NGS may facilitate early detection and treatment before disease onset.

Plasma exchange and chelator therapy rescues acute liver failure in Wilson disease without liver transplantation.

Wilson disease (WD) in patients with a New Wilson Index (NWI) score ≥ 11 is fatal, and these patients are good candidates for liver transplantation (LT). However, plasma exchange and chelator therapy are indispensable and effective even for WD with a score ≥ 11. Moreover, continuous hemodiafiltration (CHDF) with these treatments is essential for acute liver failure (ALF) in WD with hepatic encephalopathy because CHDF can exclude toxic metabolites that may cause damage to the brain. Here, we describe four rescued patients presenting with ALF in WD and discuss the available treatment options.

Liver transplantation may prevent neurodevelopmental deterioration in high-risk patients with urea cycle disorders

UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living‐donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non‐LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non‐transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset.

High-risk screening for Gaucher disease in patients with neurological symptoms

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the deficiency of glucocerebrosidase enzyme activity. Clinical phenotypes of GD are categorized into three groups: (i) non-neuronopathic GD (type 1), (ii) acute neuronopathic GD (type 2) and (iii) subacute neuronopathic GD (type 3). The high-risk screening of neuronopathic GD has been performed using an enzymatic assay on the dried blood spot (DBS) samples. We enrolled a total of 102 individuals (47 females, 55 males; 0–57 years old; median age 10.5 years) with various neurological symptoms. We detected two patients with very low enzyme activity and they were diagnosed with the disease by using glucocerebrosidase gene analysis. Patient 1 was found to be compound heterozygous for the p.R159W/p.R170C locus and patient 2 was found to harbor two mutations at the IVS7+1G>T (c.999+1G>T) and p.L483P sites. This simple screening protocol using DBS samples is useful for early diagnosis of GD in high-risk and underdiagnosed patients suffering from various neurological symptoms.

Amelioration by glycine of brain damage in neonatal rat brain following hypoxia–ischemia

Glycine protected adult brains against injury in an experimental model of stroke, but, because the ischemic response of neonatal brains differs from that of adult brains, we examined the neuroprotective efficacy of glycine and associated mechanisms in an experimental model of neonatal hypoxic–ischemic (HI) encephalopathy.

A Sporadic Case of Fabry Disease Involving Repeated Fever, Psychiatric Symptoms, Headache, and Ischemic Stroke in an Adult Japanese Woman.

Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. This case suggests that Fabry disease should be considered in young patients who exhibit central nervous system symptoms such as ischemic stroke, even if there is no family history of the condition. The episodes of aseptic meningitis and stroke experienced by our patient suggest that persistent inflammation might be the mechanism underlying Fabry disease.