A patient with early-onset globoid cell leukodystrophy / 中国神经精神疾病杂志

We retrospectively analyzed a child with early-onset globoid cell leukodystrophy(Krabbe's disease)caused by complex heterozygous variations in the GALC gene.The girl was admitted to the hospital at the age of 4 month with main complaints of"No obvious cause of milk refusal,poor mental state,drowsiness,convulsions,fever."Brain MRI showed abnormal symmetric signals changes in bilateral cerebellar hemispheres,bilateral internal capsule hind limbs and bilateral ventricles,thin corpus callosum,myelination process lags behind the level of children of the same age.High-throughput sequencing analysis identified compound heterozygous mutations in GALC gene(NM 000153.4):c.[908+1G>A];[194G>A and the two heterozygous mutations were correspondingly inherited from his father and mother,respectively.The application of high-throughput sequencing technology can diagnose Krabbe disease efficiently and accurately,which assists in clinical identification and diagnosis.

Late Infantile-Onset Globoid Cell Leukodystrophy: Treatment using Hematopoietic Stem Cell Transplantation / 대한소아신경학회지

Globoid cell leukodystrophy is a rare autosomal recessive disorder of the brain white-matter caused by galactosylceramidase deficiency; the disorder is classified into four types based on the age of onset. Approximately 80–85% of patients have an early infantile form, while 10–15% has a late infantile form. Globoid cell leukodystrophy leads to a progressive neurological deterioration, and affected patients rarely survive more than 2–3 years. Although many different treatments have been investigated over several decades, further research is still needed. Hematopoietic stem cell transplantation is the standard treatment for globoid cell leukodystrophy. Here, we report a case of symptomatic late-infantile globoid cell leukodystrophy treated with stem cell transplantation. After transplantation, disease progression ceased and cognitive and motor function improved. And a 6 months follow-up study using brain magnetic resonance imaging showed white matter involvement was increased. After that, annual follow-up brain magnetic resonance imaging showed a stable status of disease.

Application of next generation sequencing technology for genetic diagnosis of a case with globoid cell leukodystrophy / 临床儿科杂志

Objective To explore the clinical, radiological features and gene mutation of GALC gene in one child with globoid cell leukodystrophy (Krabbe disease). Methods The clinical and radiological data of a patient diagnosed with Krabbe disease through next-generation sequencing were retrospectively analyzed. Sanger sequencing was used to confirm the results. Results The patient was late infantile form with main manifestations of progressive psychomotor regression and convulsion. Brain MRI showed symmetric long T1 and long T2 signal changes in the white matter next to lateral ventricle angle, posterior limb of internal capsule, and the ministry of corpus callosum. The patient was found to have compound heterozygous mutations of c.1832T>C in exon 15 and c.979T>G in exon 9, which resulted in amino acid changes of p.L611S and p.F327V, respectively. Sanger sequencing results showed that the two heterozygous mutations were correspondingly inherited from his mother and father. Conclusions Next-generation sequencing technology is a useful tool for the detection of GALC gene mutation, which is valuable for definite diagnosis and differential diagnosis of Krabbe disease in clinical practice.

The clinical and genetic features of early-onset globoid cell leukodystrophy in one boy / 临床儿科杂志

Objective To investigate the clinical, biochemical and genetic features of a Chinese boy with early-onset glo-boid cell leukodystrophy (GLD). Methods The clinical and genetic data of a rare case of early-onset GLD were retrospectively analysed. Results At 2 months after birth, the boy showed progressive psychomotor regression. At 4 months of age when the boy was taken to a doctor, the pyramidal sign was positive. The cranial MRI showed that the body of the lateral cerebral ventri-cles was slightly enlarged and the brain ditch crack of frontal-temporal-parietal lobe was widened and deepened. On his brain CT scan, high signals in bilateral basal ganglia, thalami, cerebellar hemisphere were observed.β-galactosylceramidase (GALC) ac-tivity in the peripheral leucocytes was signiifcantly decreased (3.9 nmol/g protein.h). On his GALC gene, one homozygous novel mutation c.868C>T on exon 8 was found, which resulted in the amino acid change on p.R290C proteins. Conclutions Early-on-set GLD is a rare autosomal-recessive hereditary lysosomal storage disease with a terrible prognosis, in which beta-galactose glu-coside enzyme deifciency is induced by GALC gene mutation. The diagnosis of early-onset GLD is dififcult and should depend on enzyme assay and gene testing.