Clinical and aspartoacylase gene mutation analysis of Canavan disease in a child / 中华神经科杂志

Objective To investigate the clinical and aspartoacylase (ASPA) gene mutation characteristics of Canavan disease.Methods The clinical data of a child with Canavan disease diagnosed by gene detection who visited Children's Hospital Affiliated to Zhengzhou University in June 2018 were reviewed and analyzed.Results A one year and five months old girl presented with psychomotor retrogression,hypermyotonia,and tendon hyperreflexia.The urinary N-acetylaspartic acid levels were significantly higher (66.832 7,more than 60 times that of normal individuals).Magnetic resonance imaging of the brain showed a multiple and symmetrical hyperintense signal changes in the cerebral white matter.Two heterozygous mutations c.79_80del (p.Gly27Arg) and c.554G＞T (p.Gly185Val) were screened by targeted next generation sequencing.The results of Sanger sequencing showed the two mutations were compound heterozygous mutation derived from her father and mother,and the mutation c.554G＞T has never been reported.Conclusions The next generation sequencing can accurately detect ASPA gene mutation as the first choice for the diagnosis of Canavan disease.The mutation c.554G＞T enriches the gene mutation spectrum of Canavan disease.

Clinical Manifestations of Leukodystrophies: A Single Center Study / 대한소아신경학회지

PURPOSE: Leukodystrophies have been defined as inherited metabolic disorders of myelin resulting in abnormal development or progressive destruction of the white matter. This study was performed to investigate the clinical manifestations and treatments of leukodystrophies in a single Korean tertiary center. METHODS: We retrospectively analysed the medical records of patients who had been diagnosed with leukodystrophy from May 1995 to May 2010 at the Asan Medical Center. RESULTS: During the 15-year study period, 36 cases of leukodystrophies were diagnosed with an verage age at symptom presentation of 49 months. Prominent symptoms at presentation were developmental delay (41%) and seizure (25%); however, nystagmus, developmental regression, hearing loss, gait disturbance, visual disturbance, attention deficit, hypotonia, hyperpigmentation, and hemiparesis were also observed. On MRI, periventricular involvement was noted frequently. The most common diagnoses were adrenoleukodystophy (25%), metachromatic leukodystrophy (11%), Krabbe disease (11%), and Pelizaeus-Merzbacher disease (8.3%). No final diagnosis was made in 14 cases (41%). Bone marrow transplantation was performed in 4 patients and showed favorable prognoses. CONCLUSION: Clinical features of leukodystrophies are not specific to diagnosis and most leukodystrophies remain undiagnosed; however, a logical algorithm based on prevalence could aid the laboratory testing. Because early detection and diagnosis is crucial for treatment and prognosis, it is important to have a high index of suspicion and watchful screening of familial history.

A Case of Developmental Delay with Canavan's Disease: A case report

Canavan's disease is a hereditary disease that causes development delay by demyelinization of white matter in brain. The cardinal symptoms of Canavan's disease are head-lag, macrocephaly, developmental delay, blindness, epilepsy and hypotonia. Seven-month old baby delivered by Caesarean section at gestational age 40 weeks was complaining of an inability to keep head up. In past history, he was treated for congenital nystagmus. Chromosomal study was normal. Brain MRI showed delay of myelination of 5 months old. During neurodevelopment treatment in our hospital about development delay, macrocephaly was observed with head circumference 46 cm (90~97 percentile). He couldn't control his head yet. Brain MRI was done when he was 12-month old. There was no myelination in whole brain compared with that of same age group. The peak elevation of N-acetylaspartic acid (NAA) was showed in magnetic resonance spectroscopy (MRS). NAA was detected as high as 29.7 mmol/molCr, we diagnosed him as Canavan's disease. So we reported this case with a brief review of related literatures.

A Case of Canavan Disease

Canavan disease, also known as van Bogaert-Bertrand disease, is a rare autosomal recessive disorder characterized by early an onset and a progressive spongyform degeneration of the brain, associated with an edema of the central nerve system, intramyelinic swelling and neurologic symptoms. This disorder is most prevalent in people of Ashkenazi Jewish descent but has been observed in other ethnic groups. Patients have severe mental retardation, poor head control, macrocephaly and seizures. Canavan disease is caused by the accumulation of N-acetylaspartic acid(NAA) in the brain as the result of a deficiency of aspartoacylase(ASPA) activity. Most children are reported to have the infantile form, becoming symptomatic between three and six month of age, after unremarkable prenatal and perinatal course. We experienced a case of Canavan disease in a six day old female newborn baby, associated with seizure, degeneration of brain white matter and markedly elevated urine N-acetylaspartic acid(NAA) level. So, we report the case with a brief review of the related literature.

PET,MRI and pathologic characteristics of heroin spongiform leukoencephalopathy / 中华神经科杂志

Objective To summarize PET?MRI and pathologic characteristics of heroin spongiform leukoencephalopathy(HSLE). Methods Clinically, 28 cases underwent CT and MRI analysis,in which 2 cases had brain autopsies and 8 cases had brain biopsies. HE, GFAP, Loyez and Congo Red staining were made and observation done through electronic microscope. 4 cases underwent PET analysis. Results The PET, MRI and pathologic characteristics of HSLE showed (1) Spongiform vacuoles degeneration of white matter was pathologically the main morphological change. (2) All the 28 cases had a history of inhalation of heated heroin vapor and abstained from durg. (3) Most cases were described with acute onset characterized by cerebellar signs. (4) PET shows the cortex of the parietal lobe, occipital lobe and cerebellum became thin in 4 cases, while the cerebral white matter had enlarged. (5) Brain CT and MRI revealed extensive symmetric white matter lesions in cerebra and cerebellum. Conclusions Brain CT and MRI revealed extensive symmetric white matter lesions in cerebra and cerebellum. PET has more advantage in judging progress of patient's condition and therapeutic effecacy than MRI. Spongiform vacuoles degeneration of white matter was the main pathological change.