Late-onset Krabbe's Disease (Globoid Cell Leukodystrophy): A case report

Krabbe's disease is a rare autosomal recessive disorder characterized by hemiplegia, paraplegia, ataxia, cortical blindness, and peripheral neuropathy. This disease is caused by deficiency of the lysosomal enzyme galactocerebroside beta-galactosidase(GALC), resulting in demyelination of white matter of brain and peripheral nerve. We reported a 38-year-old female developed a slowly progressive weakness of lower extremities and gait disturbance since age of 10. Neurological examination revealed spastic weakness of both lower extremities, hyperactive deep tendon reflexes and intrinsic muscle atrophy of both hands and feet. Electrophysiologic study showed uniform demyelinating sensorimotor peripheral neuropathy. T2-weighted brain MRI (magnetic resonance imaging) findings revealed symmetric high signal intensity along the bilateral corticospinal tract. The diagnosis of Krabbe's disease was confirmed by finding of markedly reduced GALC activity in leukocyte. We recommended to consider Krabbe's disease in the diagnosis of patients affecting both central and peripheral nervous system.

A Case of Krabbe Disease with Infantile Spasm

Krabbe disease is a rare autosomal recessive disorder clinically characterized by retardation in motor development, prominent spasticity, seizures, and optic atrophy. Pathologically, there are many globoid cells in the white matter, in addition to the lack of myelin and the presence of severe gliosis. Hence Krabbe disease is known as globoid cell leukodystrophy. Biochemically, the primary enzymatic deficiency in Krabbe disease is galactocerebroside beta-galactosidase. Patients with Krabbe disease can be subdivided into the early-onset type and late-onset type, according to the onset of clinical manifestations. Most patients with early-onset type die before their second birthday. We describe a girl with Krabbe disease associated with uncontrolled seizures, which was confirmed with biochemical study and MRI. The clinical findings of this patient included hyperirritability, scissoring of the legs, flexion of arm, and clenching of the fists, and generalized tonic seizures. EEG showed hypsarrhythmia, and MRI demonstrated degenerative white matter changes in bilateral periventricular white matter, posterior rim of internal capsule, basal ganglia and brain stem on T2W1 and FLAIR image. The diagnosis was based on clinical features of progressive neurologic deterioration in conjunction with low galactocerebroside beta-galactosidase activity.

A Case of Krabbe Disease / 대한소아신경학회지

Krabbe disease is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nerve system due to an enzymatic defect of galactocerebroside bata-galactosidase. The patient had typical clinical features of Krabbe disease, with irritability, hypertonicity, failure to thrive, and opisthotonic posturing. A brain MRI demonstrates profound white matter demyelination. The diagnosis of Krabbe disease is suspected on the basis of clinical pictures and confirmed by finding markedly reduced galactocerebroside bata-galactosidase activity in leukocyte or cultured fibroblast. Here we present the first reported case of Krabbe disease in Korea confirmed by decreased activity of galactocerebroside bata-galactosidase enzyme in leukocyte.

Study of Anti-Galactocerebroside and Anti-Sulfatide Antibodies in Leprosy / 나학회지

Peripheral nerve damage in leprosy would be related to the local cell-mediated immune response to mycobacterial antigens and, presumedly, metabolic and biochemical changes of Schwann cell or circulating demyelinating factors and otherwise, autoimmune process would be involved. The neuralipid composing of cholesterol, ethanolamine glycerophosphatide, sphingomyelin, galactocerebroside(GalC), ethanolamine plasmalogen, serine and choline glycerophophatide, sulfatide are abundant in the myelin and have immunogenicity. Especially, GalC and sulfatide are known to play an important role in myelin function and its stability. The study was undertaken to detect the titers of anti-GalC and anti-sulfatide antibodies for the neural destruction mechanism of leprosy. Subjects tested were 53 leprosy patients with polar type consisting of 25 in tuberculoid leprosy(TT) and 28 in lepromatous leprosy(LL). The titeration of the antibody was done in the sera of patients and controls by enzyme-linked immunosorbent assay(ELISA). The results obtained were as follows ; 1. The detection rate of anti-GalC antibody was in 13(24.5%) of the 53 leprosy patients compared with 3(13.0%) of the 23 normal controls. Among the leprosy patients, there was 8(32.0%) in TT and 5(17.9%) in LL. 2. The detection rate of anti-sulfatide antibody was in 24(45.3%) of leprosy patients compared with 7(26.1%) of normal controls. Both types showed almost same rate of 46.4% and 44.0%, respectively. 3. Mean titer of anti-GalC antibody was 18.9+/-17.0EU/ml in leprosy patients and 12.8+/-8.8EU/ml in normal controls, with statistically insignificant level(p>0.05, one-way ANOVA). Among the leprosy patients, mean titer was 24.7+/-20.9EU/ml in TT and 13.8+/-10.5EU/ml in LL, with significance in TT(p0.05). Among the leprosy patients, mean titer was 26.0+/-15.4EU/ml in TT and 24.7+/-14.0EU/ml in LL, which was nearly same quantities in both types. 5. Examinations using Pearson correlation analysis revealed that the association between anti-GalC and anti-sulfatide antibodies was non-specific in LL(r=0.09) and TT(r=0.04). The analysis between duration of illness and anti-GalC antibody was decreasing correlation(r=-0.89, p0.05). In comparison with anti-sulfatide antibody and duration, LL was higher in 41-50 years, while being higher in 31-40 years in TT, but correlation in both types could not be found(r=0.08, -0.06) In conclusion, the anti-GalC and anti-sulfatide antibodies seemed to be related with nerve damage. Hereafter we think that more study for other neural lipid should be investigated

Galactocerebroside mediated transmembrane Ca2+ signalling in U-87 MG cells: Possible involvement of phosphoinositides.

Antibody to galactocerebroside (anti-GalC) has been shown to evoke a Ca2+ response in cultured glioma U-87 MG cells. The rise in [Ca2+]i was due to release of Ca2+ from the intracellular stores and influx through the plasma membrane. The rise in [Ca2+]i was markedly inhibited by neomycin sulphate and phorbol dibutyrate suggesting the involvement of phosphoinositides in Ca2+ mobilization. The Ca2+ response induced by anti-GalC was rapidly desensitized and repeated addition of anti-GalC did not elevate the [Ca2+]i . Heterologous desensitization was observed with bradykinin and adenosine triphosphate. The intracellular Ca2+ store mobilized by anti-GalC appears to be the IP3 sensitive pool of endoplasmic reticulum. The influx of Ca2+ is mediated by a channel. The Ca2+ influx was also prevented by pretreatment of cells with neomycin sulphate or phorbol dibutyrate. We propose that galactocerebroside may be associated with phospholipase C or other proteins linked to the phosphoinositide pathway of transmembrane signalling and anti-GalC activates the breakdown of phosphoinositides and thus mobilizes Ca2+ in U-87 MG cells.

A study on demyelinating effect of galactocerebroside in experimental allergic encephalomyelitis

An experimental allergic encephalomyelitis was induced by bovine myelin basic protein (MBP) and bovine galactocerebroside (GC) on male guinea pigs. Animals were divided into five experimental and one control groups. Among the five experimental groups, three were inoculated with 75 micrograms, 150 micrograms and 300 micrograms of MBP, respectively, to see the dose dependency of demyelination. The fourth group was inoculated with mixture of 75 micrograms of MBP and 180 micrograms of GC and the fifth group with 180 micrograms GC. All inocula was injected intradermally in emulsion state mixed with equal amount of complete Freund adjuvant. Control group was injected with adjuvant only. Clinical symptoms began to appear from 15th day after inoculation and animals were sacrificed on maximum neurologic deficit or 4 to 5 days after the onset of symptoms. Demyelination was observed in 6 out of 8 animals inoculated with MBP/GC mixture, while only 3 out of 24 animals inoculated with various dosage of MBP showed demyelination. The difference was statistically significant. Serum antibodies to MBP and GC were measured by ELISA method. All of the eight animals inoculated with MBP/GC mixture and two animals inoculated with GC had low titer of anti-GC antibodies, while all animals inoculated with MBP, MBP alone or MBP/GC mixture, had high titer of anti-MBP antibodies. Therefor it is concluded that the demyelination is augmented by GC and is not significantly dose-dependent on MBP.

A study on demyelinating effect of galactocerebroside in experimental allergic encephalomyelitis

An experimental allergic encephalomyelitis was induced by bovine myelin basic protein (MBP) and bovine galactocerebroside (GC) on male guinea pigs. Animals were divided into five experimental and one control groups. Among the five experimental groups, three were inoculated with 75 micrograms, 150 micrograms and 300 micrograms of MBP, respectively, to see the dose dependency of demyelination. The fourth group was inoculated with mixture of 75 micrograms of MBP and 180 micrograms of GC and the fifth group with 180 micrograms GC. All inocula was injected intradermally in emulsion state mixed with equal amount of complete Freund adjuvant. Control group was injected with adjuvant only. Clinical symptoms began to appear from 15th day after inoculation and animals were sacrificed on maximum neurologic deficit or 4 to 5 days after the onset of symptoms. Demyelination was observed in 6 out of 8 animals inoculated with MBP/GC mixture, while only 3 out of 24 animals inoculated with various dosage of MBP showed demyelination. The difference was statistically significant. Serum antibodies to MBP and GC were measured by ELISA method. All of the eight animals inoculated with MBP/GC mixture and two animals inoculated with GC had low titer of anti-GC antibodies, while all animals inoculated with MBP, MBP alone or MBP/GC mixture, had high titer of anti-MBP antibodies. Therefor it is concluded that the demyelination is augmented by GC and is not significantly dose-dependent on MBP.