Hereditary branching enzyme dysfunction in adult polyglucosan body disease: A possible metabolic cause in two patients

Lossos, Alexander; Barash, V.; Soffer, Dov; Argov, Zohar; Gomori, Moshe; Ben-Nariah, Ziva; Abramsky, Oded; Steiner, Israel

doi:10.1002/ana.410300505

Cited by 81 publications

(67 citation statements)

References 32 publications

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“…Enzymatically, except for adult polyglucosan body disease (15,16), most GSD-IV patients have what appears to be a generalized enzyme defect. The deficiency of GBE activity and the accumulation of amylopectin can be demonstrated in almost all tissues studied, including liver, heart, skeletal muscle, brain, leukocytes, and fibroblasts (5, 9, 12).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the hepatic form, a neuromuscular form of the disease has been reported. These patients may ( a ) present at birth with severe hypotonia, muscle atrophy, and neuronal involvement with death in the neonatal period (8)(9)(10)(11); ( b ) present in late childhood with myopathy or cardiopathy (12)(13)(14); or ( c ) present as adults with diffuse central and peripheral nervous system dysfunction accompanied by accumulation of polyglucosan bodies in the nervous system (so-called adult polyglucosan body disease) (15,16).…”

Section: Introductionmentioning

confidence: 99%

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Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Bao¹,

Kishnani²,

Wu³

et al. 1996

J. Clin. Invest.

155

110

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Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease resulting from deficient glycogen-branching enzyme (GBE) activity. The classic and most common form is progressive liver cirrhosis and failure leading to either liver transplantation or death by 5 yr of age. However, the liver disease is not always progressive. In addition, a neuromuscular type of the disease has been reported. The molecular basis of GSD-IV is not known, nor is there a known reason for the clinical variability. We studied the GBE gene in patients with various presentations of GSD-IV. Three point mutations in the GBE gene were found in two patients with the classical presentation: R515C, F257L, and R524X. Transient expression experiments showed that these mutations inactivated GBE activity. Two point mutations, L224P and Y329S, were detected in two separate alleles of a patient with the nonprogressive hepatic form. The L224P resulted in complete loss of GBE activity, whereas the Y329S resulted in loss of ‫ف‬ 50% of GBE activity. The Y329S allele was also detected in another patient with the nonprogressive form of GSD-IV but not in 35 unrelated controls or in patients with the more severe forms of GSD-IV. A 210-bp deletion from nucleotide 873 to 1082 of the GBE cDNA was detected in a patient with the fatal neonatal neuromuscular presentation. This deletion, representing the loss of one full exon, was caused by a 3 Ј acceptor splicing site mutation ( ag to aa ). The deletion abolished GBE activity. Our studies indicate that the three different forms of GSD-IV were caused by mutations in the same GBE gene. The data also suggest that the significant retention of GBE activity in the Y329S allele may be a reason for the mild disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Bao¹,

Kishnani²,

Wu³

et al. 1996

J. Clin. Invest.

155

110

View full text Add to dashboard Cite

show abstract

“…Patients with APBD usually present between the fourth and the sixth decade of life with a variable combination of symptoms and signs commonly including corticospinal involvement, peripheral neuropathy, bladder dysfunction, and, in about half of the patients, cognitive impairment. 10,21,23,33 A few magnetic resonance imaging (MRI) studies have shown nonspecific, leukodystrophy-like changes in cerebral white matter (WM), along with brain and spinal cord atrophy. 5,22,23,33 Most cases are apparently sporadic but a few familial clusterings involving siblings have been reported.…”

Section: Accepted 17 September 2007mentioning

confidence: 99%

Adult polyglucosan body disease: Proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene

et al. 2008

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Adult polyglucosan body disease (APBD) is characterized by the accumulation of insoluble glucose polymers within the central and peripheral nervous systems. A common missense mutation in the glycogen branching enzyme (GBE1) gene has been identified in Ashkenazi patients with APBD. We report on a non-Jewish patient with APBD on whom we performed proton magnetic resonance spectroscopic imaging of the brain. GBE activity in fibroblasts was markedly reduced, and a novel heterozygous mutation was identified in the GBE1 gene. Our findings widen the spectrum of APBD genotypes, underline the importance of performing GBE analysis in all APBD patients, and suggest that brain white matter degeneration in APBD may result from tissue damage involving axons and myelin.

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“…Outro exemplo de pesquisa bioquímica semelhante foi a descrição ,em dois pacientes com a doença de inclusão de polissacarídeos do adulto, de redução da atividade enzimática ramificante em polimorfonucleares 13 .…”

Section: Conclusãounclassified

Doença de Lafora: Uma possibilidade diagnóstica das demências juvenis

Dias‐Tosta¹,

Vieira²,

Alves³

et al. 1995

Arq. Neuro-Psiquiatr.

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RESUMO -Cinco casos de doença de Lafora são relatados, dando-se ênfase à sequência de eventos clínicos que permitiram a suspeita do diagnóstico e o posterior método de comprovação através de exames histopatológicos da pele e fígado. Todos os pacientes iniciaram o quadro clínico com diminuição do rendimento escolar ou distúrbio de memória, a que se seguiram crises convulsivas e mioclonias. Ressalta-se o caráter familiar da doença, a idade de início entre os 12 e 16 anos e a impossibilidade de se atingir um controle adequado das crises, mesmo se utilizando múltiplos esquemas terapêuticos. São discutidos os diagnósticos diferenciais do ponto de vista clínico e laboratorial mostrando que casos que se apresentem com esta evolução devem ser submetidos inicialmente a biópsia de pele e, se não se lograr a caracterização dos corpos de Lafora nas glândulas sudoríparas, proceder-se-á ao exame do fígado, que foi positivo em quatro das cinco biópsias.PALAVRAS-CHAVE: demência juvenil, epilepsia mioclônica, corpos de Lafora, biópsia de pele, biópsia de fígado. Lafora's disease: a possible diagnosis of juvenile dementiaSUMMARY -Five patients aged 12 to 16 years old were admitted between 1987 and 1994 at the neurological unit because of uncontrolled epilepsy. They had had a normal development until the adolescence, when a history of poor school performance and memory difficulty started. It is emphasized the clinical sequence of dementia followed by tonic-clonic seizures and myoclonus, the positive family history and the difficult therapeutic management, in spite of multiple anticonvulsant combinations, including sodium valproate and clonazepam. The clinical and laboratory differential diagnosis were discussed to show that similar cases should be submitted to skin biopsy looking for Lafora bodies in apocrine and eccrine glands. However, the liver is considered as the most reliable site for the biopsy, which in our study showed positivity in four out of the five cases.KEY WORDS: juvenile dementia, seizures, myoclonus, Lafora bodies, skin biopsy, liver biopsy.As epilepsias mioclônicas progressivas (EMP) constituem um desafio diagnóstico para o neurologista clínico, seja pela sua raridade, seja pelo grupo etário acometido, entre 6 e 19 anos 2 -517 , ou pela necessidade do aconselhamento genético em virtude de seu caráter familiar e da gravidade do prognóstico. As EMP foram definidas em Marseille (1990) como um subgrupo dentro das epilepsias generalizadas, caracterizadas por crises convulsivas generalizadas, mioclonias e deterioração neurológica progressiva, principalmente demência e ataxia 14 . A descrição dos corpos de Lafora em 1911, permitiu a separação desta entidade nosológica de outras hereditárias como UnverrichtLundborg, de doenças metabólicas como as sialidoses, lipofuscinose-ceróide, Gaucher, citopatias

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Hereditary branching enzyme dysfunction in adult polyglucosan body disease: A possible metabolic cause in two patients

Cited by 81 publications

References 32 publications

Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Adult polyglucosan body disease: Proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene

Doença de Lafora: Uma possibilidade diagnóstica das demências juvenis

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