疾患詳細

疾患詳細





#230650
GM1-gangliosidosis, type III
(Gangliosidosis, generalized GM1, adult type)
(Gangliosidosis, generalized GM1, chronic type)
(Gangliosidosis, generalized GM1, type III)
(Gangliosidosis, generalized GM1, type 3)

ガングリオシドーシス III 型
(ガングリオシドーシス, 全身性 GM1, 成人型)
(ガングリオシドーシス, 全身性 GM1, 慢性型)
(ガングリオシドーシス, 全身性 GM1, 3型)
指定難病19 ライソゾーム病
小児慢性特定疾病 代86 GM1-ガングリオシドーシス

責任遺伝子:611458 Galactosidase, beta-1 (GLB1) <3p21.33>
遺伝形式:常染色体劣性

(症状)
(GARD)
 
 Abnormality of blood and blood-forming tissues (血液および造血組織の異常) [HP:0001871] [22]
 Abnormality of the face (顔異常) [HP:0000271] [04]
 Anterior beaking of lumbar vertebrae  0008430
 Autosomal recessive inheritance (常染色体劣性遺伝) [HP:0000007]
 Decreased beta-galactosidase activity (beta-galactosidase 活性減少) [HP:0008166]
 Diffuse cerebral atrophy (びまん性大脳萎縮) [HP:0002506] [160121]
 Dystonia (ジストニア) [HP:0001332] [0240]
 Flared iliac wings (腸骨翼フレア) [HP:0002869] [1142]
 Foam cells (泡沫細胞) [HP:0003651]
 Hypoplastic acetabulae (寛骨臼低形成) [HP:0003274] [1143]
 Intellectual disability, mild (軽度知的障害) [HP:0001256] [0120]
 Kyphosis (後弯) [HP:0002808] [161500]
 Opacification of the corneal stroma (角膜間質混濁) [HP:0007759] [0620]
 Platyspondyly (扁平脊椎) [HP:0000926] [161505]
 Scoliosis (側弯) [HP:0002650] [161502]
 Short stature (低身長) [HP:0004322] [0130]
 Skeletal muscle atrophy (骨格筋萎縮) [HP:0003202] [0270]
 Slurred speech (不明瞭発語) [HP:0001350] [0230]

(UR-DBMS)
【一般】正常な早期発達
 精神遅滞, 軽度の
 けいれん (まれ)
 低身長
 肝腫なし
 脾腫なし
【神経】構音障害 (不正確な言語)
 *運動失調
 筋萎縮
 ミオクローヌスなし
 けいれんなし
 ジストニア
【顔】正常な顔貌
【眼】チェリーレッド斑なし
 角膜混濁
【体幹】内臓腫大なし
【骨盤】寛骨臼低形成
 平坦な大腿骨頭
 平坦な腸骨翼
【X線】軽度の扁平椎体
 軽度の腰椎前方突出
 後弯
 側弯
 大脳萎縮, 軽度びまん性
【皮膚】びまん性体部被角血管腫
【検査】beta-galactosidase 活性低下 (白血球, 線維芽細胞, 血漿)
【血液】泡沫細胞 (骨髄)
【その他】3-30 歳発症

(要約)
●GM1 gangliosidoses は, beta-galactosidase 欠乏が原因で, 中枢神経および末梢神経細胞の特に神経細胞に酸性脂質物質の異常な蓄積を生じる
 2つの型がある
 早期乳児型, 後期乳児型, 成人型
●早期乳児型 GM1 (最重症型で生後すぐ発症)
 神経変性, けいれん, 肝腫, 脾腫, 粗な顔貌, 骨格不規則性, 関節拘縮, 腹部膨満, 筋衰弱, 音への驚愕反射亢進, 歩行障害がみられる
 半数はチェリーレッド斑をもつ
 1歳までに聾と盲になりうる
 心合併症または肺炎で3歳までに死亡する
●後期乳児型 GM1
 1〜3歳発症
 運動失調, けいれん, 認知症, 発語困難など
●成人型 GM1
 3〜30歳発症
 筋萎縮, より軽度でより進行の遅い神経合併症, 数例での角膜混濁, ジストニアなど
 角化血管腫が体幹下部に生じうる
 肝脾腫はない

<小児慢性特定疾病 代86 GM1-ガングリオシドーシス>
概要・定義
β-ガラクトシドーシスは, 糖脂質の末端β-ガラクトース結合を加水分解する酵素であるβ-ガラクトシダーゼが欠損することにより発症する, 常染色体劣性遺伝形式を示す遺伝病である。脳をはじめとして全身臓器にGM1ガングリオシドなどの糖脂質, オリゴ糖, ムコ多糖(ケラタン硫酸)などが蓄積する。進行性の中枢神経障害を主とするGM1-ガングリオシドーシスと, 中枢神経障害を伴わない全身骨系統疾患であるモルキオB病に分類される。発症頻度は1/10万~20万人とされ, 発症時期と臨床経過により, 乳児型, 若年型, 成人型に分類される。乳児型は生後3~6ヶ月までに発達の遅れが見られ, 筋緊張低下, 音に対する過敏症, 全身性けいれん, 眼底のチェリーレッドスポット, 肝脾腫, 全身の骨異常を呈する。若年型は1歳前後から発症し, 臨床症状は乳児型に類似するが, やや軽度である。肝脾腫やチェリーレッドスポット, 骨異常はほとんどない。成人型は, 発達は正常で知能障害が少ない。歩行障害, 構音障害が初期症状として多く, ジストニアなどの錐体外路症状を呈する。
疫学
罹患率は10万~20万人に1人と考えられている。
病因
βガラクトシダーゼ酵素をコードするGLB1遺伝子の遺伝子変異で発症する。160を超える遺伝子変異が報告されており, 日本では, R201C遺伝子変異をもつ若年型の患者さんとI51T遺伝子変異をもつ成人型の患者さんが比較的多い。
βガラクトシダーゼ酵素の欠損により, GM1-ガングリオシドが細胞内に蓄積しており, この蓄積が2次的なコレステロールの蓄積や細胞内脂質輸送の異常を引き起こす。

症状
乳児型は, 生後6ヶ月までに発達の遅れがあり, 筋緊張低下, 音に対する過敏性が見られることもある。腱反射は更新し, 全身けいれんが出現する。眼底のチェリー・レットスポット, 肝脾腫, 全身の骨異常などが進行する。若年型は1歳前後から発症し, 症状は乳児型より軽度である。肝脾腫, チェリー・レットスポットなどは目立たない。成人型は, 知的障害は少なく, 初期には構音障害が目立つ。歩行障害, ジストニアなどの錘体外路症状が目立つ。
診断
末梢リンパ球または培養皮膚線維芽細胞のβガラクトシダーゼ酵素活性を測定し, 低下(10%以下)している場合に本症を診断できるが, ガラクトシアリドーシスでもβガラクトシダーゼ酵素活性が低下するので鑑別する必要がある。GLB1遺伝子診断も診断には有用である。
診断方法
1. 乳児型では, チェリーレッドスポットが診断の参考となる。成人型では, 初期症状として構音障害が比較的特徴となり, 骨変化も伴うことがある
2. モルキオB病は, 骨症状のみで尿中ケラタン硫酸の排出増加を認める。
3. 酵素活性測定と遺伝子診断を行って診断を確定する。
4. 酵素活性測定では, 末梢血リンパ球または培養皮膚線維芽細胞を用いてβ-ガラクトシダーゼ活性を測定する。β-ガラクトシダーゼ活性の低下はガラクトシアリドーシスでも認められるが, この疾患では同時にシアリダーゼも低下している。シアリダーゼは非常に不安定な酵素なので, 活性測定には注意を要する。
5. 遺伝カウンセリングや現在開発中のシャペロン療法などの情報として, 遺伝子診断は有用である。しかし, 酵素活性から診断が確実となった患者でも, 遺伝子診断では変異が見つからない場合がある。
当該事業における対象基準
全A  疾患名に該当する場合
治療
現段階では対症療法に限られる。基礎的にはシャペロン療法が開発されてきているが, 現在, 臨床応用されている治療法はない。
予後
乳児型では予後不良で, 3歳までに亡くなる患者さんが多い。若年型は, 10歳前後で寝たきりになる場合が多い。成人型はジストニアや構音障害が進行し, 生活に支障を来す。
成人期以降
成人型では錐体外路症状が目立ち, 脊髓小脳変性症などとの鑑別に注意を要する。

(Occurrence) 25 cases
(Comment) allelic to type I and MPS IVB
(責任遺伝子) *611458 Galactosidase, beta-1 (GLB1) <3p21.33>
(1) GM1-gangliosidosis, type I (230500)
.0001 GM1-gangliosidosis, type I [GLB1, ARG49CYS] (dbSNP:rs72555358) (RCV000672371...) (Nishimoto et al. 1991)
.0002 GM1-gangliosidosis, type I [GLB1, ARG457TER] (dbSNP:rs72555359) (ExAC:rs72555359) (RCV000667074...) (Nishimoto et al. 1991)
.0005 GM1-gangliosidosis, type I [GLB1, 165-BP DUP] (RCV000000975) (Yoshida et al. 1991)
.0006 GM1-gangliosidosis, type I [GLB1, GLY123ARG] (dbSNP:rs28934274) (RCV000196532...) (Yoshida et al. 1991)
.0007 GM1-gangliosidosis, type I [GLB1, TYR316CYS] (dbSNP:rs72555361) (RCV000000977...) (Yoshida et al. 1991)
.0012 GM1-gangliosidosis, type I [GLB1, 23-BP DUP [dbSNP:rs587776524] (RCV000000983) (Oshima et al. 1992)
.0014 GM1-gangliosidosis, type I [GLB1, IVS1DS, 1-BP INS, +3 [dbSNP:rs587776525] (RCV000000985...) (Morrone et al. 1994; Chakraborty et al. 1994)
.0017 GM1-gangliosidosis, type I [GLB1, ARG208CYS] (dbSNP:rs72555366) (RCV000633470...) (Boustany et al. 1993; Chiu et al. 1996)
.0019 GM1-gangliosidosis, type I, with cardiac involvement [GLB1, ARG351TER] (dbSNP:rs72555372) (ExAC:rs72555372) (RCV000000990...) (Hinek et al. 2000)
.0023 GM1-gangliosidosis, type I, with caradiac involvement (GM1-gangliosidosis, type I, included) [GLB1, ARG59HIS] (dbSNP:rs72555392) (RCV000059350...) (Morrone et al. 2000; Santamaria et al. 2007)
.0024 GM1-gangliosidosis, type I, with caradiac involvement [GLB1, IVS14AS, A-G, -2 [dbSNP:rs587776526] (RCV000000996) (Morrone et al. 2000)
.0025 GM1-gangliosidosis, type I, with caradiac involvement [GLB1, TYR591ASN] (dbSNP:rs72555373) (RCV000000997) (Morrone et al. 2000)
.0026 GM1-gangliosidosis, type I, with caradiac involvement [GLB1, TYR591CYS] (dbSNP:rs72555371) (RCV000673090...) (Morrone et al. 2000)
(2) GM1-gangliosidosis, type II (230600)
.0003 GM1-gangliosidosis, type II [GLB1, ARG201CYS] (dbSNP:rs72555360) (RCV000411359...) (Nishimoto et al. 1991; Yoshida et al. 1991; Caciotti et al. 2003)
.0022 GM1-gangliosidosis, type II [GLB1, ARG68TRP [dbSNP:rs72555370] (RCV000000993...) (Caciotti et al. 2003)
(3) GM1-gangliosidosis, type III (230650)
.0004 GM1-gangliosidosis, type III [GLB1, ILE51THR] (dbSNP:rs72555390) (RCV000671053...) (Nishimoto et al. 1991; Yoshida et al.1991; Yoshida et al. 1992)
.0008 GM1-gangliosidosis, type III [GLB1, ARG457GLN] (dbSNP:rs28934886) (RCV000000978) (Yoshida et al. 1991)
.0013 GM1-gangliosidosis, type III [GLB1, THR82MET] [dbSNP:rs72555393] (RCV000624609...) (Chakraborty et al. 1994)
(4) Mucopolysaccharidosis type IVB (253010)
.0009 Mucopolysaccharidosis type IVB [GLB1, TRP273LEU] (dbSNP:rs72555362) (RCV000000979) (Oshima et al. 1991; Paschke et al. 2001)
.0010 Mucopolysaccharidosis type IVB (GM1-gangliosidosis, type I, included) [GLB1, ARG482HIS] (dbSNP:rs72555391) (ExAC:rs72555391) (RCV000174680...) (Oshima et al. 1991; Mosna et al. 1992; Suzuki and Oshima 1993)
.0011 Mucopolysaccharidosis type IVB [GLB1, TRP509CYS] (dbSNP:rs72555363) (RCV000000982) (Oshima et al. 1991)
.0015 Mucopolysaccharidosis type IVB [GLB1, TYR83HIS] (dbSNP:rs72555364) (RCV000000986) (Ishii et al. 1995)
.0016 Mucopolysaccharidosis type IVB [GLB1, ARFG482CYS] (dbSNP:rs72555365) (RCV000119100...) (Ishii et al. 1995)
.0018 Mucopolysaccharidosis type IVB [GLB1, GLY438GLU] (dbSNP:rs72555367) (RCV000000989) (Hinek et al. 2000)
.0020 Mucopolysaccharidosis type IVB [GLB1, THR500ALA] (dbSNP:rs72555368) (RCV000000991...) (Paschke et al. 2001)
.0021 Mucopolysaccharidosis type IVB [GLB1, GLN408PRO] (dbSNP:rs72555369) (RCV000667601...) (Paschke et al. 2001)

*GLB1: Galactosidase, beta-1 (677 amino acids)
・GLB1 遺伝子は beta-galactosidase-1 (EC 3.2.1.23)をコードする
・beta-galactosidase-1 はリソソーム酵素で, ganglioside 基質と他の glycoconjugates から末端βガラクトースを加水分解する
 beta-galactosidase は, 細胞表面受容体の成分である neuraminidase (NEU1; 608272) と protective protein/cathepsin A (PPCA; 256540)複合でも生じる

(Note)
A number sign (#) is used with this entry because type III GM1-gangliosidosis is caused by mutation in the gene encoding beta-galactosidase-1 (GLB1; 611458).

For a general discussion of classification and phenotypic heterogeneity of GM1-gangliosidosis, see type I (230500).

GM1-gangliosidosis type III is an autosomal recessive lysosomal storage disorder characterized by neurodegeneration and mild skeletal changes. Age at onset ranges from 3 to 30 years. The disorder is less severe than GM1-gangliosidosis types I and II (230600). Type III shows extreme clinical variability, with some patients having only focal neurologic signs, such as dystonia, and others having more severe involvement with extrapyramidal signs and mental retardation. GLB1 enzymatic activity usually ranges from approximately 4 to 10% of control values (Suzuki et al., 2001).

Clinical Features
Wenger et al. (1974) described beta-galactosidase deficiency in young adults.

Loonen et al. (1974) reported a patient with type III GM1-gangliosidosis who had angiokeratoma beginning at age 8 years, cerebellar dysfunction and diminishing vision beginning at age 16, and myoclonic fits, intellectual deterioration and coarsening of the face beginning at age 22.

Suzuki et al. (1977) reported 2 Japanese sibs, aged 34 and 30 years, respectively, with the adult form of GM1-gangliosidosis. They had progressive pyramidal and extrapyramidal disease with generalized muscle atrophy without dysmorphism or macular cherry-red spots. Suzuki et al. (1978) found increased GM1 accumulation in cultured skin fibroblasts from these patients. However, the accumulation was less than that observed in patients with type I infantile disease, indicating a correlation of storage material with disease severity. By cell complementation studies, Suzuki et al. (1979) confirmed that the Japanese adults had a variant form of beta-galactosidase deficiency.

Stevenson et al. (1978) reported 3 patients from 2 families with type III GM1-gangliosidosis. All had onset by age 4 years, but showed survival into adulthood. One affected boy had early signs of stuttering, overactivity, mental retardation, spasticity, and ataxia. Radiographic examination at age 19 years showed scoliosis, irregularity of the vertebral plates, flattened vertebral bodies, and dysplastic femoral heads. Another child developed walking difficulties at age 3 and showed progressive deterioration with loss of speech and the development of choreic movements and progressive spasticity. The third patient began deteriorating at age 3 years. He never learned to speak clearly, developed abnormal hand movements, and showed mental retardation. He had generalized spasticity, athetoid movements, and rigidity. None of the patients had visceromegaly or macular red spots. Stevenson et al. (1978) stated that these patients had a more severe phenotype than usually seen in type III, but less severe than in types I and II.

Wenger et al. (1980) described a brother and sister, aged 19 and 25 years, respectively, with ataxia, mild intellectual deterioration, slurred speech, mild vertebral changes and little, if any, visceromegaly. A primary defect in beta-galactosidase was indicated by the half-normal values in many relatives, including both parents, and by the normal levels of sialidase. Complementation with infantile type I GM1-gangliosidosis did not occur, indicating that it was a variant form of that disorder. Chakraborty et al. (1994) provided follow-up of the family reported by Wenger et al. (1980). The 38-year-old sister and 32-year-old brother had normal childhood development but delayed or defective speech development. Neurologic workup of the sister at age 19 showed a defect in articulation and impairment of upper and lower limb coordination. At age 38, she showed a severe and progressive stutter, hyperactive deep tendon reflexes, especially in the legs, and pes cavus. Intelligence, cranial nerve function, and funduscopic examination were all normal. Bilateral total hip replacement had been required at the age of 33 years. The brother showed progressive dysarthria, moderate ataxia, and intention tremor, but cranial nerve funduscopic examinations were normal. Flattening of vertebral bodies, progressive kyphosis, and subluxation of the right hip were features. Both sides of the family originated from a small town in western Denmark.

Goldman et al. (1981) and Kobayashi and Suzuki (1981) reported a 27-year-old man with GM1-gangliosidosis who experienced a slowly progressive dystonia that began at about age 4 years. Dystonia primarily affected the face and limbs and eventually became incapacitating. Myoclonus, seizures, and macular cherry-red spots were never observed. Postmortem examination revealed intraneuronal storage, localized predominantly to the basal ganglia, in which neurons contained round, multilamellated inclusions. Other areas of the central nervous system appeared relatively unaffected, although small basilar dilatations were observed in scattered cortical pyramidal neurons and Purkinje cell dendrites showed focal swellings. Vacuolated cells of the reticuloendothelial system were observed, including Kupffer cells and histiocytes in the spleen, marrow, and intestinal tract. Biochemical analysis revealed a generalized beta-galactosidase deficiency with specific accumulation of GM1 ganglioside in the basal ganglia.

Uyama et al. (1992) described 3 Japanese brothers with type III GM1-gangliosidosis presenting as dystonia. The patients were examined at ages 28, 31, and 33 years. They had developed dysarthria with facial grimacing in early childhood. As adults, all had generalized dystonia that did not disappear when the patients were lying or sitting relaxed. Brain imaging showed bilaterally symmetric high density lesions only in the putamen.

Yoshida et al. (1992) reported 16 Japanese patients with adult GM1-gangliosidosis from 10 unrelated families. Age at onset ranged from 3 to 30 years. The main clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic posturing, facial grimacing, and parkinsonism were commonly seen. Dysmorphism, visceromegaly, and severe mental impairment were not observed.

Chakraborty et al. (1994) reported a 21-year-old patient with type III GM1-gangliosidosis who presented at age 3 years with speech difficulties that continued as a severe stutter. Neurologic examination demonstrated spastic quadriparesis, especially in the legs, with a scissoring gait. The patient had a history of urinary incontinence. Cranial nerve and funduscopic examinations, as well as intellect, were normal. Magnetic resonance imaging showed mild ventricular enlargement. The patient was also described as having short stature and scoliosis.

Biochemical Features
Early complementation studies on cells from patients with types I, II, and III GM1-gangliosidosis yielded conflicting results. Although mutant beta-galactosidase-1 in the different types is due to allelic mutations at the same locus, some studies showed complementation between the different types (see, e.g. Galjaard et al. (1975, 1975) and Koster et al., 1976; Reuser et al., 1979). However, in a detailed review, O'Brien and Norden (1977) discussed several possible explanations for the finding of complementation between different types of GM1-gangliosidosis, including alterations of tertiary structure and protein-protein interaction between different mutant monomers. O'Brien and Norden (1977) argued that the findings of complementation did not necessarily imply that the different types of GM1-gangliosidosis were nonallelic.

Taylor et al. (1980) reported biochemical studies of 2 of the patients reported by Stevenson et al. (1978). Beta-galactosidase differed in pH optima, heat denaturation, NaCl kinetics, and electrophoretic mobility from each other and from the normal. No complementation was found in cell fusion studies. The authors concluded that the 2 patients had different primary mutations at the beta-galactosidase locus that were likely structural in nature.

Mutoh et al. (1988) demonstrated altered properties of the mutant enzyme and altered apparent molecular weights of the enzyme isolated from the liver of a patient with the adult form of GM1-gangliosidosis. The findings suggested that some patients with the adult form have a structurally altered enzyme.

Hoogeveen et al. (1986) showed that the mutations in some cases of infantile and adult forms of GM1-gangliosidosis interfere with the phosphorylation of precursor beta-galactosidase. As a result, the precursor is secreted instead of being compartmentalized into the lysosomes and further processed.

Molecular Genetics
In the affected sibs reported by Wenger et al. (1980}), Chakraborty et al. (1994) identified compound heterozygosity for 2 mutations in the GLB1 gene (611458.0013; 611458.0022).

In 6 Japanese patients with the adult/chronic form of GM1-gangliosidosis, Nishimoto et al. (1991) identified a mutation in the GLB1 gene (I51T; 611458.0004).

Yoshida et al. (1991, 1992) also found the I51T mutation in Japanese patients with adult GM1-gangliosidosis. All patients except 1 were homozygotes. One patient was a compound heterozygote with an R457Q mutation (611458.0008). Clinically, the compound heterozygous patient showed more severe neurologic manifestations and a more rapid clinical course than did the homozygotes. The I51T allele showed 5.28 to 7.28% residual enzyme activity, whereas the compound heterozygous patient had 4.24% residual activity. The mutations causing residual enzyme activity appeared to be related to severity of clinical manifestations, but other genetic or environmental factors likely also contributed to the phenotype since there was considerable variation in age of onset and clinical course among I51T homozygotes.

(文献)
(1) Loonen, M. C. B.; van de Lugt, L.; Franke, C. L. : Angiokeratoma corporis diffusum and lysosomal enzyme deficiency. (Letter) Lancet 2: 785 only, 1974)
(2) Wenger, D. A.; Goodman, S. I.; Myers, G. B. : Beta-galactosidase deficiency in young adults. (Letter) Lancet 2: 1319-1320, 1974)
(3) Yamamoto, A.; Adachi, S.; Kawamura, S.; Takahashi, M.; Kitani, T.; Ohtori, T.; Shinji, Y.; Nishikawa, M. : Localized beta-galactosidase deficiency. Occurrence in cerebellar ataxia with myoclonus epilepsy and macular cherry-red spot--a new variant of Gm(1)-gangliosidosis. Arch. Intern. Med. 134: 627-634, 1974)
(4) Galjaard, H.; Hoogeveen, A.; Keijzer, W.; DeWit-Verbeek, H. A.; Reuser, A. J. J. : Different gene mutations in variants of Gm(1)- and Gm(2)-gangliosidosis demonstrated by enzyme analysis of (single) somatic hybrid cells. Birth Defects Orig. Art. Ser. XI(3): 150-156, 1975) (Note: Alternate: Cytogenet. Cell Genet. 14: 320-326, 1975)
(5) Galjaard, H.; Hoogeveen, A.; Keijzer, W.; deWit-Verbeek, H. A.; Reuser, A. J. J.; Ho, M. W.; Robinson, D. : Genetic heterogeneity in GM1-gangliosidosis. Nature 257: 60-62, 1975)
(6) Koster, J. F.; Niermeijer, M. F.; Loonen, M. C. B.; Galjaard, H. : Beta-galactosidase deficiency in an adult: a biochemical and somatic cell genetic study on a variant of GM-1-gangliosidosis. Clin. Genet. 9: 427-432, 1976)
(7) O'Brien, J. S.; Norden, A. G. W. : Nature of the mutation in adult beta-galactosidase deficient patients. Am. J. Hum. Genet. 29: 184-190, 1977)
(8) Suzuki, Y.; Nakamura, N.; Fukuoka, K.; Shimada, Y.; Uono, M. : Beta-galactosidase deficiency in juvenile and adult patients: report of six Japanese cases and review of literature. Hum. Genet. 36: 219-229, 1977)
(9) Stevenson, R. E.; Taylor, H. A., Jr.; Parks, S. E. : Beta-galactosidase deficiency: prolonged survival in three patients following early central nervous system deterioration. Clin. Genet. 13: 305-313, 1978)
(10) Suzuki, Y.; Nakamura, N.; Fukuoka, K. : GM1-gangliosidosis: accumulation of ganglioside GM1 in cultured skin fibroblasts and correlation with clinical types. Hum. Genet. 43: 127-131, 1978)
(11) Reuser, A. J. J.; Andria, G.; de Wit-Verbeek, E.; Hoogeveen, A.; del Giudice, E.; Halley, D. : A two-year-old patient with an atypical expression of Gm(1)-beta-galactosidase deficiency: biochemical, immunological, and cell genetic studies. Hum. Genet. 46: 11-19, 1979)
(12) Suzuki, Y.; Furukawa, T.; Hoogeveen, A.; Verheijen, F.; Galjaard, H. : Adult type GM1-gangliosidosis: a complementation study on somatic cell hybrids. Brain Dev. 1: 83-86, 1979)
(13) Taylor, H. A.; Stevenson, R. E.; Parks, S. E. : Beta-galactosidase deficiency: studies of two patients with prolonged survival. Am. J. Med. Genet. 5: 235-245, 1980)
(14) Wenger, D. A.; Sattler, M.; Mueller, O. T.; Myers, G. G.; Schneiman, R. S.; Nixon, G. W. : Adult GM1 gangliosidosis: clinical and biochemical studies on two patients and comparison to other patients called variant or adult GM1 gangliosidosis. Clin. Genet. 17: 323-334, 1980)
(15) Goldman, J. E.; Katz, D.; Rapin, I.; Purpura, D. P.; Suzuki, K. : Chronic Gm(1) gangliosidosis presenting as dystonia: I. Clinical and pathological features. Ann. Neurol. 9: 465-475, 1981)
(16) Kobayashi, T.; Suzuki, K. : Chronic Gm(1) gangliosidosis presenting as dystonia: II. Biochemical studies. Ann. Neurol. 9: 476-483, 1981)
(17) Hoogeveen, A. T.; Reuser, A. J. J.; Kroos, M.; Galjaard, H. : GM1-gangliosidosis: defective recognition site on beta-galactosidase precursor. J. Biol. Chem. 261: 5702-5704, 1986
(18) Mutoh, T.; Naoi, M.; Nagatsu, T.; Takahashi, A.; Matsuoka, Y.; Hashizume, Y.; Fujiki, N. : Purification and characterization of human liver beta-galactosidase from a patient with the adult form of G(M1) gangliosidosis and a normal control. Biochim. Biophys. Acta 964: 244-253, 1988
(19) Nishimoto, J.; Nanba, E.; Inui, K.; Okada, S.; Suzuki, K. : GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. Am. J. Hum. Genet. 49: 566-574, 1991
(20) Yoshida, K.; Oshima, A.; Shimmoto, M.; Fukuhara, Y.; Sakuraba, H.; Yanagisawa, N.; Suzuki, Y. : Human beta-galactosidase gene mutations in G(M1)-gangliosidosis: a common mutation among Japanese adult/chronic cases. Am. J. Hum. Genet. 49: 435-442, 1991
(21) Uyama, E.; Terasaki, T.; Watanabe, S.; Naito, M.; Owada, M.; Araki, S.; Ando, M. : Type 3 GM1 gangliosidosis: characteristic MRI findings correlated with dystonia. Acta Neurol. Scand. 86: 609-615, 1992
(22) Yoshida, K.; Oshima, A.; Sakuraba, H.; Nakano, T.; Yanagisawa, N.; Inui, K.; Okada, S.; Uyama, E.; Namba, R.; Kondo, K.; Iwasaki, S.; Takamiya, K.; Suzuki, Y. : GM1 Gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients. Ann. Neurol. 31: 328-332, 1992
(23) Alroy, J.; Orgad, U.; Ucci, A. A.; Schelling, S. H.; Schunk, K. 8. Chakraborty, S.; Rafi, M. A.; Wenger, D. A. : Mutations in the lysosomal beta-galactosidase gene that cause the adult form of GM1 gangliosidosis. Am. J. Hum. Genet. 54: 1004-1013, 1994
(24) Chakraborty, S.; Rafi, M. A.; Wenger, D. A. : Mutations in the lysosomal beta-galactosidase gene that cause the adult form of GM1 gangliosidosis. Am. J. Hum. Genet. 54: 1004-1013, 1994
(25) Suzuki, Y.; Oshima, A.; Nanba, E. : Beta-galactosidase deficiency (beta-galactosidosis): GM1 gangliosidosis and Morquio B disease.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. II. New York: McGraw-Hill (8th ed.) Pp. 3775-3809, 2001

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