背景技术先天性糖基化障碍(CDG)是由聚糖合成或加工缺陷引起的一组代谢疾病。亚组的数量及其表型谱继续扩大,与N-糖基化缺陷最相关。ALG9-CDG(以前为CDG-IL)是ALG9中突变的结果。该基因编码α-1,2-甘露糖基转移酶。迄今为止,据报道,共有来自6个不同家庭的10例患者出现4个ALG9突变之一.这些患者中有7名具有类似的表型,未能茁壮成长,变形特征,癫痫发作,肝和/或肾囊肿;其他三名患者死于子宫内致命的骨骼发育不良。该报告描述了另一位患有ALG9-CDG的患者,其表型较轻。这个病人是白种人出生的女性,加拿大,苏格兰体面的非近亲父母。婚前,变形特征,检测到大量肾囊肿和轻微的心脏畸形。出生后,变形特征包括浅轨道,小颌畸形,发育不良的乳头,马蹄足,脂肪营养不良和角质病。她无法茁壮成长和癫痫发作。代谢检查包括转铁蛋白等电聚焦分析,显示了1型模式。这通过聚糖分析得到了证实,在ALG9中鉴定出纯合突变,c.860A>G(p。Tyr287Cys)(NM_1234567890)。先前已在两名加拿大患者中作为致病性突变发表。我们的目标是通过描述表型谱并提供对预后的进一步见解,为这种疾病的知识不断增长做出贡献。
Congenital disorders of glycosylation (CDG) are a group of metabolic diseases resulting from defects in glycan synthesis or processing. The number of subgroups and their phenotypic spectrums continue to expand with most related to deficiencies of N-glycosylation.
ALG9-CDG (previously CDG-IL) is the result of a mutation in
ALG9. This gene encodes the enzyme alpha-1,2-mannosyltransferase. To date, a total of 10 patients from 6 different families have been reported with one of four
ALG9 mutations. Seven of these patients had a similar phenotype with failure to thrive, dysmorphic features, seizures, hepatic and/or renal cysts; the other three patients died in utero from a lethal skeletal dysplasia. This report describes an additional patient with
ALG9-CDG who has a milder phenotype. This patient is a term female born to Caucasian, Canadian, non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. The metabolic work-up included analysis of a transferrin isoelectric focusing, which showed a type 1 pattern. This was confirmed by glycan profiling, which identified ahomozygous mutation in
ALG9, c.860A > G (p.Tyr287Cys) (NM_1234567890). This had been previously published as a pathogenic mutation in two Canadian patients. Our goal is to contribute to the growing body of knowledge for this disorder by describing the phenotypic spectrum and providing further insight on prognosis.