Menkovic Iskren, Williams Monika, Makhijani Neelam, Wei Ruhan, Young Sarah P, El-Gharbawy Areeg, Stiles Ashlee R
Biochemical Genetics Laboratory, Duke University Health System, Durham, NC, USA.
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Mol Genet Metab Rep. 2025 Jan 20;42:101191. doi: 10.1016/j.ymgmr.2025.101191. eCollection 2025 Mar.
-related disorders are autosomal recessive lysosomal diseases caused by enzymatic deficiency of β-galactosidase. Enzymatic deficiency of β-galactosidase may lead to one of two phenotypes, GM1 gangliosidosis or mucopolysaccharidosis IVB (MPS IVB). GM1 gangliosidosis is a neurodegenerative disorder with variable skeletal disease and involvement of other systems. The age of onset correlates with the extent of neurological involvement and established genotype/phenotype correlations. Mucopolysaccharidosis IVB is characterized by a skeletal dysplasia without neurological involvement. Diagnostic work-up for related disorders includes enzyme analysis, biomarker analysis, molecular testing, and laboratory imaging studies. We report a patient who presented with persistent elevations of alkaline phosphatase (ALP) and subtle dysmorphic facial features. An initial skeletal survey at birth was unrevealing; however, a repeat at 3 months of age was abnormal with anterior beaking of the lumbar vertebrae and hemivertebrae of the lower cervical spine. Urinary glycosaminoglycan (GAG) analysis revealed a marked elevation of keratan sulfate (KS). Clinical exome sequencing revealed pathogenic heterozygous variants in , consistent with -related GM1 gangliosidosis. Our case demonstrates that persistent elevations of ALP may be an early indicator for GM1 gangliosidosis in an infant with progressive multisystem disease, indicating the need for early genetic consultation. This case also highlights the utility of repeat skeletal surveys with abnormalities detected at 3 months of age.
相关疾病是由β-半乳糖苷酶酶缺乏引起的常染色体隐性溶酶体疾病。β-半乳糖苷酶酶缺乏可能导致两种表型之一，即GM1神经节苷脂贮积症或IVB型黏多糖贮积症（MPS IVB）。GM1神经节苷脂贮积症是一种神经退行性疾病，伴有可变的骨骼疾病和其他系统受累。发病年龄与神经受累程度以及已确定的基因型/表型相关性有关。IVB型黏多糖贮积症的特征是骨骼发育异常但无神经受累。相关疾病的诊断检查包括酶分析、生物标志物分析、分子检测和实验室影像学研究。我们报告了一名患者，其碱性磷酸酶（ALP）持续升高且面部有细微畸形特征。出生时的首次骨骼检查未发现异常；然而，3个月大时复查异常，腰椎椎体前缘呈喙状，下颈椎半椎体畸形。尿糖胺聚糖（GAG）分析显示硫酸角质素（KS）显著升高。临床外显子组测序显示致病杂合变异，与相关的GM1神经节苷脂贮积症一致。我们的病例表明，对于患有进行性多系统疾病的婴儿，ALP持续升高可能是GM1神经节苷脂贮积症的早期指标，这表明需要早期进行遗传咨询。该病例还强调了3个月大时检测到异常后重复进行骨骼检查的作用。
