Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait. Exome sequencing identified a homozygous nonsense variant in GAMT: NM_000156.5:c.134G>A (p.Trp45*). We also performed a literature review and compiled the genetic and clinical characteristics of all adult cases of GAMT deficiency reported to date. When compared to the adult cases previously reported, the musculoskeletal phenotype and the rapidly progressive nature of neurological and motor decline seen in our patients is striking. This study presents an opportunity to gain insights into the adult presentation of GAMT deficiency and highlights the need for in-depth evaluation and reporting of clinical features to expand our understanding of the phenotypic spectrum.

胍基乙酸甲酯甲基转移酶（GAMT）缺乏症是一种肌酸缺乏症，是先天性代谢错误，伴有进行性智力和神经功能恶化。由于大多数病例是在儿童早期就被发现和治疗的，因此有助于理解疾病自然史的成人表型很少见。我们描述了巴基斯坦的一个近亲家庭中的两名GAMT缺乏成人病例，这些病例具有全球发育迟缓，认知障碍，过度流口水，行为异常，挛缩和明显的骨畸形的历史，最初被认为是步态异常的原因。外显子测序中标识出来的纯合废话变种GAMT：NM_000156.5：c.134G> A（p.Trp45 *）。我们还进行了文献综述，并汇编了迄今报告的所有GAMT缺乏成人病例的遗传和临床特征。与先前报道的成年病例相比，在我们的患者中看到的肌肉骨骼表型以及神经系统和运动功能下降的迅速进展性令人震惊。这项研究为深入了解成人GAMT缺乏症提供了机会，并强调需要深入评估和报告临床特征以扩大我们对表型谱的了解。