Primary creatine deficiency syndrome as a potential missed diagnosis in children with psychomotor delay and seizure: case presentation with two novel variants and literature review

Rostami, Parastoo; Hosseinpour, Sareh; Ashrafi, Mahmoud Reza; Alizadeh, Hussain; Garshasbi, Masoud; Tavasoli, Ali Reza

doi:10.1007/s13760-019-01168-6

Cited by 15 publications

(12 citation statements)

References 20 publications

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“…Since the first report in 1994, ~130 cases of GAMT deficiency have been reported worldwide [ 18 , 22 , 25 , 26 ]. These cases highlight the non-specific nature and heterogeneity of the clinical manifestations with variable age of onset and severity of different features.…”

Section: Discussionmentioning

confidence: 99%

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Adult GAMT deficiency: A literature review and report of two siblings

Modi

Khan

Lee

et al. 2021

Molecular Genetics and Metabolism Reports

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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.

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Section: Discussionmentioning

confidence: 99%

“…At the time of discovery, the variant was novel (i.e. never reported before) but since then a case report of exome sequencing in a 30-month-old boy with persistent motor and speech delay identified the same c.134G > A; p.Trp45* variant [ 25 ]. These are the first and only two adult cases with this variant.…”

Section: Discussionmentioning

confidence: 99%

Adult GAMT deficiency: A literature review and report of two siblings

Modi

Khan

Lee

et al. 2021

Molecular Genetics and Metabolism Reports

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“…Low urinary creatinine excretion, reflecting a low body creatine pool, and accumulation of guanidinoacetate-the substrate of the deficient enzyme activity-were characteristic biochemical findings [11]. Approximately 130 patients with GAMT-D have been reported in literature, either as individual case reports or as small case series with an incidence of 1:550,000-1:2,640,000 [12][13][14][15].…”

Section: Gamt-d Syndrome: Clinical and Biochemical Profilingmentioning

confidence: 99%

“…Intellectual disability-the clinical hallmark of GAMT deficiency-is present in all affected patients, and is moderate or severe in most patients (60-90%) [7,17,21]. Less frequently, developmental arrest and regression is reported [12,17,22].…”

Section: Gamt-d Syndrome: Clinical and Biochemical Profilingmentioning

confidence: 99%

Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

Rossi

Nardecchia

Pierigé

et al. 2021

Genes

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Guanidinoacetate methyltransferase deficiency (GAMT-D) is one of three cerebral creatine (Cr) deficiency syndromes due to pathogenic variants in the GAMT gene (19p13.3). GAMT-D is characterized by the accumulation of guanidinoacetic acid (GAA) and the depletion of Cr, which result in severe global developmental delay (and intellectual disability), movement disorder, and epilepsy. The GAMT knockout (KO) mouse model presents biochemical alterations in bodily fluids, the brain, and muscles, including increased GAA and decreased Cr and creatinine (Crn) levels, which are similar to those observed in humans. At the behavioral level, only limited and mild alterations have been reported, with a large part of analyzed behaviors being unaffected in GAMT KO as compared with wild-type mice. At the cerebral level, decreased Cr and Crn and increased GAA and other guanidine compound levels have been observed. Nevertheless, the effects of Cr deficiency and GAA accumulation on many neurochemical, morphological, and molecular processes have not yet been explored. In this review, we summarize data regarding behavioral and cerebral GAMT KO phenotypes, and focus on uncharted behavioral alterations that are comparable with the clinical symptoms reported in GAMT-D patients, including intellectual disability, poor speech, and autistic-like behaviors, as well as unexplored Cr-induced cerebral alterations.

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“…Treatment with oral creatine monohydrate (dosage of 100-200 mg/kg in 3 doses) and a special diet can result in improvements in seizures and intellectual improvements (Table 1). 14,15 In GLUT-1 deficiency, SLC2A1 gene mutations lead to a defect in glucose transport to brain cells and low CSF glucose. The clinical spectrum of GLUT-1 deficiency ranges from movement disorders to developmental delay, microcephaly and intractable epilepsy.…”

mentioning

confidence: 99%

Treating epilepsy with options other than antiepileptic medications

Muthaffar

2020

NSJ

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Primary creatine deficiency syndrome as a potential missed diagnosis in children with psychomotor delay and seizure: case presentation with two novel variants and literature review

Cited by 15 publications

References 20 publications

Adult GAMT deficiency: A literature review and report of two siblings

Adult GAMT deficiency: A literature review and report of two siblings

Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

Treating epilepsy with options other than antiepileptic medications

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