Mental retardation: a common clinical hallmark of creatine deficiency disorders

Valongo, Carla; Almeida, Lígia; Ramos, Altina; Santos, Raquel Andreia; Vilarinho, Laura

http://hdl.handle.net/10400.18/4226

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Authors

Valongo, Carla

Almeida, Lígia

Ramos, Altina

Santos, Raquel Andreia

Vilarinho, Laura

Abstract(s)

Introduction: In Western countries, mental retardation (MR) affects about 3% of the general population. For the majority of the cases of inherited MR, the genetic causes are not yet elucidated. Patients with creatine deficiency disorders (CDD) may present with MR/developmental delay as well as expressive speech and language delay, autism and epilepsy. They represent a group of treatable inborn errors of creatine biosynthesis and transport (SLC6A8) across the blood brain barrier. Patients and Methods: A group of children and young adults with MR were studied for defects in creatine metabolism. We started with the determination of guanidinoacetate and creatine in 6,600 urine samples by GC-MS-SIM. DNA mutation analysis was performed in all suspected cases. Results: Urine biochemical analysis revealed seven cases compatible with GAMT deficiency and 15 patients suggestive of a defect in SLC6A8. All GAMT deficient patients show the same mutation which suggests a founder effect in our population. SLC6A8 deficiency patients revealed a large spectrum of mutations. Discussion: So far, 22 patients with CDD were identified in our laboratory (1:300). We believe these defects are still under diagnosed, so the possibility should be considered in all children affected by unexplained MR, seizures, and speech delay.