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

Modi, Bhavi P.; Khan, Haq Nawaz; Lee, Robin van der; Wasim, Muhammad; Haaxma, Charlotte A.; Richmond, Phillip A.; Drögemöller, Britt I.; Shah, Suleman; Salomons, Gajja S.; Kloet, Frans van der; Vaz, Frédéric M.; Crabben, Saskia N. van der; Ross, Colin J.; Wasserman, Wyeth W.; Awan, Fazli Rabbi

doi:10.1016/j.ymgmr.2021.100761

Cited by 9 publications

(10 citation statements)

References 28 publications

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“…CCDS2 in an adult patient was first described in 2003, and an estimated 25 cases have been reported since then. Children with CCDS2 should receive timely treatment to reduce the risk of developing severe mental and intellectual disabilities in adulthood ( 5 , 15 , 16 , 27 ). In the present study, Patient 1 was diagnosed at the age of 4 years and had a normal developmental outcome after >10 years of treatment.…”

Section: Discussionmentioning

confidence: 99%

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Sun¹,

Wang²,

Wu³

et al. 2023

Transl Pediatr

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Background This study sought to analyze the clinical characteristics, biochemical metabolic indications, treatment results, and genetic spectrum of cerebral creatine deficiency syndrome (CCDS), estimate the prevalence of CCDS in Chinese children and provide a reference to guide clinical practice. Methods We performed a retrospective cohort study of 3,568 children with developmental delay at Children’s Hospital of Fudan University over a 6-year period (January 2017–December 2022). Metabolites in the blood/urine were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and genetic testing was performed by next-generation sequencing (NGS). The patients with suspected CCDS were ultimately diagnosed by magnetic resonance spectroscopy (MRS). The patients were then treated and followed up. All the reported cases of CCDS, their gene mutations, and treatment results in China were summarized. Results Ultimately, 14 patients were diagnosed with CCDS. The age of onset was between 1–2 years. All the patients had developmental delay, 9 had epilepsy, and 8 had movement or behavioral disorders. A total of 17 genetic variants were identified, including 6 novel variants. c.403G>A, c.491dupG of the guanidinoacetate methyltransferase ( GAMT ) gene had a relatively high frequency. After treatment, patients with GAMT deficiency showed obvious improvements, and brain creatine (Cr) levels recovered to 50–80% of normal, 1 patient achieved normal neurodevelopment, and 3 patients became epilepsy free; however, 6 male patients with X-linked creatine transporter gene ( SLC6A8 ) variants received Cr for 3–6 months with no effect, and 2 patients received combined therapy with few improvements. Conclusions The prevalence of CCDS is ~0.39% in Chinese children with developmental delay. A low-protein diet, Cr and, ornithine were useful for patients with GAMT deficiency. Male patients with SLC6A8 deficiency showed only limited improvement on combined therapy.

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Section: Discussionmentioning

confidence: 99%

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Sun¹,

Wang²,

Wu³

et al. 2023

Transl Pediatr

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“…Several nations are screening different IEMs according to their prevalence in that population [83,84] as presented in Table 3 with three most prevalent groups of disorders. In our country (Pakistan), there is no newborn screening program yet available for the screening of inherited metabolic disorders, hence we are making efforts to establish NBS in our country, [9,42,45,62,[85][86][87][88][89] although scarce data are available on such disorders in Pakistan. [9,62,[85][86][87][88][90][91][92][93][94] On the other hand, reports from Pakistan show that burden of inherited disorders is quite high due to consanguinity, hence there is a dire need to develop a NBS program, which can help to minimize the burden of such disorders from the society especially focus on aminoacidopathies, organic acidemias, and fatty acid oxidation disorders.…”

Section: Efforts To Initiate Nbs Program In Asian and Other Countriesmentioning

confidence: 99%

Need and Challenges in Establishing Newborn Screening Programs for Inherited Metabolic Disorders in Developing Countries

et al. 2023

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Even in this post genomic era, no national level newborn screening (NBS) programs for inborn errors of metabolism (IEMs) are yet available in several developing countries including Pakistan. Through NBS, various IEMs can be screened using minute quantities of biofluids. Targeted metabolomics and genomic techniques are the main approaches used for NBS. However, lack of technical expertise and such high-end "omics" based analytical facilities, and meager funding for healthcare in developing countries are the major reasons for unavailability of NBS programs. As it is reflected by only a handful reports about IEMs from Pakistan with population of ≈220 million and consanguinity rate of about 70%, which suggests an unmet need for an NBS program owing to reasonably high prevalence of inherited diseases. Around 200 IEMs are potentially treatable if diagnosed at an earlier stage through biochemical marker and genetic screening, so such patients can get benefit from the NBS program. This overview will help to persuade the stakeholders to setup NBS programs in developing countries including Pakistan, due to multitude of benefits for IEMs; timely diagnosis and early treatment can help the patients to live a nearly healthy life, reduced suffering of the family and minimal burden on society or national healthcare system.

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“…Furthermore, it has been reported that amino acids are also involved in major depressive disorders that can be screened by amino acid profiling [34], so the current method can also help to screen such types of disorders. Thus, there is a need for an NBS program in developing countries like Pakistan because the main goal of the NBS program is to reduce the morbidity and mortality of different inborn metabolic disorders [35][36][37][38][39][40][41][42], so such sensitive and specific analytical methods will be helpful in these efforts. Efficient analytical methods like the one reported in the current study can be applied in the NBS program to identify affected children with diseases like BCAAs, PKU, Maple Syrup Urine Disease, Tyrosinemia type II, Citrullinemia type I and type II, etc.…”

Section: Applications Of This Assaymentioning

confidence: 99%

High‐performance liquid chromatography‐based assay optimization for the detection of plasma amino acids for applications in metabolic disorders in developing countries

Wasim,

Khan,

Tawab

et al. 2023

Separation Science Plus

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Plasma amino acids are generally analyzed through ion exchange chromatography, a reproducible but time‐consuming method. Here, we report the optimization of a reverse‐phase‐high‐performance liquid chromatography with fluorescence detector (RP‐HPLC‐FLD) assay for the detection and quantification of plasma amino acids for potential applications in metabolic disorders (e.g., aminoacidopathies, a rare group of Inborn Errors of Metabolism). For assay development, initially standard amino acids were derivatized with ortho‐phthalaldehyde‐3‐mercaptopropionic acid (OPA‐3‐MPA) and filtered through a 0.20 μm syringe filter. The excitation and emission wavelengths of 240–450 nm (λex—λem) were used for the detection of amino acids. Chromatographic separation was achieved by gradient RP‐HPLC‐FLD through C18 symmetry column (150 × 4.6 mm, particle size 3.5 μm). HPLC assay was successfully optimized and was able to detect amino acids in the range of 10–400 ng/mL and good linearity (R2 > 0.98) was achieved in the mixture for each standard amino acid. Moreover, the current assay showed great efficiency with two additional advantages: the use of low‐cost mobile phases, and the detection and quantification of amino acids at low level (ng/mL) concentration in biofluids. This assay could be applied for the analysis of human plasma to identify aminoacidopathies in newborn screening programs, and other metabolic disorders.

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

Cited by 9 publications

References 28 publications

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Need and Challenges in Establishing Newborn Screening Programs for Inherited Metabolic Disorders in Developing Countries

High‐performance liquid chromatography‐based assay optimization for the detection of plasma amino acids for applications in metabolic disorders in developing countries

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