GLYCTK

Inheritance Pattern: AR

Disease ID:MONDO:0009070

Submitter: ClinGen

Autosomal recessive D-glyceric aciduria was first reported in 1974 (Brandt NJ et al., PMID: 4434100); however, the causative gene and variant were not identified until 2010 (Sass JO et al., PMID: 20949629). Several patients have been described in the literature, the majority based primarily on biochemical findings without accompanying genomic data. The reported clinical spectrum is highly variable, ranging from severe, progressive infantile encephalopathy to a nearly asymptomatic condition. Subsequent investigations have provided additional insights into the etiology of symptoms described in earlier reports. For example, Swanson MA et al. (PMID: 28462797) demonstrated that the nonketotic hyperglycinemia phenotype reported by Brandt NJ et al. (PMID: 4434100) and Sass JO et al. (PMID: 20949629) was attributable to a homozygous missense variant in *AMT* (c.350C>T; p.Ser117Leu). Similarly, Kingma SDK et al. (PMID: 39619776) reported a patient whose hearing loss was attributed to a homozygous pathogenic variant in *STRC* (c.4837G>T; p.Glu1613*). These findings make it unclear whether the clinical features described across reports represent a consistent phenotype attributable to *GLYCTK*, or whether they were influenced by additional genomic findings that were not assessed in earlier studies. The most consistent phenotypic feature curated for this disease entity is the accumulation of D-glycerate in urine, and in some cases serum and cerebrospinal fluid, detected by urine organic acid analysis. To date, four variants (all frameshift) have been reported across three publications (PMID: 4434100; PMID: 20949629; PMID: 39619776) and are included in this curation. The proposed disease mechanism is loss of function, supported by in vitro functional expression studies in HEK293 cells demonstrating that mutant proteins were not expressed and lacked enzymatic activity (Sass JO et al., PMID: 20949629). In summary, there is moderate evidence supporting a gene–disease relationship between *GLYCTK* and autosomal recessive D-glyceric aciduria. This classification was approved by the ClinGen IEM GCEP at the meeting on December 12, 2025 (SOP Version 11).

Inheritance Pattern: AR

Disease ID:MONDO:0009070

Submitter: PanelApp Australia

Inheritance Pattern: AR

Disease ID:MONDO:0009070

Submitter: Orphanet

Inheritance Pattern: AR

Disease ID:MONDO:0009070

Submitter: Labcorp Genetics (formerly Invitae)