Dimethylglycine Dehydrogenase Deficiency (DMGDH deficiency; hyperdimethylglycinemia): Comprehensive Disease Characteristics Report

Target disease

• Disease name: Dimethylglycine dehydrogenase deficiency
• Category: Mendelian / inborn error of metabolism (one‑carbon/choline degradation pathway)
• Key identifier available from retrieved sources: OMIM 605850 (reported in mechanistic/structural papers) (augustin2016structureandbiochemical pages 7-9, augustin2016structureandbiochemical pages 1-3)
• MONDO / Orphanet / MeSH / ICD-10/ICD-11: Not identified in the retrieved corpus for this run; these identifiers should be added from external ontology resources during curation (limitation of this tool-run).

Executive summary

Dimethylglycine dehydrogenase deficiency is an ultra‑rare inborn error of choline catabolism/one‑carbon metabolism caused by loss of function in DMGDH, a mitochondrial FAD- and tetrahydrofolate (THF)‑dependent enzyme that oxidatively demethylates N,N‑dimethylglycine (DMG) to sarcosine. The canonical human phenotype is mild and has been described primarily in a single adult patient, featuring a lifelong fish‑like odor, muscle fatigue/weakness, and persistent creatine kinase (CK) elevation, with massively increased DMG in serum and urine. Diagnosis relies on targeted metabolite measurement (historically by ^1H NMR spectroscopy of urine/serum) and confirmatory molecular genetic testing identifying biallelic DMGDH variants (e.g., A326G; p.His109Arg). Evidence for disease mechanism and variant pathogenicity is strengthened by biochemical/structural characterization of the H109R variant showing marked impairment in substrate affinity/cofactor incorporation and catalytic efficiency. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, mcandrew2008molecularbasisof pages 1-3, moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine pages 1-1)

Table: This table condenses the core literature on dimethylglycine dehydrogenase deficiency, including the nomenclature used, the causal gene, the single well-described human case, key quantitative laboratory abnormalities, and the main pathogenic variant with biochemical evidence. It is useful as a quick reference for disease curation and knowledge base population.

1. Disease information

1.1 What is the disease?

Dimethylglycine dehydrogenase deficiency (also called hyperdimethylglycinemia) is a genetic metabolic disorder in which impaired DMGDH activity blocks the mitochondrial step converting DMG to sarcosine, leading to marked accumulation of DMG in body fluids and a mild clinical phenotype in the best‑described patient. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-1, moolenaar1999defectindimethylglycine pages 1-2)

1.2 Common synonyms / alternative names (from primary literature)

• “Dimethylglycine dehydrogenase deficiency” (walker2012trimethylaminuriaanddimethylglycine pages 3-5, augustin2016structureandbiochemical pages 7-9)
• “Hyperdimethylglycinemia” (used as a descriptor for DMG elevation in the discovery paper) (moolenaar1999defectindimethylglycine pages 1-1)
• “Defect in dimethylglycine dehydrogenase” (title/terminology of original case report) (moolenaar1999defectindimethylglycine pages 1-1)

1.3 Evidence source type

The disease description is derived primarily from: - Individual human case report/discovery study using metabolomics/NMR and molecular genetics (moolenaar1999defectindimethylglycine pages 1-1, moolenaar1999defectindimethylglycine pages 1-2) - Authoritative chapter-level synthesis describing rarity, diagnostic approach, and management suggestions (walker2012trimethylaminuriaanddimethylglycine pages 3-5) - Biochemical/structural functional studies of the disease-associated variant (mcandrew2008molecularbasisof pages 1-3, augustin2016structureandbiochemical pages 1-3)

2. Etiology

2.1 Disease causal factors

• Genetic cause: Biallelic pathogenic variants in DMGDH. The index patient was homozygous for A326G, encoding p.His109Arg (H109R). (walker2012trimethylaminuriaanddimethylglycine pages 3-5, mcandrew2008molecularbasisof pages 1-3)
• Mechanistic cause: Loss of DMGDH enzymatic function causing failure of DMG demethylation and consequent accumulation of DMG in blood/urine. (augustin2016structureandbiochemical pages 1-3, moolenaar1999defectindimethylglycine pages 1-1)

2.2 Risk factors

• Genetic: Having biallelic loss‑of‑function or severely hypomorphic variants in DMGDH (autosomal recessive inferred). A chapter review states the disorder is “likely autosomal recessive” and notes “only one case” had been reported at that time. (walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• Environmental: No validated environmental risk factors were identified; symptoms (odor) were reported to worsen with stress/exertion in the index patient (not a cause, but a trigger/modifier of symptom expression). (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2)

2.3 Protective factors / gene–environment interactions

No protective genetic variants or gene–environment interactions specific to disease penetrance were reported in the retrieved literature. Given the extremely limited case count, these remain unknown.

3. Phenotypes

3.1 Reported human phenotypes (best-described index case)

Clinical signs/symptoms - Fish‑like body odor beginning in childhood (age 5) and persisting into adulthood. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2) - Unusual muscle fatigue and/or mild muscle weakness. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, mcandrew2008molecularbasisof pages 1-3, moolenaar1999defectindimethylglycine pages 1-2) - Normal intelligence and generally good health otherwise reported in the original case. (moolenaar1999defectindimethylglycine pages 1-2)

Laboratory abnormalities - Markedly increased DMG in serum and urine (quantified in Table 1 of discovery report). (moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine media 773767bc) - Persistently increased serum/plasma creatine kinase (~4× upper limit of normal). (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2)

Phenotype timing and severity - Age of onset: childhood for odor complaint (age ~5). (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2) - Course: chronic/lifelong in the index patient. (walker2012trimethylaminuriaanddimethylglycine pages 3-5) - Severity: described as mild/non‑fatal in later mechanistic literature. (augustin2016structureandbiochemical pages 7-9)

3.2 Suggested HPO terms (mapping based on described features)

(These are ontology suggestions for curation; HPO IDs not retrieved in this run.) - Fishy body odor / abnormal body odor: Abnormal body odor - Fatigue: Fatigue - Muscle weakness: Muscle weakness - Elevated creatine kinase: Elevated circulating creatine kinase concentration - Increased dimethylglycine: Abnormal circulating metabolite concentration (specific metabolite annotation may require custom term)

3.3 Quantitative phenotype-associated data

Table 1 in the original Clinical Chemistry report provides the key quantitative biochemical phenotype: - Serum DMG: 221 (reported as mmol/L in excerpt) vs reference 1–5 (moolenaar1999defectindimethylglycine pages 4-5) - Urine DMG: 457 and 441 mmol/mol creatinine vs reference 1–26 (for age >2 months) (moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine media 773767bc) - Creatine kinase: 1066 U/L (ref 30–270 U/L) (moolenaar1999defectindimethylglycine pages 1-2)

Visual evidence: Table 1/Figure 5 showing these abnormalities and age-related urine DMG reference distribution are captured as cropped images. (moolenaar1999defectindimethylglycine media 773767bc, moolenaar1999defectindimethylglycine media 214a655b)

3.4 Quality of life impact

The index case reported severe psychosocial impact from persistent odor (qualitative description in follow-on NMR paper). (moolenaar2001invivoand pages 94-98)

4. Genetic / molecular information

4.1 Causal gene

• DMGDH encodes mitochondrial dimethylglycine dehydrogenase, a covalently flavinylated enzyme requiring THF. (augustin2016structureandbiochemical pages 1-3, moolenaar1999defectindimethylglycine pages 1-2)

4.2 Pathogenic variant(s)

• Index disease variant: c.326A>G; p.His109Arg (H109R), homozygous in the reported patient. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, mcandrew2008molecularbasisof pages 1-3)

4.3 Functional consequences (variant-level)

Two independent functional analyses support pathogenicity: - H109R shows reduced flavin incorporation/cofactor saturation, markedly impaired substrate affinity and/or catalytic efficiency, and reduced stability—mechanistic routes to decreased enzymatic flux and DMG accumulation. (mcandrew2008molecularbasisof pages 4-6, augustin2016structureandbiochemical pages 7-9, augustin2016structureandbiochemical pages 1-3) - Quantitatively, one study reports the H109R mutant as having a ~65‑fold increase in Km and ~27‑fold decrease in activity, with overall ~1800‑fold loss in catalytic efficiency (after accounting for flavination), consistent with a severe hypomorphic/LOF allele. (mcandrew2008molecularbasisof pages 4-6)

4.4 Population frequency context

The H109R allele was observed in ExAC at 58/118,656 alleles (0.049%), predominantly in individuals of African descent, highlighting that population presence does not exclude pathogenicity for autosomal recessive disease when homozygosity is rare. (augustin2016structureandbiochemical pages 1-3)

4.5 Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes, epigenetic findings, or chromosomal abnormalities were reported for DMGDH deficiency in the retrieved sources.

5. Environmental information

No established environmental toxins, lifestyle factors, or infectious triggers are reported as causal. Symptom fluctuation with stress/exertion (odor worsening) is noted in the index case. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2)

6. Mechanism / pathophysiology

6.1 Molecular pathway and causal chain

Upstream: Dietary choline → betaine → DMG (as part of choline catabolism / methyl group metabolism).

Core defect: DMGDH is a mitochondrial FAD- and THF-dependent enzyme that demethylates DMG to sarcosine; THF accepts the methyl group (preventing release of formaldehyde). (augustin2016structureandbiochemical pages 1-3)

Downstream biochemical consequence: DMGDH deficiency results in marked accumulation of DMG in serum and urine, and absent/undetectable sarcosine in the original biochemical profile. (moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine pages 1-2)

Clinical consequence (known): fish‑like odor (likely from volatile DMG), fatigue/weakness, and elevated CK. However, because the phenotype is based on very few individuals, links beyond metabolite accumulation remain uncertain. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 5-5)

6.2 Suggested GO biological process / cellular component terms

(ontology suggestions) - GO: one‑carbon metabolic process - GO: choline metabolic process / betaine metabolic process - GO: glycine metabolic process - GO cellular component: mitochondrial matrix (DMGDH is mitochondrial) (augustin2016structureandbiochemical pages 1-3)

6.3 Suggested cell types (Cell Ontology)

No specific cell type pathology is described; enzyme is liver‑relevant in catabolism. For curation, consider: - Hepatocyte (primary site of choline metabolism; inferred, not directly evidenced here) - Skeletal muscle cell (given CK and fatigue; speculative)

7. Anatomical structures affected

7.1 Organ/system level (evidence-based)

• Muscle involvement: suggested by fatigue/weakness and persistently elevated CK. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-2)

7.2 Suggested UBERON terms

• Skeletal muscle tissue (UBERON suggestion)
• Liver (UBERON suggestion; diagnostic enzyme assay discussion implies liver relevance) (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

7.3 Subcellular localization

• Mitochondrial enzyme (matrix-associated) consistent with biochemical characterization. (augustin2016structureandbiochemical pages 1-3)

8. Temporal development

• Onset: childhood for odor (age ~5). (walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• Course: chronic/lifelong; no defined staging described. (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

9. Inheritance and population

9.1 Inheritance

• Inferred autosomal recessive (chapter source: “likely autosomal recessive”; index patient homozygous). (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

9.2 Epidemiology

• Extremely rare; as of the chapter publication, “only one case has been reported.” (walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• No robust incidence/prevalence estimates were identified in the retrieved sources.

9.3 Population/ancestry

• Index case: described as a man of African ancestry. (moolenaar1999defectindimethylglycine pages 1-2)
• H109R allele: enriched in ExAC African ancestry subset. (augustin2016structureandbiochemical pages 1-3)

10. Diagnostics

10.1 Core diagnostic biomarker

• Elevated DMG in plasma/serum and urine is the defining biochemical abnormality. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 4-5)

10.2 Laboratory methods (real-world implementations)

• ^1H NMR spectroscopy of urine and serum was a key diagnostic approach in the discovery study; DMG displayed characteristic singlets (2.93 and 3.80 ppm) and was confirmed by spiking experiments. (moolenaar1999defectindimethylglycine pages 4-5)
• GC‑MS confirmation can be performed, but the discovery paper notes DMG can be missed by routine organic-acid workflows using solvent extraction (lost during ethyl acetate extraction). (moolenaar1999defectindimethylglycine pages 3-4, walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• Fish‑challenge testing and urinary trimethylamine measures were used to exclude trimethylaminuria in the presenting “fish odor” complaint. (moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine pages 3-4)

10.3 Enzyme assay

A chapter notes DMGDH activity is not normally detectable in blood cells/fibroblasts, so confirmatory enzyme testing would require liver tissue (biopsy)—a major practical limitation. (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

10.4 Genetic testing

Confirmatory diagnosis is via DMGDH sequencing to identify biallelic pathogenic variants (e.g., A326G/H109R). (moolenaar1999defectindimethylglycine pages 1-1, walker2012trimethylaminuriaanddimethylglycine pages 3-5)

10.5 Differential diagnosis

Given the presenting symptom of fish-like odor, differential considerations include trimethylaminuria; DMGDH deficiency can be distinguished by massively elevated DMG and low trimethylamine after fish challenge. (moolenaar1999defectindimethylglycine pages 4-5, moolenaar1999defectindimethylglycine pages 3-4)

11. Outcome / prognosis

• Later biochemical/structural literature describes the disorder as non‑fatal and typically mild. (augustin2016structureandbiochemical pages 7-9)
• No survival statistics, long-term organ outcomes, or standardized quality-of-life metrics were identified, due to limited case ascertainment.

12. Treatment

12.1 Evidence-based interventions (limited)

No established disease-modifying therapy exists.

Riboflavin trial (index case): The original report states the patient received riboflavin 10 mg/day for 3 months without clinical improvement. (moolenaar1999defectindimethylglycine pages 3-4)

Supportive/empiric measures (expert opinion from authoritative chapter): - Counseling - Dietary choline restriction and avoidance of excessive sweating (odor management) - Antibiotics to alter intestinal microflora “not indicated” - Suggested trial of folate with riboflavin (hypothesis-driven, not proven) (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

12.2 Suggested MAXO terms

(ontology suggestions) - Dietary modification / dietary choline restriction - Vitamin supplementation (riboflavin; folate) - Genetic counseling

12.3 Clinical trials

No DMGDH deficiency–specific trials were retrieved.

13. Prevention

• Primary prevention: not applicable in the usual sense for an autosomal recessive condition.
• Secondary prevention: early biochemical/genetic diagnosis may reduce psychosocial morbidity by explaining odor and guiding supportive measures. (walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• Genetic counseling: indicated for families once a causative DMGDH genotype is identified (inferred from AR inheritance and chapter guidance). (walker2012trimethylaminuriaanddimethylglycine pages 3-5)

14. Other species / natural disease

No naturally occurring veterinary disease analogs were identified in the retrieved sources.

15. Model organisms / experimental systems

15.1 Human protein functional models

Functional evidence is largely derived from recombinant enzyme studies and structural biology (including a reported PDB structure for human DMGDH in one study). (augustin2016structureandbiochemical pages 1-3)

15.2 Need for in vivo models

The molecular basis paper notes that additional DMGDH‑deficient humans or an appropriate mouse model would be needed to resolve genotype–phenotype questions. (mcandrew2008molecularbasisof pages 8-8)

Recent developments (prioritizing 2023–2024)

Direct 2023–2024 primary case expansions were not available in the retrievable corpus for this run. As a proxy for “latest research” relevant to real‑world implementation, the most concrete near‑term development is the continued mainstreaming of broad metabolomics and sequencing for rare disease diagnosis (with older but still relevant metabolomics evidence in this run). For example, DI‑HRMS metabolomics has been evaluated for inborn errors using dried blood spots and plasma; one limitation noted is that some workflows may fail to recognize DMGDH deficiency depending on feature detection/annotation. (moolenaar2001invivoand pages 98-101)

Key primary sources (URLs and publication dates)

• Moolenaar SH et al. “Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study.” Clinical Chemistry (Apr 1999). https://doi.org/10.1093/clinchem/45.4.459 (moolenaar1999defectindimethylglycine pages 1-1)
• McAndrew R et al. “Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant H109R.” Journal of Inherited Metabolic Disease (Oct 2008). https://doi.org/10.1007/s10545-008-0999-2 (mcandrew2008molecularbasisof pages 1-3)
• Walker V, Wevers RA. “Trimethylaminuria and Dimethylglycine Dehydrogenase Deficiency.” In Inborn Metabolic Diseases (Jan 2012). https://doi.org/10.1007/978-3-540-28785-8_31 (walker2012trimethylaminuriaanddimethylglycine pages 3-5)
• Augustin P et al. “Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant.” FEBS Journal (Oct 2016). https://doi.org/10.1111/febs.13828 (augustin2016structureandbiochemical pages 1-3)

Clinical trials / registries relevant to real-world implementation

• CoRDS (Coordination of Rare Diseases at Sanford) observational registry / natural history infrastructure: NCT01793168 (first posted Feb 2013, recruiting; last update posted May 2025). https://clinicaltrials.gov/study/NCT01793168 (NCT01793168 chunk 2, NCT01793168 chunk 1)

Limitations of the current evidence base

1. The human phenotype and natural history remain weakly defined because the core evidence is dominated by a single well-described individual and secondary summaries. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 1-1)
2. Standard disease identifiers beyond OMIM (e.g., MONDO, Orphanet, ICD, MeSH) were not found in the retrieved set and must be added via direct ontology database queries.
3. Therapeutic guidance is largely expert opinion and hypothesis-driven supplementation trials rather than controlled clinical evidence. (walker2012trimethylaminuriaanddimethylglycine pages 3-5, moolenaar1999defectindimethylglycine pages 3-4)

References

1. (augustin2016structureandbiochemical pages 7-9): Peter Augustin, Altijana Hromic, Tea Pavkov‐Keller, Karl Gruber, and Peter Macheroux. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease‐related h109r variant. The Febs Journal, 283:3587-3603, Oct 2016. URL: https://doi.org/10.1111/febs.13828, doi:10.1111/febs.13828. This article has 27 citations.

2. (augustin2016structureandbiochemical pages 1-3): Peter Augustin, Altijana Hromic, Tea Pavkov‐Keller, Karl Gruber, and Peter Macheroux. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease‐related h109r variant. The Febs Journal, 283:3587-3603, Oct 2016. URL: https://doi.org/10.1111/febs.13828, doi:10.1111/febs.13828. This article has 27 citations.

3. (walker2012trimethylaminuriaanddimethylglycine pages 3-5): Valerie Walker and Ron A. Wevers. Trimethylaminuria and dimethylglycine dehydrogenase deficiency. Inborn Metabolic Diseases, pages 381-385, Jan 2012. URL: https://doi.org/10.1007/978-3-540-28785-8_31, doi:10.1007/978-3-540-28785-8_31. This article has 3 citations.

4. (mcandrew2008molecularbasisof pages 1-3): Ryan McAndrew, Jerry Vockley, and Jung-Ja P. Kim. Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant h109r. Journal of Inherited Metabolic Disease, 31:761-768, Oct 2008. URL: https://doi.org/10.1007/s10545-008-0999-2, doi:10.1007/s10545-008-0999-2. This article has 14 citations and is from a peer-reviewed journal.

5. (moolenaar1999defectindimethylglycine pages 4-5): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

6. (moolenaar1999defectindimethylglycine pages 1-1): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

7. (moolenaar2001invivoand pages 89-94): Sytske H. Moolenaar, Marjo S. van der Knaap, Udo F. H. Engelke, Petra J. W. Pouwels, Fokje S. M. Janssen‐Zijlstra, Nanda M. Verhoeven, Cornelis Jakobs, and Ron A. Wevers. In vivo and in vitro nmr spectroscopy reveal a putative novel inborn error involving polyol metabolism. NMR in Biomedicine, 14:167-176, May 2001. URL: https://doi.org/10.1002/nbm.690, doi:10.1002/nbm.690. This article has 58 citations and is from a peer-reviewed journal.

8. (moolenaar2001invivoand pages 94-98): Sytske H. Moolenaar, Marjo S. van der Knaap, Udo F. H. Engelke, Petra J. W. Pouwels, Fokje S. M. Janssen‐Zijlstra, Nanda M. Verhoeven, Cornelis Jakobs, and Ron A. Wevers. In vivo and in vitro nmr spectroscopy reveal a putative novel inborn error involving polyol metabolism. NMR in Biomedicine, 14:167-176, May 2001. URL: https://doi.org/10.1002/nbm.690, doi:10.1002/nbm.690. This article has 58 citations and is from a peer-reviewed journal.

9. (moolenaar1999defectindimethylglycine pages 1-2): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

10. (moolenaar1999defectindimethylglycine pages 3-4): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

11. (moolenaar1999defectindimethylglycine pages 5-5): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

12. (moolenaar2001invivoand pages 98-101): Sytske H. Moolenaar, Marjo S. van der Knaap, Udo F. H. Engelke, Petra J. W. Pouwels, Fokje S. M. Janssen‐Zijlstra, Nanda M. Verhoeven, Cornelis Jakobs, and Ron A. Wevers. In vivo and in vitro nmr spectroscopy reveal a putative novel inborn error involving polyol metabolism. NMR in Biomedicine, 14:167-176, May 2001. URL: https://doi.org/10.1002/nbm.690, doi:10.1002/nbm.690. This article has 58 citations and is from a peer-reviewed journal.

13. (moolenaar1999defectindimethylglycine media 773767bc): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

14. (mcandrew2008molecularbasisof pages 4-6): Ryan McAndrew, Jerry Vockley, and Jung-Ja P. Kim. Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant h109r. Journal of Inherited Metabolic Disease, 31:761-768, Oct 2008. URL: https://doi.org/10.1007/s10545-008-0999-2, doi:10.1007/s10545-008-0999-2. This article has 14 citations and is from a peer-reviewed journal.

15. (mcandrew2008molecularbasisof pages 6-8): Ryan McAndrew, Jerry Vockley, and Jung-Ja P. Kim. Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant h109r. Journal of Inherited Metabolic Disease, 31:761-768, Oct 2008. URL: https://doi.org/10.1007/s10545-008-0999-2, doi:10.1007/s10545-008-0999-2. This article has 14 citations and is from a peer-reviewed journal.

16. (moolenaar1999defectindimethylglycine media 214a655b): Sytske H Moolenaar, Jo Poggi-Bach, Udo FH Engelke, Jacqueline MB Corstiaensen, Arend Heerschap, Jan GN de Jong, Barbara A Binzak, Jerry Vockley, and Ron A Wevers. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: nmr spectroscopy study. Clinical chemistry, 45 4:459-64, Apr 1999. URL: https://doi.org/10.1093/clinchem/45.4.459, doi:10.1093/clinchem/45.4.459. This article has 100 citations and is from a highest quality peer-reviewed journal.

17. (mcandrew2008molecularbasisof pages 8-8): Ryan McAndrew, Jerry Vockley, and Jung-Ja P. Kim. Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant h109r. Journal of Inherited Metabolic Disease, 31:761-768, Oct 2008. URL: https://doi.org/10.1007/s10545-008-0999-2, doi:10.1007/s10545-008-0999-2. This article has 14 citations and is from a peer-reviewed journal.

18. (NCT01793168 chunk 2): Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford. Sanford Health. 2010. ClinicalTrials.gov Identifier: NCT01793168

19. (NCT01793168 chunk 1): Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford. Sanford Health. 2010. ClinicalTrials.gov Identifier: NCT01793168