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Beta-Ketothiolase Deficiency

Disease Pathophysiology Research Template

2026-02-23
Falcon MONDO:0008760 Model: Edison Scientific Literature 20 citations

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Pathophysiology Research Template

Target Disease

  • Disease Name: Beta-ketothiolase Deficiency
  • MONDO ID: (if available)
  • Category: Genetic

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Beta-ketothiolase Deficiency. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

  • What are the primary pathophysiological mechanisms?
  • What molecular pathways are dysregulated?
  • What cellular processes are affected?

2. Key Molecular Players

  • Genes/Proteins: Which genes are causally involved or implicated?
  • Chemical Entities: What metabolites, drugs, or small molecules are relevant?
  • Cell Types: Which cell types are primarily affected?
  • Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

  • What biological processes (GO terms) are disrupted?
  • Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

  • Where in the cell do key processes occur?
  • Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

  • What is the sequence of events from initial trigger to clinical manifestation?
  • Are there distinct stages or phases?

6. Phenotypic Manifestations

  • What are the key clinical phenotypes?
  • How do they relate to the underlying mechanisms?

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Comprehensive Research Report: Pathophysiology of Beta-ketothiolase Deficiency (BKD)

Publication focus: molecular/cellular mechanisms underlying disease progression, with emphasis on recent (2023–2024) primary/clinical literature and implementation studies.

  1. Disease definition and core concepts

1.1 Nomenclature and disease concept Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in ACAT1, the gene encoding mitochondrial acetoacetyl‑CoA thiolase (also called β-ketothiolase, 3‑oxothiolase, or T2). The disorder affects both ketone body metabolism and isoleucine catabolism. (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 1-2)

Recent definitional statements (verbatim/near-verbatim from sources): - “Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism.” (Zhen et al., 2024; https://doi.org/10.1186/s40842-024-00174-9; published June 2024) (zhen2024diabeticketoacidosisin pages 1-3) - “BKT (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency is a rare metabolic disorder that affects the metabolism of ketone bodies and catabolism of amino acid isoleucine.” (Patra et al., 2023; https://doi.org/10.25259/jped_9_2023; published September 2023) (patra2023ararecase pages 2-3)

1.2 Core biochemical role of ACAT1/T2 (current understanding) ACAT1/T2 catalyzes key thiolase steps at the interface of: - Ketone body handling: it “synthesizes acetoacetyl-CoA from acetyl-CoA in the liver (ketogenesis) and catalyzes acetoacetyl-CoA to acetyl-CoAs in the last step of ketolysis in extrahepatic tissue.” (Patra et al., 2023) (patra2023ararecase pages 2-3) - Isoleucine catabolism: ACAT1/T2 is described as “the only known enzyme that catalyzes the last step in the isoleucine degradation,” cleaving 2‑methyl‑acetoacetyl‑CoA into propionyl‑CoA and acetyl‑CoA. (Patra et al., 2023) (patra2023ararecase pages 2-3)

A 2024 pathway diagram (Figure 1) in Zhen et al. visually places β‑ketothiolase action sites within both isoleucine catabolism and ketone metabolism and explicitly notes “The short red bar denotes the site of action of beta-ketothiolase.” (https://doi.org/10.1186/s40842-024-00174-9; June 2024) (zhen2024diabeticketoacidosisin media 3ab27e16)

  1. Core pathophysiology (molecular and cellular mechanisms)

2.1 Primary pathophysiological mechanisms The primary pathophysiology arises from loss or reduction of mitochondrial ACAT1/T2 activity, which produces: 1) Impaired terminal step of isoleucine catabolism → accumulation of upstream reactive/acidic intermediates. (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin media 3ab27e16) 2) Impaired ketolysis (extrahepatic utilization of ketone bodies) and altered ketone handling → propensity to ketosis/ketoacidosis, especially under catabolic stress. (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin pages 1-3)

Clinically, BKD “most commonly manifests as recurrent ketoacidosis episodes” with episodes “usually triggered by infection, prolonged fasting, or consumption of a ketogenic diet.” (Zhen et al., 2024; June 2024) (zhen2024diabeticketoacidosisin pages 1-3)

2.2 Dysregulated molecular pathways Based on clinical-biochemical evidence, the dysregulated pathways include: - Isoleucine degradation (branched-chain amino acid catabolic pathway segment specific to isoleucine) with block at 2‑methyl‑acetoacetyl‑CoA cleavage by ACAT1/T2. (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin media 3ab27e16) - Ketone body metabolism including the reversible acetoacetyl‑CoA ↔ acetyl‑CoA step and ketolysis in extrahepatic tissues. (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin media 3ab27e16)

2.3 Cellular processes affected At the cellular level, the principal affected processes are mitochondrial intermediary metabolism and redox/energy homeostasis during fasting or illness, when reliance on ketone body production/utilization and amino-acid-derived acetyl‑CoA flux increases. This is reflected clinically as episodic metabolic decompensation with high anion gap metabolic acidosis and ketosis/ketoacidosis. (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 2-3)

  1. Key molecular players

3.1 Genes/Proteins (HGNC) - ACAT1 (acetyl‑CoA acetyltransferase 1; mitochondrial acetoacetyl‑CoA thiolase/T2/β‑ketothiolase) is the causal gene. (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 2-3)

Genotype–phenotype considerations supported by recent clinical series: residual T2 function is associated with milder/less distinctive biochemical abnormalities, whereas loss-of-function genotypes more often show “characteristic” organic acid/acylcarnitine abnormalities. (Anh et al., 2023; https://doi.org/10.52852/tcncyh.v171i10.2016; published Dec 2023) (anh2023đặcđiểmhóa pages 6-8)

3.2 Chemical entities / metabolites (CHEBI-oriented list) Characteristic metabolites (used diagnostically and mechanistically linked to pathway blockade): Urine organic acids: - 2‑methyl‑3‑hydroxybutyrate (2M3HB) (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 6-8) - 2‑methylacetoacetate (2MAA) (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 6-8) - Tiglylglycine (TIG) (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 6-8) Blood acylcarnitines: - Tiglylcarnitine (C5:1) and 2‑methyl‑3‑hydroxybutyryl‑carnitine (often aligned with C5:OH patterns in screening contexts) (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 8-8) Additional crisis-associated ketone-related molecules: - Acetoacetate and β‑hydroxybutyrate are reported among urinary elevations in crisis contexts. (patra2023ararecase pages 2-3)

Stability/measurement caveat (important for interpreting biochemical data): 2MAA can be missed because “2MAA is unstable on filter paper” (degrading to 2‑butanone), so dried urine spots may under-detect this metabolite. (Anh et al., 2023; Dec 2023) (anh2023đặcđiểmhóa pages 6-8)

3.3 Cell types (CL terms; inferred from clinical physiology) Direct cell-type-specific mechanistic studies were not available in the retrieved 2023–2024 BKD-focused texts. However, clinical physiology and the cited mechanistic hypotheses indicate particular relevance of: - Hepatocytes (liver ketogenesis context) and extrahepatic oxidative tissues that perform ketolysis. (patra2023ararecase pages 2-3) - Pancreatic endocrine cells (β-cells) are implicated indirectly through observed dysglycemia/hyperglycemia in decompensations and hypothesized effects of organic acid accumulation on pancreatic function. (zhen2024diabeticketoacidosisin pages 3-5)

3.4 Anatomical locations (UBERON terms) - Liver: implicated through ketogenesis (“in the liver (ketogenesis)”). (patra2023ararecase pages 2-3) - Extrahepatic tissues: ketolysis impairment occurs “in extrahepatic tissue.” (patra2023ararecase pages 2-3) - Pancreas: hypothesized vulnerability—Zhen et al. cite a postulate that “accumulation of organic acids in the pancreas may predispose to diabetes by impairing the structure and normal functionality of the pancreas.” (Zhen et al., 2024; June 2024) (zhen2024diabeticketoacidosisin pages 3-5)

  1. Biological processes (GO annotation candidates) The following GO biological process concepts are supported by evidence from the retrieved sources:
  2. Branched-chain amino acid catabolic process / isoleucine catabolic process (pathway block at 2‑methyl‑acetoacetyl‑CoA processing) (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin media 3ab27e16)
  3. Ketone body metabolic process (ketogenesis and ketolysis-related steps; recurrent ketoacidosis phenotype) (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin pages 1-3)
  4. Response to starvation/fasting (clinical triggers: prolonged fasting; crisis prevention includes fasting avoidance) (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 1-2)

  5. Organic acid metabolic process / cellular acid-base homeostasis (clinical biochemical phenotype: high anion gap metabolic acidosis) (patra2023ararecase pages 2-3, patra2023ararecase pages 1-2)

  6. Cellular components (GO cellular component candidates)

  7. Mitochondrion (mitochondrial enzyme; explicitly described as “mitochondrial acetoacetyl‑CoA thiolase”) (patra2023ararecase pages 2-3)

  8. Mitochondrial matrix (not explicitly quoted in the BKD-specific recent papers retrieved; however, the enzyme is consistently described as mitochondrial, and related mitochondrial metabolic context is shown in pathway diagrams) (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin media 3ab27e16)

  9. Disease progression model (trigger → molecular events → clinical crisis)

6.1 Triggering conditions Acute crises are commonly triggered by catabolic stressors: infection, prolonged fasting, or ketogenic diets. (Zhen et al., 2024; June 2024) (zhen2024diabeticketoacidosisin pages 1-3)

6.2 Sequence of events (mechanistic-to-clinical) 1) Trigger increases reliance on ketone body flux and amino acid catabolism. 2) ACAT1/T2 functional block causes accumulation of characteristic isoleucine-catabolic/ketone-related organic acids (2M3HB, TIG, 2MAA) and related acylcarnitines. (zhen2024diabeticketoacidosisin pages 1-3, zhen2024diabeticketoacidosisin media 3ab27e16) 3) Accumulated organic acids contribute to high anion gap metabolic acidosis with ketosis/ketoacidosis and may be associated with fluctuating glucose (hypo-/hyperglycemia). (patra2023ararecase pages 2-3, patra2023ararecase pages 1-2) 4) Clinical decompensation presents as episodic ketoacidosis, often in infancy/early childhood, with intervals of relative wellness; episodes tend to reduce in frequency with age and are reported as rare after age 10 in classic descriptions. (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 8-8)

6.3 Stages/phases - Intercritical/asymptomatic phase: may have normal metabolic testing; even individuals with null mutations can show normal urine organic acids and blood acylcarnitines when clinically well, and variants with residual function may be difficult to detect even during crisis. (zhen2024diabeticketoacidosisin pages 1-3) - Acute decompensation phase: ketoacidosis episodes with characteristic metabolite patterns, but with documented variability in marker presence/intensity across patients. (anh2023đặcđiểmhóa pages 6-8, anh2023đặcđiểmhóa pages 8-8)

  1. Phenotypic manifestations and mechanistic links

7.1 Core clinical phenotypes (HP-oriented) - Episodic ketoacidosis / acute metabolic decompensation: “recurrent episodes of ketoacidosis” (Zhen et al., 2024) and “episodes of acute ketoacidosis” with well intervals (Anh et al., 2023). (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 8-8) - High anion gap metabolic acidosis, potentially severe (e.g., pH 6.99 in an infant case). (patra2023ararecase pages 2-3) - Seizures, coma, shock may occur in severe pediatric presentations, consistent with metabolic encephalopathy/critical illness physiology. (patra2023ararecase pages 1-2) - Glucose dysregulation: episodes may mimic diabetic ketoacidosis with hyperglycemia; Zhen et al. report the first adult case of diabetes presenting with DKA in BKD and emphasize HbA1c evaluation for persistent dysglycemia. (zhen2024diabeticketoacidosisin pages 1-3)

7.2 Diagnostic pitfalls as phenotypic modifiers - Dipstick ketone testing may be negative early in presentation despite severe acidosis; later ketonuria can appear, creating diagnostic confusion with diabetic ketoacidosis. (patra2023ararecase pages 1-2) - Biomarker sensitivity limitations: MS/MS blood acylcarnitine screening is not 100% sensitive, and the full urine organic acid “triad” may be absent; this may delay diagnosis and affect outcomes. (anh2023đặcđiểmhóa pages 8-8, anh2023đặcđiểmhóa pages 6-8)

  1. Recent developments and latest research (2023–2024)

8.1 Adult presentations and dysglycemia: expanding phenotype spectrum (2024) Zhen et al. (June 2024) report the first described adult case of diabetes presenting as DKA in BKD and propose practice changes: “importance of checking HbA1c in people with BKD and hyperglycemia” to detect coexisting diabetes. (https://doi.org/10.1186/s40842-024-00174-9; June 2024) (zhen2024diabeticketoacidosisin pages 1-3)

Mechanistic hypothesis raised: organic acids may accumulate and potentially impair pancreatic structure/function (“postulated … accumulation of organic acids in the pancreas may predispose to diabetes”). (zhen2024diabeticketoacidosisin pages 3-5)

8.2 Newborn screening (NBS) epidemiology and BKD incidence estimates (2024) A large MS/MS newborn screening cohort (Huaihua, China; 206,977 newborns screened 2015–2021) reported: - 5,578 initial positives (2.69%), 4,085 recalls (73.23% of positives), 297 referred for diagnostic testing, and 69 confirmed IEM cases (overall incidence ~1:3,000). (Frontiers in Genetics; https://doi.org/10.3389/fgene.2024.1387423; May 2024) (xiao2024206977newbornscreening pages 5-7) - Within FAODs, beta‑ketothiolase deficiency incidence was reported as 1:32,237, observed only in the Miao ethnic subgroup in that cohort. (xiao2024206977newbornscreening pages 5-7) These are actionable statistics for population-level planning and for assessing inclusion in expanded NBS panels. (xiao2024206977newbornscreening pages 5-7)

8.3 Implementing genetic second-tier testing to reduce NBS false positives (2024) A Hong Kong program implemented an amplicon-based NGS second-tier panel including BKD among six IEMs (screening period 1 Sept 2021–31 Aug 2022). Key operational outcomes: - Second-tier genetic testing was performed for 1.8% of 22,883 NBS samples. - The overall false-positive rate across those six conditions after NGS second-tier testing was 0.017%, with “no false negatives reported.” (International Journal of Neonatal Screening; https://doi.org/10.3390/ijns10010019; published 5 March 2024) (chan2024harnessingnextgenerationsequencing pages 1-2) While BKD-specific yields were not detailed in the excerpt, this represents a real-world implementation approach relevant to improving BKD detection while minimizing unnecessary recalls. (chan2024harnessingnextgenerationsequencing pages 1-2)

  1. Current applications and real-world implementations

9.1 Diagnostics in clinical practice Evidence-supported diagnostic workflow: - During acute episodes: urine organic acids (GC/MS) plus blood acylcarnitines (MS/MS) can be “confirmatory” in pediatric presentations and are emphasized as hallmark tools. (patra2023ararecase pages 1-2) - Confirmatory testing: ACAT1 gene sequencing and/or enzyme activity assays in patient cells. (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 2-3)

Real-world diagnostic performance limitations: - Vietnamese case-series data show biochemical screening variability: in 23 symptomatic patients screened by blood acylcarnitines, 2/23 had neither C5:1 nor C5:OH elevation, indicating incomplete sensitivity. (Anh et al., Dec 2023) (anh2023đặcđiểmhóa pages 8-8) - Urine organic acids also vary: 2M3HB elevated in 23/26, TIG 13/26, and 2MAA 6/26, with the classic triad not universal. (anh2023đặcđiểmhóa pages 6-8)

9.2 Acute management (“sick-day” and crisis treatment) Recent expert recommendations converge on: - Acute crisis: intravenous dextrose “to suppress ketogenesis (even if euglycemic),” plus fluids/electrolytes/supportive care. (Zhen et al., June 2024) (zhen2024diabeticketoacidosisin pages 1-3) - Pediatric severe crises may require insulin infusion (for DKA-like states), bicarbonate correction, and intensive supportive care, including ventilation/dialysis when required. (Patra et al., 2023) (patra2023ararecase pages 2-3)

9.3 Chronic management and prevention - Avoid fasting; ensure regular carbohydrate intake; avoid ketogenic diets. (zhen2024diabeticketoacidosisin pages 1-3) - Consider carnitine supplementation if deficient. (zhen2024diabeticketoacidosisin pages 1-3) - Dietary approach in one recent pediatric report includes “mild protein restriction” with avoidance of excess fat intake and sick-day glucose/electrolyte solutions. (patra2023ararecase pages 2-3)

  1. Expert opinions and analysis (authoritative sources, 2023–2024)

10.1 Diagnostic caution: BKD can mimic DKA Patra et al. (2023) emphasize that BKD can clinically mimic diabetic ketoacidosis and that atypical features (e.g., persistent acidosis, fluctuating glucose, normal HbA1c/C-peptide) should prompt evaluation for inborn errors of metabolism, to prevent “death or permanent neurological complications.” (patra2023ararecase pages 2-3)

10.2 Surveillance for persistent dysglycemia in BKD Zhen et al. (2024) highlight the practice implication that HbA1c should be checked in BKD patients with hyperglycemia to uncover coexisting diabetes and prevent complications. (zhen2024diabeticketoacidosisin pages 1-3)

10.3 Screening strategy interpretation Anh et al. (2023) explicitly state MS/MS acylcarnitine screening “không đảm bảo độ nhạy 100%” (does not ensure 100% sensitivity), and recommend urine organic acid analysis to confirm diagnosis even when screening is normal but clinical suspicion persists. (anh2023đặcđiểmhóa pages 6-8)

  1. Relevant statistics and data (recent studies)

11.1 Biomarker frequencies in a 2017–2023 clinical cohort (Vietnam; published Dec 2023) In 26 patients with BKD, urine GC/MS showed: - 2M3HB elevated: 23/26 - TIG elevated: 13/26 - 2MAA elevated: 6/26 (Anh et al., 2023) (anh2023đặcđiểmhóa pages 6-8)

In 23 patients screened by blood acylcarnitines (MS/MS): - C5:1 elevated: 19/23 - C5:OH elevated: 20/23 - Both elevated: 18/23 - Neither elevated: 2/23 (Anh et al., 2023) (anh2023đặcđiểmhóa pages 8-8)

11.2 NBS incidence estimate in a large Chinese cohort (published May 2024) In 206,977 newborns screened by MS/MS: - BKD incidence was reported as 1:32,237 in this cohort (detected only in Miao subgroup). (xiao2024206977newbornscreening pages 5-7)

11.3 NGS second-tier testing operational metrics (published March 2024) In 22,883 screened newborns, NGS second-tier testing applied to 1.8% of samples yielded an overall false-positive rate of 0.017% across six IEMs and “no false negatives reported.” (chan2024harnessingnextgenerationsequencing pages 1-2)

  1. Knowledge-base-style annotations (ontology-oriented)

12.1 Pathophysiology summary (knowledge-base narrative) Biallelic ACAT1 pathogenic variants reduce mitochondrial acetoacetyl‑CoA thiolase (T2/β‑ketothiolase) activity. This blocks the terminal step of isoleucine degradation (2‑methyl‑acetoacetyl‑CoA → propionyl‑CoA + acetyl‑CoA) and disrupts ketone body metabolism, including ketolysis in extrahepatic tissues. Under catabolic triggers (infection, fasting, ketogenic diets), toxic organic acids and ketone-related intermediates accumulate, producing episodic high anion gap metabolic acidosis with ketosis/ketoacidosis and variable glycemia; between crises, biochemical profiles may normalize, complicating detection. (patra2023ararecase pages 2-3, zhen2024diabeticketoacidosisin pages 1-3)

12.2 Gene/protein annotations - ACAT1 (HGNC: acetyl‑CoA acetyltransferase 1) — causal gene; encodes mitochondrial acetoacetyl‑CoA thiolase (T2). (zhen2024diabeticketoacidosisin pages 1-3, patra2023ararecase pages 2-3)

12.3 GO terms (candidate list; evidence-backed) - Ketone body metabolic process (supported by explicit ketogenesis/ketolysis role and ketoacidosis phenotype) (patra2023ararecase pages 2-3) - Isoleucine catabolic process / branched-chain amino acid catabolic process (supported by explicit statement of terminal isoleucine degradation step) (patra2023ararecase pages 2-3) - Mitochondrial metabolic process (enzyme is mitochondrial; crisis pathophysiology is mitochondrial intermediary metabolism under catabolic stress) (patra2023ararecase pages 2-3)

12.4 Cellular components - Mitochondrion (explicitly “mitochondrial acetoacetyl‑CoA thiolase”) (patra2023ararecase pages 2-3)

12.5 Cell types (candidate list; inferential) - Hepatocyte (ketogenesis context in liver) (patra2023ararecase pages 2-3) - Ketolytic extrahepatic oxidative cell types (e.g., muscle cells, renal cortex) — not directly specified in retrieved texts; supported only at the level of “extrahepatic tissue” ketolysis wording. (patra2023ararecase pages 2-3) - Pancreatic endocrine cell (β-cell) — implicated by dysglycemia observations/hypothesis but not directly studied in retrieved evidence. (zhen2024diabeticketoacidosisin pages 3-5)

12.6 Anatomical locations - Liver (ketogenesis role) (patra2023ararecase pages 2-3) - Extrahepatic tissues (ketolysis role) (patra2023ararecase pages 2-3) - Pancreas (hypothesized organic-acid accumulation affecting function; adult dysglycemia context) (zhen2024diabeticketoacidosisin pages 3-5)

12.7 Chemical entities (CHEBI; key biomarkers) - Tiglylglycine (TIG) (zhen2024diabeticketoacidosisin pages 1-3) - 2‑methyl‑3‑hydroxybutyrate (2M3HB) (zhen2024diabeticketoacidosisin pages 1-3) - 2‑methylacetoacetate (2MAA) (zhen2024diabeticketoacidosisin pages 1-3) - Tiglylcarnitine (C5:1) and 2‑methyl‑3‑hydroxybutyryl‑carnitine / C5:OH pattern (zhen2024diabeticketoacidosisin pages 1-3, anh2023đặcđiểmhóa pages 8-8)

  1. Evidence items (PMID notes) The retrieved evidence set contained DOIs and URLs, but PMIDs were not provided in the extracted text segments. Key 2023–2024 sources used here:
  2. Zhen et al., Clinical Diabetes and Endocrinology (June 2024). DOI: 10.1186/s40842-024-00174-9. URL: https://doi.org/10.1186/s40842-024-00174-9 (zhen2024diabeticketoacidosisin pages 1-3)
  3. Patra et al., Journal of Pediatric Endocrinology and Diabetes (Sept 2023). DOI: 10.25259/jped_9_2023. URL: https://doi.org/10.25259/jped_9_2023 (patra2023ararecase pages 1-2)
  4. Anh et al., Tạp chí Nghiên cứu Y học (Dec 2023). DOI: 10.52852/tcncyh.v171i10.2016. URL: https://doi.org/10.52852/tcncyh.v171i10.2016 (anh2023đặcđiểmhóa pages 6-8)
  5. Xiao et al., Frontiers in Genetics (May 2024). DOI: 10.3389/fgene.2024.1387423. URL: https://doi.org/10.3389/fgene.2024.1387423 (xiao2024206977newbornscreening pages 5-7)
  6. Chan et al., International Journal of Neonatal Screening (published 5 March 2024). DOI: 10.3390/ijns10010019. URL: https://doi.org/10.3390/ijns10010019 (chan2024harnessingnextgenerationsequencing pages 1-2)

Limitations of this report - MONDO ID, OMIM/Orphanet IDs, and PMIDs were not retrievable from the available tool outputs in this run; the report therefore relies on DOI-based identification for the 2023–2024 sources. - Cell-type-resolved molecular mechanisms (e.g., direct mitochondrial stress signaling, ROS, or organ-specific pathology beyond metabolic decompensation physiology) were not present in the retrieved 2023–2024 BKD-focused evidence; additional basic-science literature would be needed for deeper cellular mechanism granularity.

References

  1. (zhen2024diabeticketoacidosisin pages 1-3): Xi May Zhen, Stephen M. Twigg, Ted Wu, Eddy Tabet, Margaret J. McGill, Maria Constantino, Amali Mallawaarachchi, Connie Luo, Senthil Thillainadesan, Yusof Rahman, and Jencia Wong. Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (bkd) involving a novel acat1 variant : first report of established diabetes in bkd and a review of the literature. Clinical Diabetes and Endocrinology, Jun 2024. URL: https://doi.org/10.1186/s40842-024-00174-9, doi:10.1186/s40842-024-00174-9. This article has 5 citations and is from a peer-reviewed journal.

  2. (patra2023ararecase pages 1-2): Bijoy Patra, Shamitha Rangrajan, Sayeeksha Kotekar, and Vishal Malhotra. A rare case of β-ketothiolase deficiency presenting as mimicker of diabetic ketoacidosis. Journal of Pediatric Endocrinology and Diabetes, 3:78-81, Sep 2023. URL: https://doi.org/10.25259/jped_9_2023, doi:10.25259/jped_9_2023. This article has 5 citations.

  3. (patra2023ararecase pages 2-3): Bijoy Patra, Shamitha Rangrajan, Sayeeksha Kotekar, and Vishal Malhotra. A rare case of β-ketothiolase deficiency presenting as mimicker of diabetic ketoacidosis. Journal of Pediatric Endocrinology and Diabetes, 3:78-81, Sep 2023. URL: https://doi.org/10.25259/jped_9_2023, doi:10.25259/jped_9_2023. This article has 5 citations.

  4. (zhen2024diabeticketoacidosisin media 3ab27e16): Xi May Zhen, Stephen M. Twigg, Ted Wu, Eddy Tabet, Margaret J. McGill, Maria Constantino, Amali Mallawaarachchi, Connie Luo, Senthil Thillainadesan, Yusof Rahman, and Jencia Wong. Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (bkd) involving a novel acat1 variant : first report of established diabetes in bkd and a review of the literature. Clinical Diabetes and Endocrinology, Jun 2024. URL: https://doi.org/10.1186/s40842-024-00174-9, doi:10.1186/s40842-024-00174-9. This article has 5 citations and is from a peer-reviewed journal.

  5. (anh2023đặcđiểmhóa pages 6-8): Mai Quỳnh Anh, Trần Thị Thu Mai, Nguyễn Thị Phương Thùy, and Nguyễn Thị Kim Đông. Đặc điểm hóa sinh của bệnh nhân thiếu beta-ketothiolase. Tạp chí Nghiên cứu Y học, 171:150-157, Dec 2023. URL: https://doi.org/10.52852/tcncyh.v171i10.2016, doi:10.52852/tcncyh.v171i10.2016. This article has 0 citations.

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