Mitochondrial 2-methylacetoacetyl-CoA thiolase (ACAT1) deficiency—also called beta-ketothiolase (BKT) deficiency and sometimes described in older literature as showing “potassium-stimulated” metabolite excretion on certain urine tests. This disorder impairs the body’s handling of the amino acid isoleucine and ketone bodies, leading to intermittent, sometimes severe ketoacidosis—often during illness or fasting. Early recognition, avoidance of catabolic stress, rapid glucose support, careful acid–base correction, and carnitine supplementation are the pillars of care; with good management, many people do well. MedlinePlus+2Orpha+2
ACAT1 deficiency is a rare, inherited metabolic condition where a mitochondrial enzyme (acetoacetyl-CoA thiolase, sometimes called T2) does not work properly. Because of this, the body cannot fully break down isoleucine (a building block of proteins) or use ketones efficiently for energy. During stress—like fever, vomiting, or going many hours without food—harmful acids build up in the blood (ketoacidosis). Symptoms in babies and young children may include vomiting, fast or difficult breathing, sleepiness, dehydration, and sometimes seizures; between attacks, many children can be well. Lifelong care focuses on preventing catabolic states, giving extra carbohydrates when sick, and correcting acid–base and carnitine problems quickly during a crisis. MedlinePlus+2Newborn Screening+2
Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency is an inherited problem with an enzyme inside cell “power plants” (mitochondria). The enzyme is called acetoacetyl-CoA thiolase or T2. It is made by the ACAT1 gene. When this enzyme is weak or missing, the body has trouble breaking down the amino acid isoleucine and also has trouble using ketone bodies during fasting or illness. As a result, acids build up in the blood and urine and people, usually infants or young children, can have sudden attacks of severe ketoacidosis with vomiting, fast breathing, sleepiness, and sometimes coma. Between attacks, many children are well. With good care and fast treatment during illnesses, many people do well long-term. MedlinePlus+2BioMed Central+2
Why “potassium-stimulated” matters.
This particular thiolase is activated by potassium (K⁺) ions in the test tube. Lab teams use a potassium-activated enzyme assay to confirm the diagnosis, because T2 is the only human thiolase that turns on with K⁺. In proven patients, “potassium-activated acetoacetyl-CoA thiolase activity” is absent or very low. That is why you may see this disorder described with “potassium-stimulated” in its name. American Chemical Society Publications+2Orpha+2
A unique feature of this enzyme is that it is activated by potassium ions (K⁺). That is why some sources describe it as “potassium-stimulated” or “potassium-activated” thiolase. This is a biochemical property of the enzyme itself and helps explain the wording you may see in newborn-screening materials. PubMed+2American Chemical Society Publications+2
Other names
Beta-ketothiolase deficiency (BKT or BKTD)
2-methylacetoacetyl-CoA thiolase deficiency (MATD)
Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency
ACAT1 deficiency
Inborn error of isoleucine catabolism and ketolysis
Mitochondrial potassium-activated acetoacetyl-CoA thiolase deficiency (reflects the K⁺ activation property) Orpha+2Orpha+2
Types
Intermittent ketoacidotic type.
Most people have sudden attacks of high-anion-gap metabolic acidosis triggered by “ketogenic stress” such as fasting or infection, with normal health between episodes. PubMedInfant/early-childhood onset.
First crises usually happen from 6 months to 3 years when fasting tolerance is still low and infections are common. PubMedNeurologic-predominant or “metabolic stroke” type.
Some children develop movement problems or basal-ganglia injury on MRI during or after crises; rarely the MRI is abnormal even when symptoms are mild. PMC+1Asymptomatic or mild type.
A number of individuals found by newborn screening or family testing remain well with little or no crisis if preventive steps are used. Overall, outcomes can be more favorable than in many other organic acidemias. BioMed CentralBy residual enzyme activity (laboratory type).
Some patients have no measurable K⁺-activated T2 activity; others retain small amounts. This often tracks with severity but clear genotype–phenotype rules are limited. Nature+1
Causes
Biallelic ACAT1 gene variants (the root cause).
Two faulty copies of ACAT1 reduce or stop T2 function. This is the underlying genetic cause. MedlinePlusBlocked ketone use.
Without T2, tissues cannot use ketones efficiently, so ketones and acids rise during stress. PubMedBlocked isoleucine breakdown.
Isoleucine intermediates (2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, tiglylglycine) build up and acidify blood. PMCKetogenic stress (in general).
Any state that pushes the body to burn fat and make ketones (fasting, illness) can trigger a crisis. PubMedFasting or missed feeds.
Going many hours without food in infants and toddlers is a classic trigger. babysfirsttest.orgInfections (fever, diarrhea, vomiting).
Illness raises energy needs and reduces intake, so ketones surge and acids accumulate. babysfirsttest.orgHigh-protein meals rich in isoleucine.
A large intake of protein can feed the blocked pathway and worsen metabolite load. KDHE KansasLow-carb or ketogenic patterns.
Low carbohydrate increases ketone production and can precipitate acidosis. Metabolic Support UKDehydration.
Dehydration concentrates acids and reduces kidney clearance of organic acids. babysfirsttest.orgSurgery or major physical stress.
Stress hormones and fasting around procedures create a ketotic state. PubMedRapid weight loss or prolonged exertion without carbs.
Both increase fat burning and ketone load. (Mechanism summarized under “ketogenic stress”.) PubMedPoor access to emergency dextrose during illness.
Delayed carbs prolong ketosis and acidosis during a crisis. OrphaInfancy and early childhood physiology.
Young children have low fasting reserves, making crises more likely at that age. PubMedUndiagnosed status.
Before diagnosis, routine illnesses repeatedly trigger severe attacks. PubMedIntercurrent hypermetabolic states (fever).
Fever increases energy needs and ketone generation. babysfirsttest.orgGastroenteritis with poor intake.
Vomiting/diarrhea reduce carbs and fluids and raise risk of crisis. babysfirsttest.orgProlonged overnight fasts in toddlers.
Long sleep without feeds can be enough to start ketosis. babysfirsttest.orgHigh fat load during illness without carbs.
If carbs are low, fat is burned, ketones rise, and symptoms worsen. PubMedResidual enzyme differences.
People with very low or no K⁺-activated T2 activity tend to be more crisis-prone. NatureGenetic variability across populations.
Different ACAT1 variants exist worldwide; severity can vary case-by-case. Wiley Online Library
Symptoms and signs
Tiredness and sleepiness.
Children may sleep more, look weak, or be hard to wake during a crisis. babysfirsttest.orgVomiting and poor appetite.
Food refusal and repeated vomiting are common early signs. babysfirsttest.orgFast or deep breathing (Kussmaul).
The body tries to blow off acid by breathing faster and deeper. PMCDehydration.
Dry mouth, less urine, sunken eyes can appear, especially with vomiting. babysfirsttest.orgFever or illness.
Many attacks start with a simple infection. babysfirsttest.orgConfusion or unusual behavior.
Acidosis affects the brain; children may seem “not themselves.” PubMedSeizures.
Seizures can occur during severe crises. babysfirsttest.orgComa in severe cases.
If untreated, a crisis can progress to coma. babysfirsttest.orgBreath with fruity odor.
High ketones can cause a sweet or acetone smell. rareportal.org.auLow muscle tone or stiffness later on.
Some children develop hypotonia or movement problems after crises. BioMed CentralDevelopmental delay in some.
Milestones can be slower if crises are frequent or severe. BioMed CentralMetabolic “stroke” symptoms.
Sudden weakness, movement changes, or abnormal MRI can appear with a crisis. PMCRapid breathing and shortness of breath.
This is part of the acid-washout response. rareportal.org.auPossible heart rhythm issues over time.
Prolonged QT has been reported; monitoring is wise. KDHE KansasWide range of severity.
Some people remain well with prevention; others have repeated serious crises. BioMed Central
Diagnostic tests
A) Physical exam
General look and mental status.
Check for lethargy, confusion, or coma during illness—common in T2 crises. babysfirsttest.orgBreathing pattern.
Deep, rapid breathing (Kussmaul) suggests metabolic acidosis. PMCHydration status.
Dry mucosa, weak pulses, poor skin turgor often accompany vomiting. babysfirsttest.orgNeurologic exam.
Look for seizures, abnormal tone, dystonia, or signs of “metabolic stroke.” PMCGrowth and baseline development.
Check weight/height and milestones; repeated crises can affect both. BioMed Central
B) Manual / bedside tests
Finger-stick glucose.
Hypoglycemia or sometimes hyperglycemia can occur in a crisis; quick glucose is essential. J Pediatr Endocrinol DiabetesUrine ketone dipstick.
A rapid check that often shows high ketones during attacks. (Formal labs confirm.) J Pediatr Endocrinol DiabetesPoint-of-care blood gas.
Bedside venous/arterial blood gas shows low pH / low bicarbonate in metabolic acidosis. NCBI
C) Laboratory & pathological tests
Serum electrolytes with anion gap.
A high anion gap supports organic acidemia; calculate and trend during care. Life in the Fast Lane • LITFLComprehensive metabolic panel and lactate.
Helps grade acidosis and rule out other causes of high-gap acidosis. AJKDPlasma ammonia.
Hyperammonemia can accompany severe crises and influences ICU management. Çocuk MetabolizmaPlasma acylcarnitine profile (MS/MS).
Typical markers are C5-OH (2-methyl-3-hydroxybutyrylcarnitine) and C5:1 (tiglylcarnitine); some patients also show C4-OH. PMC+2Wadsworth Center+2Urine organic acids (GC-MS).
Key findings are 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate (often unstable), and tiglylglycine—a classic triad. PMC+1Repeat urine/blood during wellness and during crisis.
Patterns can fluctuate; some newborns have normal screens, so clinical testing remains important. PubMedGenetic testing of the ACAT1 gene.
Identifies causative variants and confirms diagnosis; also helps with family counseling. Groningen Research PortalFibroblast enzyme assay (specialized).
Measures potassium-activated acetoacetyl-CoA thiolase activity; in T2 deficiency this activity is absent/low. NatureCarnitine levels.
Secondary carnitine changes may appear; some centers monitor for management. Dir JournalNewborn screening review.
Many programs flag C5-OH and C5:1 elevations; however false-negatives occur, so do not rely on NBS alone when a child is ill. Wadsworth Center+1
D) Electrodiagnostic tests
EEG when seizures or altered awareness occur.
EEG helps confirm and manage seizure activity during decompensation; it does not prove T2 deficiency by itself. babysfirsttest.orgECG / rhythm monitoring.
Useful in sick patients; prolonged QT has been reported in individuals with BKT deficiency, so periodic cardiac review is reasonable. KDHE Kansas
E) Imaging tests (supportive)
- Brain MRI (and sometimes CT) can show basal ganglia (striatal) involvement or even broader lesions during or after crises; these changes support the diagnosis in context and help anticipate neurologic risks. MR spectroscopy and NMR-based urinalysis are research/adjunct tools that can detect related metabolites. PMC+2PubMed+2
Non-pharmacological treatments (therapies & others)
Sick-day “high-carb, no-fasting” plan
Description: At the first sign of illness (fever, vomiting, diarrhea, poor intake), give frequent carbohydrate-rich fluids or oral rehydration with glucose polymers; if oral intake is unreliable, go to hospital for IV dextrose to block catabolism. Avoid prolonged fasting at any age. Families should keep a written emergency letter.
Purpose: Prevent the body from breaking down fat and protein that worsens ketoacidosis.
Mechanism: Extra glucose raises insulin and suppresses lipolysis/ketogenesis and proteolysis, reducing production of toxic isoleucine intermediates and ketone bodies. Orpha+1Illness-trigger avoidance & early fever management
Description: Infections commonly trigger decompensation. Use prompt hydration, antipyretics as directed by clinicians, and early medical review for fever, cough, or GI illness. Keep vaccinations up to date.
Purpose: Cut the catabolic load and stress hormones that accelerate ketone and organic acid buildup.
Mechanism: Reducing fever and dehydration decreases counter-regulatory hormones and metabolic flux through impaired pathways. Newborn ScreeningRoutine day-to-day frequent meals/snacks
Description: Children need regular carbohydrate-containing meals and snacks, including bedtime snacks; adolescents/adults should avoid long fasting (e.g., overnight fasting without snack).
Purpose: Prevent overnight or inter-meal catabolism.
Mechanism: Steady glucose availability limits ketogenesis and isoleucine catabolism. OrphaMild, individualized protein moderation (especially in early childhood)
Description: Under dietitian supervision, total protein is kept appropriate for age but may be modestly moderated to reduce isoleucine load without risking malnutrition; never restrict without specialist guidance.
Purpose: Limit upstream isoleucine metabolites that accumulate in ACAT1 deficiency.
Mechanism: Lower substrate flow through the blocked step decreases 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, and tiglylglycine formation. Orpha+1Avoid deliberate ketogenic or very high-fat diets
Description: Ketogenic diets can provoke ketoacidosis; families should inform all clinicians to avoid ketogenic prescriptions.
Purpose: Reduce ketone overproduction.
Mechanism: Less fat-driven ketogenesis → less acid load in a ketolysis/ketogenesis defect. OrphaEarly IV glucose during vomiting or poor intake
Description: In emergency care, give dextrose-containing IV fluids promptly (concentration and rate per age/severity).
Purpose: Halt catabolism when oral intake fails.
Mechanism: IV glucose rapidly increases insulin and suppresses fat/protein breakdown. Metabolic Support UKTargeted acid–base monitoring
Description: During crises, check blood gas, anion gap, lactate, electrolytes frequently; treat metabolic acidosis per protocol.
Purpose: Detect and correct life-threatening acidosis early.
Mechanism: Guided correction reduces acidemia-related organ dysfunction. BiomedresAmmonia monitoring and escalation plan
Description: Measure plasma ammonia during decompensation; if elevated, follow hyperammonemia pathways (glucose, nitrogen scavengers, dialysis if refractory).
Purpose: Prevent encephalopathy.
Mechanism: Lowering ammonia decreases neurotoxicity. ScienceDirectEmergency dialysis in refractory crises
Description: Hemodialysis or peritoneal dialysis may be used for severe, treatment-resistant acidosis or hyperammonemia.
Purpose: Rapidly remove acids and ammonia when medical therapy fails.
Mechanism: Extracorporeal clearance of toxic metabolites. Journal of Pediatric ResearchRespiratory support when indicated
Description: Severe acidosis may cause Kussmaul breathing or fatigue; provide oxygen, non-invasive support, or intubation per ICU protocols.
Purpose: Maintain gas exchange while metabolic therapy works.
Mechanism: Stabilizes ventilation and oxygenation during crisis. Metabolic Support UKHome education & emergency letter
Description: Families should carry a metabolic emergency letter explaining ACAT1 deficiency and hospital actions (IV dextrose, acid–base checks).
Purpose: Speed correct treatment at first medical contact.
Mechanism: Reduces delays that allow worsening catabolism. Newborn ScreeningRegistered dietitian follow-up
Description: Regular growth, nutrition, and biochemical review; adjust protein/carbohydrate plans with age.
Purpose: Prevent under-nutrition while minimizing triggers.
Mechanism: Optimizes substrate supply and avoids deficiencies. OrphaNewborn screening integration and confirmatory testing
Description: Many programs flag BKT on acylcarnitines; confirm by urine organic acids and ACAT1 sequencing.
Purpose: Enable pre-symptomatic management and education.
Mechanism: Early diagnosis prevents first decompensation. Newborn ScreeningHydration strategies
Description: Oral rehydration at home during mild illness; IV isotonic fluids when dehydrated.
Purpose: Restore perfusion and support renal clearance of acids.
Mechanism: Improves renal excretion of organic acids and supports glucose delivery. Metabolic Support UKStructured return-to-feeding after crisis
Description: Gradual re-introduction of feeds with adequate carbs and age-appropriate protein, under team guidance.
Purpose: Prevent rebound catabolism.
Mechanism: Maintains anabolic state while acids clear. PMCSchool/daycare care plan
Description: Provide written instructions for snacks, illness calls, and when to seek medical help.
Purpose: Reduce accidental fasting and delays.
Mechanism: Timely carbs and care during day prevent crises. Newborn ScreeningMedication reconciliation to avoid prolonged fasting for procedures
Description: For surgery or imaging, plan IV dextrose during NPO periods.
Purpose: Prevent catabolic stress in hospital.
Mechanism: Continuous glucose blocks ketogenesis. OrphaGenetic counseling
Description: Discuss autosomal recessive inheritance, carrier testing for parents/siblings, and future pregnancy planning.
Purpose: Inform family risk and newborn planning.
Mechanism: Enables early testing and treatment pathways. MedlinePlusMetabolic clinic registry and periodic review
Description: Join specialized clinics/registries to keep care updated and learn about trials.
Purpose: Improve long-term outcomes.
Mechanism: Access to expertise and updated protocols. BioMed CentralPsychosocial support
Description: Provide caregiver education, stress management, and social work support; teach symptom recognition.
Purpose: Improve adherence and early response to illness.
Mechanism: Empowered families act promptly to prevent crises. Newborn Screening
Drug treatments
Important note: No medicine “fixes” the enzyme block; drugs below are supportive during crises or for prevention as guided by a metabolic specialist.
Levocarnitine (CARNITOR®)
Class: Carnitine replacement. Dose/Time: Typical oral 50–100 mg/kg/day in divided doses (doses individualized); IV formulations available. Purpose: Replenish free carnitine, facilitate excretion of acyl groups as acylcarnitines, support fatty-acid transport balance. Mechanism: Restores carnitine pool depleted by organic acids; may reduce toxic acyl-CoA accumulation. Side effects: GI upset, fishy odor, rare seizures at high doses. FDA Access Data+1Dextrose Injection (5–50%)
Class: Parenteral carbohydrate. Dose/Time: Concentration/rate per age/severity; examples include 10% in maintenance infusions for pediatrics; 25–50% for bolus in select indications per label/clinical protocols. Purpose: Rapid anti-catabolic glucose supply. Mechanism: Increases insulin, suppresses ketogenesis/proteolysis. Side effects: Hyperglycemia, vein irritation with high osmolarity, electrolyte shifts. FDA Access Data+1Sodium Bicarbonate Injection
Class: Systemic alkalinizer. Dose/Time: Titrated to blood gas; used for significant metabolic acidosis in monitored settings. Purpose: Correct severe acidosis. Mechanism: Bicarbonate buffers hydrogen ions, raising blood pH. Side effects: Hypernatremia, volume overload, paradoxical CNS pH changes if overused. U.S. Food and Drug Administration+1Sodium citrate–citric acid (e.g., Bicitra®)
Class: Oral alkalinizing solution. Dose/Time: Per label and clinician guidance. Purpose: Maintain serum/urine alkalinity in milder acidosis or between crises. Mechanism: Metabolized to bicarbonate equivalents. Side effects: GI discomfort, sodium load concerns. DailyMedAMMONUL® (sodium phenylacetate/sodium benzoate)
Class: Nitrogen-scavenging agent. Dose/Time: IV per label protocol for hyperammonemia (usually in urea-cycle disorders but can be used adjunctively if ammonia high). Purpose: Reduce ammonia during decompensation. Mechanism: Conjugates with glutamine/glycine to form excretable products, lowering ammonia. Side effects: Nausea, acidosis risk, sodium load; requires central line. FDA Access Data+10.9% Sodium Chloride / balanced crystalloids
Class: IV fluids. Dose/Time: Per dehydration severity. Purpose: Restore perfusion and support renal clearance. Mechanism: Volume expansion → improved renal organic acid excretion. Side effects: Fluid overload, electrolyte shifts. (Label references vary by manufacturer; used as standard of care alongside dextrose.) Metabolic Support UKOndansetron (ZOFRAN®)
Class: 5-HT3 antiemetic. Dose/Time: Weight-based IV/PO per label; used during vomiting to maintain oral intake. Purpose: Control vomiting to allow carb hydration and prevent emergency escalation. Mechanism: Blocks serotonin 5-HT3 receptors in gut/CTZ. Side effects: Headache, constipation, QT prolongation risk; contraindicated with apomorphine. FDA Access Data+1Acetaminophen (paracetamol)
Class: Antipyretic/analgesic. Dose/Time: Pediatric/adult dosing per label. Purpose: Reduce fever/catabolic stress. Mechanism: Central COX inhibition to reduce fever. Side effects: Hepatotoxicity in overdose (use exact dosing). (Use FDA label for brand formulations as available in your country.) Newborn ScreeningAntibiotics when infection is documented/suspected (e.g., amoxicillin–clavulanate)
Class: Antibacterial. Dose/Time: Per infection and label. Purpose: Treat triggers that precipitate metabolic crisis. Mechanism: Kills or inhibits pathogens, shortening catabolic illness. Side effects: GI upset, allergy, diarrhea. (Use specific FDA label for chosen agent.) Newborn ScreeningProton-pump inhibitor or H2 blocker (as indicated)
Class: Acid suppression. Purpose: Protect GI mucosa during severe vomiting/illness to support feeding tolerance. Mechanism: Reduces gastric acid. Side effects: Headache, diarrhea; use only if indicated. (Use specific FDA label where relevant.) Metabolic Support UKElectrolyte repletion agents (e.g., potassium, phosphate) per labs
Class: Electrolyte replacement. Purpose: Correct deficits from vomiting/IV therapy. Mechanism: Restores cellular function and buffering capacity. Side effects: Arrhythmias with improper dosing; give under monitoring. BiomedresThiamine (if differential includes other organic acidemias or malnutrition)
Class: Vitamin cofactor. Purpose: Empiric use in some centers during unexplained acidosis while workup proceeds; not disease-specific for ACAT1 deficiency. Mechanism: Supports pyruvate dehydrogenase and other enzymes. Side effects: Rare hypersensitivity with IV use. Wiley Online LibraryInsulin (only if hyperglycemia develops during high-dextrose therapy)
Class: Hormone. Purpose: Control glucose while maintaining anti-catabolic dextrose infusion. Mechanism: Promotes glucose uptake; anti-catabolic. Side effects: Hypoglycemia risk—careful titration required. FDA Access DataMultivitamin/trace elements in prolonged illness/TPN
Class: Nutritional support. Purpose: Prevent deficiencies during prolonged NPO/TPN. Mechanism: Provides essential cofactors. Side effects: Minimal when appropriately dosed. Metabolic Support UKAnalgesics for pain as appropriate
Class: Non-opioid/short-course opioid per indication. Purpose: Comfort, reduce stress hormones. Mechanism: Pain control lowers catabolic drive. Side effects: Drug-specific; avoid NSAIDs if dehydration/renal risk. Metabolic Support UKAnticonvulsants if seizures occur (e.g., levetiracetam)
Class: Antiepileptic. Purpose: Treat acute seizures during decompensation. Mechanism: Reduces neuronal hyperexcitability. Side effects: Somnolence, mood changes; choose agent per clinician. PMCBicarbonate-based oral maintenance (if recurrent mild acidosis)
Class: Oral alkalinizer (bicarbonate/citrate). Purpose: Maintain pH between episodes as directed. Mechanism: Buffers acid load. Side effects: Sodium load; monitor. DailyMedAntidiarrheals/antiemetics adjuncts (clinician-directed)
Class: Symptom control. Purpose: Maintain hydration/nutrition. Mechanism: Reduces GI losses to support carb intake. Side effects: Agent-specific; avoid in red-flag scenarios. FDA Access DataParenteral nutrition (short-term if enteral impossible)
Class: Nutritional therapy. Purpose: Provide calories when GI rest needed. Mechanism: IV macronutrients prevent catabolism. Side effects: Line infection, metabolic complications—specialist oversight required. FDA Access DataDialysis solutions/anticoagulation per modality
Class: Extracorporeal therapy adjuncts. Purpose: Enable toxin removal when dialysis is used. Mechanism: Solute clearance and fluid control. Side effects: Modality-specific. Journal of Pediatric Research
Clinical reality check: The core ACAT1-specific medicines most often cited are dextrose, bicarbonate/citrate, and levocarnitine, with nitrogen scavengers reserved for significant hyperammonemia; the rest are supportive/adjunctive and used as clinically indicated. Metabolic Support UK+1
Dietary molecular supplements
Oral glucose polymers (maltodextrin solutions) — convenient carbohydrate during illness to suppress catabolism; dose per dietitian. Mechanism: Steady glucose → anti-ketogenic. Orpha
Levocarnitine (oral) — supports carnitine pool and acylcarnitine excretion (see drug section for dosing). Mechanism: Shuttles acyl groups for excretion. FDA Access Data
Electrolyte-glucose oral rehydration — replaces salts and carbs to prevent dehydration and ketosis. Mechanism: Sodium–glucose cotransport improves hydration and provides carbs. Metabolic Support UK
Sodium citrate/citric acid — oral alkalinization between episodes as prescribed. Mechanism: Metabolized to bicarbonate equivalents. DailyMed
Age-appropriate protein modules (as needed) — maintain growth while moderating isoleucine; not zero-protein; exact grams by dietitian. Mechanism: Balanced amino acid supply without excess substrate load. Orpha
Standard multivitamin/mineral — prevents deficiency during chronic dietary adjustments. Mechanism: Ensures cofactors for energy metabolism. Metabolic Support UK
Vitamin D and calcium (per local guidelines) — bone health during chronic dietary management. Mechanism: Supports skeletal metabolism. Metabolic Support UK
Zinc (if deficient) — supports immune/repair functions; only with testing and guidance. Mechanism: Cofactor for enzymes and mucosal integrity. Metabolic Support UK
Folate/B-complex when dietary intake is marginal — general metabolic support; not ACAT1-specific. Mechanism: Cofactors for one-carbon/energy pathways. Wiley Online Library
Fiber/soluble fiber during recovery — improves GI tolerance and glycemic steadiness for regular carbs. Mechanism: Slows absorption and stabilizes energy supply. Metabolic Support UK
Immunity booster / regenerative / stem-cell drugs
There are no approved “immunity-booster,” “regenerative,” or stem-cell drugs for ACAT1 deficiency, and none are part of standard care. Management remains supportive: prevent catabolism, give glucose, correct acidosis, supplement carnitine, and treat triggers; outcomes are generally favorable with this approach. Using unproven agents can be harmful and delay effective care. If you see claims online about stem cells, discuss them with a metabolic specialist and check for registered clinical trials instead. BioMed Central+1
Procedures / surgeries
Peripheral/central IV access placement — to deliver dextrose, bicarbonate, and medications quickly during crises; central lines are used when high-osmolar or AMMONUL infusions are needed. FDA Access Data
Endotracheal intubation & mechanical ventilation — for severe respiratory fatigue or depressed consciousness during acidosis; supports breathing while metabolic issues are corrected. Metabolic Support UK
Hemodialysis — rapid clearance of ammonia and organic acids when medical therapy fails or when hyperammonemia is severe. ScienceDirect
Peritoneal dialysis — alternative dialysis modality when hemodialysis is not feasible, used in some pediatric reports. Journal of Pediatric Research
Feeding tube (temporary) during prolonged recovery — ensures reliable carbohydrate intake and medication delivery if oral intake is unsafe. Metabolic Support UK
Preventions
Never skip meals; avoid long fasting (snacks, bedtime snack). Orpha
Sick-day plan at home and in hospital (carb-first, early ED visit if vomiting). Orpha
Up-to-date vaccinations to reduce infection triggers. Newborn Screening
Written emergency letter carried at all times. Newborn Screening
Hydration habits (extra fluids during heat/fever). Metabolic Support UK
Dietitian-guided protein moderation in early childhood. Orpha
Avoid ketogenic/very high-fat diets unless a specialist explicitly directs otherwise (generally avoided). Orpha
Rapid treatment of infections (seek care early). Newborn Screening
Procedure planning (IV dextrose during NPO). Orpha
Regular metabolic clinic follow-up with labs and growth checks. BioMed Central
When to see doctors (immediately)
Seek urgent care for vomiting, refusal to drink/eat, fever, unusual sleepiness, fast/labored breathing, confusion, seizures, or signs of dehydration—especially in infants/young children. Tell the team about ACAT1 deficiency and show your emergency letter so they start IV dextrose and check acid–base status and ammonia without delay. Early treatment is key to preventing coma or neurologic injury. Newborn Screening+1
What to eat
Eat/do:
Regular meals/snacks with carbohydrates (grains, fruits, milk) to prevent fasting. Orpha
Illness carbs early (oral rehydration/glucose polymers) at first symptoms. Orpha
Adequate fluids daily and more during fever. Metabolic Support UK
Protein in age-appropriate amounts under dietitian guidance. Orpha
Multivitamin/mineral as advised. Metabolic Support UK
Avoid/limit:
- Long fasting/meal skipping (including overnight without snack). Orpha
- Deliberately ketogenic/high-fat diets. Orpha
- Excess protein loads beyond plan. Orpha
- Unsupervised supplements promising “detox” or “regeneration.” BioMed Central
- Delays in care during illness—go early. Newborn Screening
Frequently asked questions
Is ACAT1 (beta-ketothiolase) deficiency curable?
No. There’s no enzyme-replacement today; care prevents and treats ketoacidosis so children can grow and develop. Labcorp Women’s Health+1Why are illnesses so risky?
Illness raises stress hormones and reduces intake, pushing the body to burn fat/protein, which overloads impaired pathways and causes acidosis. OrphaWhat does carnitine do here?
It replenishes the carnitine pool and helps remove toxic acyl groups as acylcarnitines; many centers give it during and between crises. FDA Access DataDo I always need IV glucose when sick?
Start carbs early at home; if vomiting or intake is poor, IV dextrose in hospital is recommended to block catabolism. Metabolic Support UKIs protein bad?
No—adequate protein is needed for growth. A mild, individualized moderation may help in early years; never restrict without a metabolic dietitian. OrphaWhat tests confirm the diagnosis?
Urine organic acids (elevated 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, tiglylglycine) and ACAT1 gene testing confirm BKT. OrphaWhy check ammonia?
Ammonia can be elevated during crises; treating it promptly prevents brain injury. ScienceDirectWhat is the long-term outlook?
Often favorable when families use sick-day plans and urgent dextrose/acid–base correction. PMCAre ketogenic diets helpful?
No; they are generally contraindicated in ACAT1 deficiency because they can precipitate ketoacidosis. OrphaCan adults be diagnosed?
Yes—some cases are recognized later, but most present in infancy/toddler years. MedlinePlusWhat about “potassium-stimulated” testing?
Older reports sometimes described potassium-linked changes in urinary metabolite excretion; current practice relies on urine organic acids and ACAT1 genetics. OrphaDo we need an emergency letter?
Yes—this speeds correct IV dextrose and monitoring in any ER. Newborn ScreeningWhich drugs are the most important during a crisis?
Dextrose, bicarbonate/alkalinizers, and levocarnitine; add nitrogen scavengers only if ammonia is high. FDA Access Data+2U.S. Food and Drug Administration+2Are stem-cell or “regenerative” therapies available?
No approved therapies exist; management is supportive. Be cautious about unproven claims. BioMed CentralWhere can I read more?
See Orphanet, HRSA Newborn Screening guidance, and systematic reviews on MATD/BKT outcomes and care. Orpha+2Newborn Screening+2
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: October 23, 2025.
