LCHADD/TFP Deficiency
Description
Diagnosis Coding
E71.310, Long chain/very long chain acyl CoA dehydrogenase deficiency
ICD-10 for LCHADD and VLCADD (icd10data.com) provides further coding details.
Description
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a disorder of fatty acid oxidation. During times of fasting, the body uses fat as a major source of energy. Fats are catabolized through a process called beta-oxidation. The overall reaction involves several different enzymes which break down very-long chain fats to long-chain fats, long-chain fats to medium-chain fats, eventually resulting in ketone bodies and acetyl-CoA. The former are used directly for energy and the latter enter the Kreb cycle to generate ATP and reducing equivalents.Long-chain fatty acids are broken down by the trifunctional protein (TFP) after initial metabolism by very-long chain acyl CoA dehydrogenase. This protein catalyzes 3 steps (for which it got its name) in the beta-oxidation of fatty acids, including the hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity. Mutations that completely abolish the function of the protein cause TFP deficiency. LCHADD is caused by mutations that allow the reaction to start but not to be completed.
LCHADD and TFP deficiency cause cellular damage from accumulation of 3-OH-fatty acids, impaired energy production from longer chain fatty acids, and consequent hypoglycemic crises during prolonged fasting or increased energy demands, such as fever or other stress. Treatment mainly involves avoiding fasting, following strict dietary recommendations, and using supplements as needed.
Prevalence
A German study indicates a prevalence of 1:250,000 for LCHADD. [Schulze: 2003] The incidence of LCHADD in the United States is approximately 1:363,738. [Therrell: 2014]Genetics
LCHADD and TFP deficiency are inherited in an autosomal recessive manner. TFP is formed by 2 subunits (alpha and beta) encoded by 2 different genes (HADA and HADB) located on the same chromosome (2p23). TFP deficiency can be caused either by mutations in the alpha (HADA gene) or beta subunit (HADB gene). LCHADD is caused by specific missense mutations in the alpha subunit that allow the reaction to start but not to be completed.Prognosis
Prognosis varies depending on whether there is LCHADD alone or TFP deficiency. Symptoms (mild to severe) may begin at birth or take a few years to present. If LCHADD is treated prior to hypoglycemic crises, the child’s intelligence is likely to be normal; progression of peripheral neuropathy and retinitis pigmentosa can occur. Without treatment, hypoglycemic episodes may lead to developmental delay and neurologic impairment. Cardiomyopathy and/or hepatic failure may result in death. Pigmentary retinopathy develops with time. Neuropathy is more frequent and usually occurs earlier in patients with TFP deficiency. Symptoms, whether mild or severe, may begin anytime between birth and 3 years of age. All patients have exercise intolerance and develop myoglobinuria and muscle pain with strenuous exercise.Roles Of The Medical Home
The goal of treatment is to avoid progression of the disease and acute decompensations brought about by illness, fasting, and dehydration. Although management of the child with LCHADD will be a collaboration with metabolic genetics, the medical home clinician is crucial for early management of illnesses that may lead to decompensation. In the event of acute decompensation, the cause should be identified and treated if possible. Oral feedings should be restarted as soon as possible.IV glucose is necessary during illness and dehydration, and the medical home clinician should ensure that a plan is in place for such episodes. The usual treatment is the administration of glucose 10% with adequate salts (one quarter or one half normal saline - depending on age and weight - with 20 mEq/L of potassium chloride) at 1.5-twice maintenance, keeping in mind that this treatment does not provide all the calories that the child needs.
LCHADD/TFP Deficiency has information for medical home clinicians about the response to a positive newborn screen. The LCHADD Acute Illness Protocol (New England Consortium of Metabolic Programs) is a helpful guideline for health care professionals treating the sick infant or child who has previously been diagnosed with LCHADD.
Helpful Articles
De Biase I, Viau KS, Liu A, Yuzyuk T, Botto LD, Pasquali M, Longo N.
Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA
Dehydrogenase Deficiency.
JIMD Rep.
2017;31:63-71.
PubMed abstract / Full Text
Vockley J, Burton B, Berry GT, Longo N, Phillips J, Sanchez-Valle A, Tanpaiboon P, Grunewald S, Murphy E, Humphrey R, Mayhew
J, Bowden A, Zhang L, Cataldo J, Marsden DL, Kakkis E.
UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following
24weeks of treatment.
Mol Genet Metab.
2017;120(4):370-377.
PubMed abstract
Wilcken B.
Fatty acid oxidation disorders: outcome and long-term prognosis.
J Inherit Metab Dis.
2010.
PubMed abstract
Gillingham MB, Purnell JQ, Jordan J, Stadler D, Haqq AM, Harding CO.
Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA
dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency.
Mol Genet Metab.
2007;90(1):64-9.
PubMed abstract / Full Text
Clinical Assessment
Overview
Individuals with LCHADD or TFP deficiency can be diagnosed by newborn screening. In both cases, 3-OH-long-chain acylcarnitines (C16-OH being usually the most prominent) are elevated. The pattern is usually distinctive in LCHAD deficiency, whereas patients with TFP deficiency can have concomitant elevation of several other long-chain acylcarnitines (hydroxylated and non-hydroxylated) raising the possibility of other defects in long-chain fatty acid oxidation. When the screening test is positive, quantitative plasma acylcarnitine profile, urine organic acid analysis, free 3-OH-fatty acids, biochemical and molecular genetic testing in cultured fibroblasts derived from skin biopsy or white blood cells will be performed to differentiate between LCHADD, TFP, and other defects of long-chain fatty acid oxidation. In some patients, symptoms might occur before the results of newborn screening are back. These patients have a high mortality rate. [Sykut-Cegielska: 2010]Screening
For The Condition
Prenatal testing can be performed by DNA testing in cells obtained by amniocentesis or chorionic villous sampling (CVS). The newborn screening finding is elevated C16-OH +/- and C18:1-OH as determined by tandem mass spectrometry (MS/MS) with a sensitivity of 100% and a specificity of 100%. [Schulze: 2003]The American College of Medical Genetics endorses Confirmatory Algorithms for LCHAD and TFP Deficiency (ACMG) (
69 KB), which recommends obtaining plasma acylcarnitine profile and urine organic acids following abnormal screening results. The
plasma acylcarnitine profile is usually abnormal, with elevation of C16-OH and other hydroxyacylcarnitine species and other
long-chain acylcarnitines are usually increased. It is not possible to differentiate LCHADD from TFP deficiency based solely
on the acylcarnitine profile, although levels of C16-OH-carnitine are usually higher in LCHADD. Urine organic acids are usually
normal if the child is well compensated. LCHADD/TFP Deficiency has further information about the response to a positive newborn screen.
Presentations
There are 3 main ways that LCHAD/TFP deficiency may present, although clinical presentations occur in a spectrum of severity.- Infants may be identified by newborn screening before they show symptoms.
- Infants may present near birth and generally have a more severe form of the condition. Symptoms may begin anytime between
birth and 3 years, and may be mild or severe. Initial symptoms/signs may include:
- Poor feeding
- Vomiting
- Lethargy
- Hypotonia
- Hepatomegaly
- Cardiac insufficiency
- Cardiomyopathy
- Lab findings: elevated liver function tests, elevated CK, metabolic acidosis, lactic acidosis, hypoglycemia
- Some individuals may not present until they are a few years of age. These individuals may show progressive retinitis pigmentosa and neuropathy although generally they have a milder form of LCHAD/TFP deficiency.
- Hepatic disease
- Cardiomyopathy
- Cardiac conduction defects (arrhythmia)
- Peripheral neuropathy
- Pigmentary retinopathy
- Rhabdomyolysis/myopathy
Diagnostic Criteria
DNA testing usually targets the common mutations causing LCHADD in the HADHA gene. If at least 1 copy of this mutation is identified, the patient likely has LCHADD. If this mutation is not present, both the HADHA and HADHB gene should be sequenced. Diagnosis is confirmed if 2 known pathogenic variants are identified. If only one such variant is identified, functional studies in fibroblasts (enzyme assay, acylcarnitine profiling, fatty acid oxidation probe) can be obtained.Differential Diagnosis
The infant form may be confused with other rare forms of cardiomyopathy, including glycogen storage disease type 2 (Pompe disease), VLCAD and multiple acyl-CoA dehydrogenase deficiency, and other carnitine disorders, such as carnitine-acylarnitine translocase deficiency, carnitine palmitoyltransferase II (CPT II, neonatal form) deficiency, and carnitine uptake disorder. These would be distinguished by biochemical testing.Nonketotic hypoglycemia with hepatomegaly has a large differential diagnosis including:
- Other fatty acid oxidation disorders: These include deficiency of medium chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, carnitine palmitoyl transferase I, carnitine-acylcarnitine translocase, and carnitine transporter. Important clinical features that might help differentiate LCHADD from the other fatty acid oxidation disorders include the presence of cardiomyopathy and/or rhabdomyolysis (seen in several, but not all of the other disorders) and different metabolites in acylcarnitine and urine organic acid profiles (this latter is abnormal only if collected during an acute crisis).
- Ketogenesis defects: The ketogenesis defects often present within the first few days of life, although the pattern of presentation in later childhood may be very similar to that of LCHADD. Vomiting, decreased sensorium, and hepatomegaly are also presenting symptoms. Although hypoketotic hypoglycemia and sometimes hyperammonemia are biochemical features, severe ketoacidosis is the rule.
- Organic acidurias: These can usually be diagnosed by urine organic acids and plasma acylcarnitine profile.
- Respiratory chain defects: These are variable in their presentation with a variety of symptoms. Biochemically, affected individuals have lactic acidosis and ketonemia (often paradoxical - increased ketones after eating). Diagnosis is difficult and muscle biopsy is often necessary. Cardiomyopathy can be seen in these conditions, but hypoglycemia is not usually seen except as a result of liver involvement (mitochondrial DNA depletions syndromes).
- Carbohydrate metabolism defects: These may present with hypoglycemia, significant lactic acidosis, +/- ketosis, and hepatomegaly. Acylcarnitine profile and urine organic acid profile will be helpful in differentiating these disorders from LCHADD. Patients are usually diagnosed in childhood.
Comorbid Conditions
Comorbid conditions include:- Retinitis pigmentosa (RP): This is a genetic eye disorder. In this condition, progressive retinal damage occurs, usually affecting the rod cells of the retina, causing problems with night and peripheral vision, although the cone cells, affecting central vision, may also be affected. There is no treatment for this condition currently. Retinitis pigmentosa (MedlinePlus) has information about symptoms, exams, and tests.
- Neuropathy: The neuropathy affecting individuals with LCHAD/TFP deficiency has not been well characterized. In case reports, the neuropathy appears to affect the axons of both motor and sensory nerves. [Tein: 1999] Individuals with this condition might present with decreased patellar and ankle reflexes and decreased sensation in their feet. It is diagnosed by nerve conduction velocity/electromyography (NCV/EMG) if suspected.
- Myopathy: The myopathy that may affect individuals with LCHAD/TFP deficiency is distinct from the neuropathy that may be associated with this condition. Individuals may present with proximal muscle weakness that may be due to bouts of rhabdomyolysis and myoglobulinuria associated with this disorder. NCV/EMG testing may be ordered if suspected. Although myopathy has been described in individuals with LCHAD/TFP deficiency, the time course and prognosis is not well understood. [Spiekerkoetter: 2009]
History & Examination
Pregnancy Or Perinatal History
HELLP (hemolysis, elevated liver enzymes, and low platelet count), acute fatty liver of pregnancy (AFLP) syndrome, and increased incidence of pre-eclampsia and eclampsia can be seen in mothers carrying a child with LCHAD or TFP deficiency. These complications can be life-threatening in the mother and lead to premature birth.Current And Past Medical History
Ask about recent illnesses and episodes of hypoglycemia. Ask about vision abnormalities. Ask about episodes of muscle pain and brown urine due to rhabdomyolysis.Physical Exam
General
The physical examination of a well child with LCHADD or TFP deficiency is usually without abnormality unless sequelae are present from a previous acute episode.Testing
Sensory Testing
Because of the potential for retinitis pigmentosa, visual acuity should be tested regularly.Laboratory Testing
Relevant laboratories can be found at Genetic Testing Resources for LCHADD (GeneTests).Other Testing
Nerve conduction velocity testing/electromyography (NCV/EMG) testing may be ordered if neuropathy is suspected.Subspecialist Collaborations & Other Resources
Newborn Screening Programs (see Services below for relevant providers)
Most individuals with LCHADD will be diagnosed through newborn screening.
Pediatric Metabolic Genetics (see Services below for relevant providers)
Refer for Initial consultation and ongoing collaboration if the child is affected. Periodic visits will be needed to review the condition, assess the diet, and evaluate if any metabolic testing is needed.
Nutrition, Metabolic (see Services below for relevant providers)
A dietician may work with the family to devise an optimal approach to dietary management.
Pediatric Cardiology (see Services below for relevant providers)
Children should have a baseline evaluation for cardiomypoathy and then periodic evaluation to detect cardiomyopathy.
Pediatric Ophthalmology (see Services below for relevant providers)
Children should be followed to detect and manage retinitis pigmentosa.
Treatment & Management
Pearls & Alerts
Fasting, dehydration, and illnessFasting, dehydration, and illness may lead to hypoglycemia. Children with LCHADD aren't able to break down fats for energy and low glucose due to these conditions may lead to an acute decompensation.
IV glucose is necessary during illness and dehydrationThe medical home clinician should ensure that a plan is in place for times of illness or dehydration. The usual treatment is the administration of glucose 10% with adequate salts (one quarter or one half normal saline - depending on age and weight - with 20 mEq/L of potassium chloride) at 1.5-twice maintenance, keeping in mind that this treatment does not provide all the calories that the child needs.
How should common problems be managed differently in children with LCHADD/TFP Deficiency?
Other
When surgeries or dental procedures are needed, the child will need specific IV fluids containing glucose (see emergency management) to be started when the child is unable to eat before the procedure and continued until the child is able to eat again.Systems
Nutrition/Growth/Bone
A diet that is low in fat and high in carbohydrates may be recommended for some individuals. Foods high in long-chain fatty acids may need to be avoided. Medium chain triglyceride (MCT) oil supplements, as they don't require the LCHAD enzyme for breakdown, are necessary at least in the first year of life to provide sufficient amounts of calories. The metabolic geneticist may prescribe docosahexanoic acid (DHA)/essential fatty acids supplements and L-carnitine supplementation at low doses (25 mg/kg per day) for carnitine deficiency. Cornstarch supplements are sometimes required in children with the childhood form of the disease.
Adolescents and adults with LCHADD may experience symptoms with exercise, particularly if they haven't had sufficient carbohydrates. Symptoms may include muscle aches, cramps, and rhabdomyolysis, which may manifest as brown or reddish urine. Teens should avoid heavy exercise and drink plenty of sugar-containing beverages even with normal exercise. If they have symptoms, they should seek treatment immediately that includes IV rehydration with glucose-containing fluids to prevent kidney damage from rhabdomyolysis.
When surgeries or dental procedures are needed, the child will need specific IV fluids containing glucose (see emergency management) to be started when the child is unable to eat before the procedure and that should be continued until the child is able to eat again.
Subspecialist Collaborations & Other Resources
Pediatric Metabolic Genetics (see Services below for relevant providers)
Periodic visits will be needed to help with dietary management and updates on new findings.
Nutrition, Metabolic (see Services below for relevant providers)
Refer to help review growth parameters and diet.
Eyes/Vision
Subspecialist Collaborations & Other Resources
Pediatric Ophthalmology (see Services below for relevant providers)
Periodic evaluation to detect and manage retinitis pigmentosa.
Development (general)
Subspecialist Collaborations & Other Resources
Developmental - Behavioral Pediatrics (see Services below for relevant providers)
Referral may be helpful to clarify developmental delays and help coordinate detailed evaluation and management.
Questions from Clinicians
How will my patient's family be affected?
Your patient's family will need to follow strict guidelines with regard to illness and dehydration, and may need medications, depending on the enzyme deficiency. Support groups may be helpful.
Issues Related to LCHADD/TFP Deficiency
Funding & Access to Care
Writing Letters of Medical NecessityResources
Information for Clinicians
Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency (GeneReviews)
Excellent review by Nancy D Leslie, MD including information about the clinical description, differential diagnoses, management,
genetic counseling, and molecular genetics.
LCHADD - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.
LCHADD (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University.
Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; American
Academy of Pediatrics.
Helpful Articles
De Biase I, Viau KS, Liu A, Yuzyuk T, Botto LD, Pasquali M, Longo N.
Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA
Dehydrogenase Deficiency.
JIMD Rep.
2017;31:63-71.
PubMed abstract / Full Text
Gillingham MB, Purnell JQ, Jordan J, Stadler D, Haqq AM, Harding CO.
Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA
dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency.
Mol Genet Metab.
2007;90(1):64-9.
PubMed abstract / Full Text
Vockley J, Burton B, Berry GT, Longo N, Phillips J, Sanchez-Valle A, Tanpaiboon P, Grunewald S, Murphy E, Humphrey R, Mayhew
J, Bowden A, Zhang L, Cataldo J, Marsden DL, Kakkis E.
UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following
24weeks of treatment.
Mol Genet Metab.
2017;120(4):370-377.
PubMed abstract
Wilcken B.
Fatty acid oxidation disorders: outcome and long-term prognosis.
J Inherit Metab Dis.
2010.
PubMed abstract
Clinical Tools
Algorithms/Care Processes
ACT Sheet for LCHADD (ACMG) ( 333 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Confirmatory Algorithms for LCHAD and TFP Deficiency (ACMG) ( 69 KB)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American
College of Medical Genetics.
LCHADD Acute Illness Protocol (New England Consortium of Metabolic Programs)
A guideline for health care professionals treating the sick infant or child who has previously been diagnosed with LCHADD;
developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and
Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.
Other
Emergency Protocol Information & Letter Samples (FOD)
Links to emergency care sample letters for MCADD, VLCADD, LCHADD, and unclassified FOD; International Fatty Oxidation Disorders
Support Group.
Information & Support for Families
Family Diagnosis Page
Information on the Web
LCHADD/TFP Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (Genetics Home Reference)
Excellent, detailed review of the condition for patients and families; sponsored by the U.S. National Library of Medicine.
Mitochondrial Trifunctional Protein Deficiency (Genetics Home Reference)
Excellent, detailed review of the condition for patients and families; sponsored by the U.S. National Library of Medicine.
Resources for LCHAD Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
National & Local Support
Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.
Services for Patients & Families Nationwide
Developmental - Behavioral Pediatrics
We currently have no nationwide Developmental - Behavioral Pediatrics service providers listed; search our Services database for related services or, if relevant for you, a state link above.
Newborn Screening Programs
We currently have no nationwide Newborn Screening Programs service providers listed; search our Services database for related services or, if relevant for you, a state link above.
Nutrition, Metabolic
We currently have no nationwide Nutrition, Metabolic service providers listed; search our Services database for related services or, if relevant for you, a state link above.
Pediatric Cardiology
We currently have no nationwide Pediatric Cardiology service providers listed; search our Services database for related services or, if relevant for you, a state link above.
Pediatric Metabolic Genetics
We currently have no nationwide Pediatric Metabolic Genetics service providers listed; search our Services database for related services or, if relevant for you, a state link above.
Pediatric Ophthalmology
We currently have no nationwide Pediatric Ophthalmology service providers listed; search our Services database for related services or, if relevant for you, a state link above.
For other services related to this condition, browse our Services categories or search our database.
Bibliography
De Biase I, Viau KS, Liu A, Yuzyuk T, Botto LD, Pasquali M, Longo N.
Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA
Dehydrogenase Deficiency.
JIMD Rep.
2017;31:63-71.
PubMed abstract / Full Text
Gillingham MB, Purnell JQ, Jordan J, Stadler D, Haqq AM, Harding CO.
Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA
dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency.
Mol Genet Metab.
2007;90(1):64-9.
PubMed abstract / Full Text
Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome,
and implications.
Pediatrics.
2003;111(6 Pt 1):1399-406.
PubMed abstract
Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner MR, Boehles H, Das A, Haase C, Hennermann JB, Karall D, de Klerk
H, Knerr I, Koch HG, Plecko B, Röschinger W, Schwab KO, Scheible D, Wijburg FA, Zschocke J, Mayatepek E, Wendel U.
Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop.
J Inherit Metab Dis.
2009;32(4):488-97.
PubMed abstract
Sykut-Cegielska J, Gradowska W, Piekutowska-Abramczuk D, Andresen BS, Olsen RK, Ołtarzewski M, Pronicki M, Pajdowska M, Bogdańska
A, Jabłońska E, Radomyska B, Kuśmierska K, Krajewska-Walasek M, Gregersen N, Pronicka E.
Urgent metabolic service improves survival in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency detected by symptomatic
identification and pilot newborn screening.
J Inherit Metab Dis.
2010.
PubMed abstract
Tein I, Vajsar J, MacMillan L, Sherwood WG.
Long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency neuropathy: response to cod liver oil.
Neurology.
1999;52(3):640-3.
PubMed abstract
Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions
for research agenda planning.
Mol Genet Metab.
2014;113(1-2):14-26.
PubMed abstract / Full Text
Vockley J, Burton B, Berry GT, Longo N, Phillips J, Sanchez-Valle A, Tanpaiboon P, Grunewald S, Murphy E, Humphrey R, Mayhew
J, Bowden A, Zhang L, Cataldo J, Marsden DL, Kakkis E.
UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following
24weeks of treatment.
Mol Genet Metab.
2017;120(4):370-377.
PubMed abstract
Wilcken B.
Fatty acid oxidation disorders: outcome and long-term prognosis.
J Inherit Metab Dis.
2010.
PubMed abstract