Short chain acyl CoA dehydrogenase (SCAD) is a mitochondrial enzyme responsible for cleaving fatty acids in the early stages of fatty acid oxidation, from which adenosine triphosphate (ATP) is generated for numerous metabolic functions [1] [2] [3] [4]. But in the absence of SCAD, this process fails to generate ATP and leads to accumulation of various cytotoxic compounds, such as ethylmalonic acid, butyryl-carnitine, and methylsuccinyl-CoA [1] [5]. Short chain acyl CoA dehydrogenase deficiency stems from autosomal recessive mutations of SCAD genes located on chromosome 12, and the clinical presentation may be diverse [6]. The majority of patients develop initial signs and symptoms in the first few years of life [7], but neonates, younger children, and adults have all been described as patients in the literature [1] [2]. The most common features of short chain acyl CoA dehydrogenase deficiency are hypotonia, muscle weakness, myopathy, failure to thrive, delays in mental and physical development, as well as the presence of metabolic acidosis and ketotic hypoglycemia [1] [2] [5] [7]. The clinical course is highly variable, ranging from mild, nonspecific and transient to severely debilitating and possibly life-threatening [1] [7]

• Developmental Delay

  In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. [ncbi.nlm.nih.gov]

  One of the eight children reported by Waisbren and co-workers ( 2008 ) showed developmental delay consisting of a language delay at the age of 2 years. [link.springer.com]

  In affected individuals manifestations include seizures, developmental delay (delayed sitting/walking and/or speech/social interaction), failure to grow with poor feeding, and usually muscle weakness and hypotonia. [orpha.net]

• Epilepsy

  Epilepsy in childhood often remains unexplained and patients with epilepsy related to SCADD may remain undiagnosed because studies for SCADD are often not performed. [ncbi.nlm.nih.gov]

  Developmental delay was by far the most frequently reported, followed by behavioral disorders, epilepsy, hypotonia, and hypoglycemia. [link.springer.com]

  High prevalence of short-chain acyl-CoA dehydrogenase deficiency in the Netherlands, but no association with epilepsy of unknown origin in childhood. Neuropediatrics. 2011 Feb;42(1):13-7. doi: 10.1055/s-0031-1275342. [ghr.nlm.nih.gov]

• HELLP Syndrome

  SCAD deficiency may be associated with maternal HELLP syndrome. [ncbi.nlm.nih.gov]

  His mother developed a hemolysis-elevated liver enzymes-low platelets (HELLP) syndrome while pregnant with the index patient. Results. [pediatrics.aappublications.org]

  Mothers with an LCHADD fetus often have HELLP syndrome (hemolysis, elevated liver function tests, and low platelet count) during pregnancy. [merckmanuals.com]

  Pediatr-Res. 2001 Jan; 49(1): 18-23 den-Boer,-M-E; Ijlst,-L; Wijburg,-F-A; Oostheim,-W; van-Werkhoven,-M-A; van-Pampus,-M-G; Heymans,-H-S; Wanders,-R-J Heterozygosity for the common LCHAD mutation (1528g>C) is not a major cause of HELLP syndrome and the [malattierare.regione.veneto.it]

  Keywords Developmental Delay Newborn Screening HELLP Syndrome Newborn Screening Program Mitochondrial Fatty Acid Oxidation These keywords were added by machine and not by the authors. [link.springer.com]

• Feeding Difficulties

  In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. [ncbi.nlm.nih.gov]

  Speech delay [ more ] 0000750 Episodic metabolic acidosis 0004911 Ethylmalonic aciduria 0003219 Facial palsy Bell's palsy 0010628 Failure to thrive Faltering weight Weight faltering [ more ] 0001508 Feeding difficulties in infancy 0008872 Flexion contracture [rarediseases.info.nih.gov]

  Feeding difficulties, insufficient breast milk, and/or increased stress during delivery may increase the risk of metabolic crisis in the first days of life, as we described in two cases mentioned earlier, before NBS is reported. [dovepress.com]

• Fatigue

  Infants affected by the disease may display episodes of vomiting, low blood sugar, and fatigue. These episodes can be fatal. Affected infants may have difficulty feeding and fail to grow at the expected rate. [counsyl.com]

  No ketogenic or low carb diet: I know for myself (heterozygous for one of the variants), I felt really terrible and fatigued when trying a low carb diet. Mouse studies show that a low-fat diet (or a ‘not high-fat diet’) may be helpful. [geneticlifehacks.com]

  Movement disorder; Seizure Weakness (65%) Severity: Usually mild; Occasionally severe or none Distribution: Proximal; Symmetric; Legs > Arms; Paraspinal Course: Increases with age Other muscle features Muscle atrophy: May be generalized Fatigue with [neuromuscular.wustl.edu]

• Vomiting

  […] or episodes of nausea, vomiting and shortness of breath in older children and adults. [thinkgenetic.com]

  We describe the case of a 23-year-old male patient who had growth and mental retardation, recurrent vomiting, fever and seizures since infancy. [ncbi.nlm.nih.gov]

  SCADD is usually diagnosed in infancy or early childhood, when the affected individual presents with symptoms such as vomiting, low blood sugar, lack of energy, and failure to thrive. [nxgenmdx.com]

  Patients have vomiting and lethargy that may progress rapidly to seizures, coma, and sometimes death (which can also appear as SIDS). During attacks, patients have hypoglycemia, hyperammonemia, and unexpectedly low urinary and serum ketones. [merckmanuals.com]

• Failure to Thrive

  As a result, patients present at an early age with muscle weakness, failure to thrive, developmental delay, hypotonia, seizures, and metabolic acidosis. [symptoma.com]

  In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. [ncbi.nlm.nih.gov]

  SCADD is usually diagnosed in infancy or early childhood, when the affected individual presents with symptoms such as vomiting, low blood sugar, lack of energy, and failure to thrive. [nxgenmdx.com]

  […] to gain weight and grow at the expected rate ( failure to thrive ). [rarediseases.info.nih.gov]

• Nausea

  […] who do have symptoms, these symptoms include problems eating, low muscle tone (they may be floppy), delays in development, vomiting, low energy (lethargy) and seizures in infants and muscle cramps or pain and difficulty with exercise or episodes of nausea [thinkgenetic.com]

  Some may experience periods of pain, nausea, and shortness of breath. It is thought that many cases are so mild that they are never diagnosed. SCAD deficiency belongs to a group of diseases known as fatty acid oxidation disorders. [counsyl.com]

  […] believe they said there were clear droplets viewed on biopsy, and somehow I had thought they were referring to glycogen that is non-stained when used with PAS). 7) Know that carnitine acyl-transferase-I is in the cytosol; CAS-II is in the mitochondria. 8) Nausea [forums.studentdoctor.net]

• Recurrent Vomiting

  We describe the case of a 23-year-old male patient who had growth and mental retardation, recurrent vomiting, fever and seizures since infancy. [ncbi.nlm.nih.gov]

  Recurrent vomiting and ethylmalonic aciduria associated with rare mutants of short-chain acyl-CoA dehydrogenase gene. J Inherit Metab Dis. 2003;26:37-42. Leonard JV, Dezateux C. [rarediseases.org]

  J Inherit Metab Dis 25(Suppl1):4 Google Scholar Seidel J, Streck S, Bellstedt K, Vianey-Saban C, Pedersen CB, Vockley J, Korall H, Roskos M, Deufel T, Trefz KF, Sewell AC, Kauf E, Zintl F, Lehnert W, Gregersen N (2003) Recurrent vomiting and ethylmalonic [link.springer.com]

• Hepatomegaly

  The index patient was born prematurely and had otherwise unexplained cholestasis and hepatomegaly during the first year of life. [ncbi.nlm.nih.gov]

  […] acylcarnitine esters, elevated urinary C6–C14 dicarboxylic acids Clinical features: In the VLCAD-C type, arrhythmia, hypertrophic cardiomyopathy, sudden death In the VLCAD-H type, recurrent hypoketotic hypoglycemia, encephalopathy, mild acidosis, mild hepatomegaly [merckmanuals.com]

  Background Information for Medium Chain Acyl-CoA Dehydrogenase Deficiency ( ACADM ) Sequencing: Characteristics: Limited mitochondrial fatty acid beta-oxidation leading to hypoglycemia, lethargy, seizures, hypoketotic dicarboxylic aciduria, vomiting, hepatomegaly [ltd.aruplab.com]

  […] infants Encephalopathy: Episodic; r/o Reyes syndrome Myopathy: Generalized weakness Cardiomyopathy Dilated Ventricular hypertrophy Heterozygous OCTN2 mutations: Predisposed to late-onset benign cardiac hypertrophy Cardiac failure may occur < 10 years Hepatomegaly [neuromuscular.wustl.edu]

• Muscle Weakness

  As a result, patients present at an early age with muscle weakness, failure to thrive, developmental delay, hypotonia, seizures, and metabolic acidosis. [symptoma.com]

  As a result, these fats are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy, hypoglycemia, and muscle weakness. [ghr.nlm.nih.gov]

  In affected individuals manifestations include seizures, developmental delay (delayed sitting/walking and/or speech/social interaction), failure to grow with poor feeding, and usually muscle weakness and hypotonia. [orpha.net]

  In affected individuals, the observed manifestations are convulsions, developmental delay (delay to sit and walk and to talk or maintain social interaction) and poor growth and poor nutrition as well as muscle weakness and hypotonia. [tellmegen.cl]

• Small Head

  head size, and behavior changes. [diseaseinfosearch.org]

  COMMON Features of the Disorder Failure to thrive Vomiting Low blood sugar levels Lethargy Small head size Seizures Developmental delay Weak muscle tone Muscle wasting PROGNOSIS Some individuals with the disorder may not develop any symptoms or crises [evolvegene.com]

  Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size (microcephaly).The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. [icdlist.com]

  Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size ( microcephaly ). The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. [ghr.nlm.nih.gov]

  Some show poor muscle tone, seizures, and small head size. If the disease is untreated, the child may show developmental delays and permanent learning difficulties. Some people with SCAD deficiency do not display any symptoms until adulthood. [counsyl.com]

• Muscle Hypotonia

  Genetic defect of SCAD was documented to cause clinical symptoms such as progressive psychomotor retardation, muscle hypotonia, and myopathy in early reports. [ncbi.nlm.nih.gov]

  Of those reported cases, hypoglycemia, developmental delay, and muscle hypotonia are the most common indicated features. [mayomedicallaboratories.com]

  As this publication included another SCADD patient who died after initial presentation with severe skeletal muscle hypotonia, a devastating clinical course of SCADD was suggested. [link.springer.com]

• Suggestibility

  Our results suggest that confirmatory tests may be useful to differentiate patients with common variants from those with deleterious mutations. [ncbi.nlm.nih.gov]

• Lethargy

  As a result, these fats are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy, hypoglycemia, and muscle weakness. [ghr.nlm.nih.gov]

  […] this condition typically includes a low-fat diet and avoidance of long periods without food (fasting). [2] Last updated: 2/5/2016 Some infants and children with SCAD deficiency may exhibit vomiting, low blood sugar ( hypoglycemia ), a lack of energy (lethargy [rarediseases.info.nih.gov]

  A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures [ncbi.nlm.nih.gov]

• Asthenia

  […] genotype Rhabdomyolysis (86%) Triggers: Activities requiring & promoting fatty acid oxidation Prolonged exercise Cold exposure Diet: Low-carbohydrate, High-fat diet; Fasting Infections & Fever Valproate treatment 7 Anaesthesia Other symptoms: Malaise; Asthenia [neuromuscular.wustl.edu]

Due to the rare occurrence of short chain acyl CoA dehydrogenase deficiency (approximately 1 in > 50,000 newborns according to isolated studies) [7], the diagnosis of this genetic condition may be difficult to make, especially in mildly symptomatic or asymptomatic patients. For this reason, a detailed examination comprised of a thorough clinical assessment and biochemical/genetic studies should be conducted. Firstly, patients (or the parents) should be asked about the course and progression of symptoms, and if a similar illness was observed in close family members, having in mind the autosomal recessive pattern of inheritance. In fact, Ashkenazi Jew ancestry is described as a potential risk factor for this condition, suggesting that ethnicity is also important [1]. After a comprehensive physical examination, blood and urine testing for toxic metabolites of fatty acid oxidation are the key steps in making the initial diagnosis [1] [6]. Increased urinary levels of ethylmalonic acid and butyryl-glycine and elevated butyryl-carnitine in plasma are main laboratory criteria for short chain acyl CoA dehydrogenase deficiency [1] [6]. These abnormalities can now be readily identified by tandem mass spectrometry during newborn screening [1], but only if a clear indication for their testing exists. A definite diagnosis is made by conducting genetic workup and confirmation of specific mutations on genes carrying SCAD information [1].

Management and treatment Most patients are asymptomatic and no treatment is needed. Some symptomatic patients are given riboflavin and follow a low fat/high carbohydrate diet and avoid fasting. [orpha.net]

Riboflavin treatment resulted in a decrease in EMA excretion in the mut/var group and in a subjective clinical improvement in four patients from this group. However, this improvement persisted after stopping treatment. [ncbi.nlm.nih.gov]

You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]

TREATMENT Treatment for SCAD Deficiency is symptomatic depending on the features of an individual. Treatment includes adequate nutrition/hydration, avoidance of periods of more than 12 hours without food, and carnitine supplements. [evolvegene.com]

Prognosis The prognosis is good in asymptomatic patients but variable in those who display the disease manifestations. The documents contained in this web site are presented for information purposes only. [orpha.net]

What is the prognosis for a person with Short Chain Acyl-CoA Dehydrogenase Deficiency? The prognosis for a person with SCAD deficiency varies widely and depends upon the severity of his or her symptoms. [counsyl.com]

\r\n \r\n The prognosis is good in asymptomatic patients, but those who have variable manifestations of the disease. \r\n [tellmegen.cl]

The prognosis of an affected individual depends on the severity of the symptoms. Management is typically overseen by a group of metabolic specialists. [nxgenmdx.com]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Etiology Symptomatic SCAD deficiency is due to mutations in the acyl-CoA dehydrogenase, C-2 to C-3 short chain ACADS gene (12q24.31) as well as additional as yet unidentified precipitating factors. [orpha.net]

Summary Epidemiology Approximately 50 patients have been identified worldwide to date. The Netherlands has an estimated birth prevalence of at least 1/50,000. [orpha.net]

In terms of treatment for short-chain acyl-CoA dehydrogenase deficiency, some individuals may not need treatment, while others might follow administration of: Riboflavin Dextrose Anticonvulsants This disorder, epidemiologically speaking, is thought to [en.wikipedia.org]

Cerevisiae, homolog of (FLAD1; FADS) ; Chromosome 1q21.3; Recessive Epidemiology: 9 patients Genetics Mutations: Biallelic, Frameshift, Missense or 1 amino acid deletion Mutation locations Molybdopterin binding (MPTb) domain, upstream of FADS domain: [neuromuscular.wustl.edu]

Genatlas disease for ACADS Gene myopathy,lipid storage Relevant External Links for ACADS Genetic Association Database (GAD) ACADS Human Genome Epidemiology (HuGE) Navigator ACADS Atlas of Genetics and Cytogenetics in Oncology and Haematology: ACADS The [genecards.org]

Moreover, our results provide insight into possible molecular pathophysiology of SCADD. [ncbi.nlm.nih.gov]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Short-chain acyl-CoA dehydrogenase (SCAD) catalyzes the first step in the mitochondrial beta-oxidation of fatty acids with a [mayomedicallaboratories.com]

The pathophysiology of MCAD deficiency results from the inability to carry out the first step of beta-oxidation. [emedicine.medscape.com]

Disease Explained: SCADD is an inherited metabolic disorder that prevents the body from converting certain types of fats into energy. [nxgenmdx.com]

Many of these complications can be prevented with early detection and lifelong management with a special diet and appropriate supplements. [diseaseinfosearch.org]

Reduced levels of this enzyme prevent short-chain fatty acids from being further broken down and processed in the mitochondria (the energy-producing centers inside cells ). [rarediseases.info.nih.gov]

Medicines, blood transfusions, and other procedures may help with complications. [ Read More ] Short-chain acyl-CoA dehydrogenase deficiency Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain [icdlist.com]

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting). [ghr.nlm.nih.gov]

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2. Corydon MJ, Vockley J, Rinaldo P, et al. Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr Res. 2001;49:18–23.
3. Amendt BA, Greene C, Sweetman L, et al. Short-chain acyl-coenzyme A dehydrogenase deficiency; clinical and biochemical studies in two patients. J Clin Invest. 1987;79:1303–1309.
4. Coates PM, Hale DE, Finocchiaro G, Tanaka K, Winter SC. Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. Journal of Clinical Investigation. 1988;81(1):171-175.
5. Turpin B, Tobias JD. Perioperative management of a child with short-chain acyl-CoA dehydrogenase deficiency. Paediatr Anaesth. 2005;15(9):771-777.
6. Waisbren SE, Levy HL, Noble M, et al. Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: An examination of the medical and neurodevelopmental characteristics of 14 cases identified through newborn screening or clinical symptoms. Mol Genet Metab. 2008;95(0):39-45.
7. van Maldegem BT, Duran M, Wanders RJA, et al. Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. JAMA. 2006;296:943–952