Short-chain acyl-CoA dehydrogenase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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).

Signs and symptoms of SCAD deficiency may appear during infancy or early childhood and can include vomiting, low blood glucose (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). 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. This disorder is sometimes mistaken for Reye syndrome, a severe condition that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

In some people with SCAD deficiency, signs and symptoms do not appear until adulthood. These individuals are more likely to have problems related to muscle weakness and wasting.

The severity of this condition varies widely, even among members of the same family. Some individuals are diagnosed with SCAD deficiency based on laboratory testing but never develop any symptoms of the condition.

ORPHANET DEFINITION Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a very rare inborn error of mitochondrial fatty acid oxidation characterized by variable manifestations ranging from asymptomatic individuals (in most cases) to those with failure to thrive, hypotonia, seizures, developmental delay and progressive myopathy.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: Unknown; Worldwide; Class only. Prevalence at birth: 1-9 / 100 000; Netherlands; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Elevated plasma acylcarnitine levels · Frequent (79-30%)

The concentration of fatty acylcarnitine in the blood circulation is above the upper limit of normal.

Ethylmalonic aciduria · Frequent (79-30%)

The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Feeding difficulties · Frequent (79-30%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Floppy infant · Frequent (79-30%)

Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).

Increased level of methylsuccinic acid in urine · Frequent (79-30%)

The concentration of methylsuccinic acid in the urine, normalized for urine concentration, is above the upper limit of normal.

Metabolic acidosis · Frequent (79-30%)

Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.

Neurodevelopmental delay · Frequent (79-30%)

Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.

Abnormal facial shape · Occasional (29-5%)

An abnormal morphology (form) of the face or its components.

Atypical behavior · Occasional (29-5%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Cardiomyopathy · Occasional (29-5%)

A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.

Delayed speech and language development · Occasional (29-5%)

A degree of language development that is significantly below the norm for a child of a specified age.

Dystonia · Occasional (29-5%)

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

Hepatic steatosis · Occasional (29-5%)

Steatosis is a term used to denote lipid accumulation within hepatocytes.

Other findings in the same source

From: Orphanet

Additional reported features include Hypoglycemic encephalopathy (Occasional (29-5%)); Ketotic hypoglycemia (Occasional (29-5%)); Lethargy (Occasional (29-5%)); Myopathy (Occasional (29-5%)); Respiratory distress (Occasional (29-5%)); Seizure (Occasional (29-5%)); Hypertonia (Very rare (<4-1%)); Intrauterine growth retardation (Very rare (<4-1%)); Microcephaly (Very rare (<4-1%)); Optic atrophy (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Childhood; Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: Unknown; Worldwide; Class only. Prevalence at birth: 1-9 / 100 000; Netherlands; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Short-chain acyl-CoA dehydrogenase deficiency is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Short-chain acyl-CoA dehydrogenase deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.