Systemic primary carnitine deficiency (212140*)

Plasma membrane carnitine transport OCTN2

Biochemical profile: High urinary carnitine excretion despite very low plasma carnitine, absence of significant dicarboxylic aciduria

Clinical features: Hypoketotic hypoglycemia, fasting intolerance with hypotonia, depressed central nervous system, apnea, seizures, dilated cardiomyopathy, developmental delay

Treatment: L-Carnitine

Long-chain fatty acid transport deficiency (603376*)

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Biochemical profile: Low to normal free carnitine; during acute episodes, elevated plasma C8–C18 acylcarnitine esters

Clinical features: Episodic acute liver failure, hyperammonemia, encephalopathy

Treatment: Liver transplantation

Carnitine palmitoyltransferase I (CPT-I) deficiency (255120*)

CPT-I

Biochemical profile: Normal to elevated total and free plasma carnitine, no dicarboxylic aciduria

Clinical features: Fasting intolerance, hypoketotic hypoglycemia, hepatomegaly, seizures, coma, elevated creatine kinase

Treatment: Avoidance of fasting; frequent feeding; during acute episodes, high-dose glucose; replacement of long-chain dietary fat with medium-chain fat

Carnitine/acylcarnitine translocase deficiency (212138*)

Carnitine/acylcarnitine translocase

Biochemical profile: Low total plasma carnitine, with most conjugated to long-chain fatty acids; elevated C16 carnitine ester

Clinical features: In the neonatal form, fasting intolerance with hypoglycemic coma, vomiting, weakness, cardiomyopathy, arrhythmia, mild hyperammonemia

In the mild form, recurrent hypoglycemia with no cardiac involvement

Treatment: Avoidance of fasting; frequent feeding; if plasma level is low, carnitine; during acute episodes, high-dose glucose

Carnitine palmitoyltransferase II (CPT-II) deficiency (255110*, 600649* [infantile form], 608836* [lethal neonatal form])

CPT-II

Biochemical profile: Elevated C16 carnitine ester

In the classical muscle form, carnitine usually normal

In the severe form, low total plasma carnitine, with most conjugated to long-chain fatty acids

Clinical features: In the classical muscle form, presentation in adulthood with muscle pain and episodic myoglobinuria and weakness after prolonged exercise, fasting, intercurrent illness, or stress

In the severe form, presentation in neonatal period or infancy with hypoketotic hypoglycemia, cardiomyopathy, arrhythmia, hepatomegaly, coma, or seizures

Treatment: Avoidance of fasting; frequent feeding; if plasma level is low, carnitine; during acute episodes, high-dose glucose

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (201475*)

VLCAD

Biochemical profile: Elevated saturated and unsaturated C14–C18 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, hyperammonemia, elevated liver enzymes

Treatment: Avoidance of fasting; high-carbohydrate diet; carnitine; medium-chain triglycerides; during acute episodes, high-dose glucose

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (600890*)

LCHAD

Biochemical profile: Elevated saturated and unsaturated C16–C18 acylcarnitine esters, elevated urinary C6–C14 3-hydroxydicarboxylic acids

Clinical features: Fasting-induced hypoketotic hypoglycemia, exercise-induced rhabdomyolysis, cardiomyopathy, cholestatic liver disease, retinopathy, maternal HELLP syndrome

Treatment: Avoidance of fasting; high-carbohydrate diet; carnitine; medium-chain triglycerides; during acute episodes, high-dose glucose

For retinopathy, docosahexanoic acid possibly useful

Mitochondrial trifunctional protein (TFP) deficiency (609015*)

Mitochondrial TFP

Biochemical profile: Similar to LCHAD deficiency

Clinical features: Liver failure, cardiomyopathy, fasting hypoglycemia, myopathy, sudden death

Treatment: Similar to that for LCHAD deficiency

Alpha-subunit

Beta-subunit

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (201450*)

MCAD

Biochemical profile: Elevated saturated and unsaturated C8–C10 acylcarnitine esters; elevated urinary C6–C10 dicarboxylic acids, suberylglycine, and hexanoylglycine; low free carnitine

Clinical features: Episodic hypoketotic hypoglycemia after fasting, vomiting, hepatomegaly, lethargy, coma, acidosis, sudden infant death syndrome, Reye-like syndrome

Treatment: Avoidance of fasting; frequent feeding, including bedtime snacks; high-carbohydrate diet; carnitine; during acute episodes, high-dose glucose

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency (201470*)

SCAD

Biochemical profile: In the neonatal form, intermittent ethylmalonic aciduria

In the chronic form, low muscle carnitine

Clinical features: In the neonatal form, neonatal acidosis, vomiting, growth and developmental delay

In the chronic form, progressive myopathy

Treatment: Avoidance of fasting

Glutaric aciduria type II (231680*)

Electron transfer flavoprotein (ETF)

Biochemical profile: Elevated urinary ethylmalonic, glutaric, 2-hydroxyglutaric, 3-hydroxyisovaleric, and C6–C10 dicarboxylic acids and isovalerylglycine; elevated glutarylcarnitine, isovalerylcarnitine, and straight-chain acylcarnitine esters of C4, C8, C10, C10:1, and C12 fatty acids; low serum carnitine; increased serum sarcosine

Clinical features: Fasting hypoketotic hypoglycemia, acidosis, sudden death, central nervous system anomalies, myopathy, possibly liver and cardiac involvement

Treatment:

Alpha-subunit

Beta-subunit

ETF:ubiquinone oxidoreductase (ETF:QO)

Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency (601609*)

SCHAD

Biochemical profile: Ketotic C8–C14 3-hydroxydicarboxylic aciduria

Clinical features: Recurrent myoglobinuria, ketonuria, hypoglycemia, encephalopathy, cardiomyopathy

Treatment: Avoidance of fasting

Short/medium-chain 3-hydroxyacyl-CoA dehydrogenase (S/MCHAD) deficiency

S/MCHAD

Biochemical profile: Marked elevation of MCHADs and acylcarnitines

Clinical features: Liver failure, encephalopathy

Treatment: Avoidance of fasting

Medium-chain 3-ketoacyl-CoA thiolase (MCKAT) deficiency (602199*)

MCKAT

Biochemical profile: Lactic aciduria, ketosis, elevated urinary C4–C12 dicarboxylic aciduria (especially C10 and C12)

Clinical features: Fasting intolerance, vomiting, dehydration, metabolic acidosis, liver dysfunction, rhabdomyolysis

Treatment: Avoidance of fasting

2,4-Dienoyl-CoA reductase deficiency (222745*)

2,4-Dienoyl-CoA reductase

Biochemical profile: Hyperlysinemia, low plasma carnitine, 2-trans,4-cis decadienoylcarnitine in plasma and urine

Clinical features: Neonatal hypotonia, respiratory acidosis

Treatment: Not established