Table 3. [Genetic Disorders of Interest in the Differential Diagnosis of LCHAD/TFP Deficiency]. - GeneReviews®

Gene(s)	Disorder ¹	Key Features Overlapping w/LCHAD/TFP Deficiency	Distinguishing Features ²
ACADM	Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency	Intermittent hypoketotic hypoglycemia precipitated by fasting or illness; Reye syndrome-like presentation	Absence of myopathy, cardiomyopathy, peripheral neuropathy, & retinopathy in MCAD deficiency
ACADVL	Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency	Severe early-onset form: cardiomyopathy & multiorgan failure Intermediate form: intermittent hypoketotic hypoglycemia Late-onset myopathic form: recurrent rhabdomyolysis	Absence of peripheral neuropathy & retinopathy in VLCAD deficiency
CPT1A	Carnitine palmitoyltransferase 1A (CPT1A) deficiency	Intermittent hypoketotic hypoglycemia & liver failure	Absence of peripheral neuropathy & retinopathy in CPT1A deficiency
CPT2	Carnitine palmitoyltransferase II (CPT II) deficiency	Lethal neonatal form: hypoglycemia, liver failure, cardiomyopathy Severe infantile hepatocardiomuscular form: intermittent hypoketotic hypoglycemia, liver failure, cardiomyopathy Late-onset myopathic form: recurrent rhabdomyolysis	Congenital anomalies (cystic/dysplastic kidneys, neuronal migration defects) may be present in lethal neonatal form of CPT II deficiency. CPT II deficiency is not assoc w/peripheral neuropathy or retinopathy.
ETFA ETFB ETFDH	Multiple acyl-CoA dehydrogenase deficiency (MADD)	Severe neonatal form: hypoglycemia, metabolic acidosis, lactic acidosis, hyperammonemia, hepatomegaly, cardiomyopathy Late-onset form: recurrent metabolic decompensation consisting of hypoglycemia & metabolic acidosis, recurrent rhabdomyolysis	Congenital anomalies may be present in severe neonatal form of MADD. Peripheral neuropathy has been described in MADD, but retinopathy has not been assoc w/MADD.
SLC22A5	Systemic primary carnitine deficiency (CDSP)	Intermittent hypoketotic hypoglycemia precipitated by fasting or illness, skeletal myopathy, cardiomyopathy	Absence of peripheral neuropathy & retinopathy in CDSP
SLC25A20	Carnitine-acylcarnitine translocase (CACT) deficiency	Severe neonatal form: hypoglycemia, hyperammonemia, liver failure, ↑ CK, cardiomyopathy Late-onset form (rare): recurrent metabolic decompensation consisting of hypoketotic hypoglycemia	Absence of peripheral neuropathy & retinopathy in CACT deficiency

Gene(s)

Disorder ¹

Key Features Overlapping w/LCHAD/TFP Deficiency

Distinguishing Features ²

ACADM

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Intermittent hypoketotic hypoglycemia precipitated by fasting or illness; Reye syndrome-like presentation

Absence of myopathy, cardiomyopathy, peripheral neuropathy, & retinopathy in MCAD deficiency

ACADVL

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

Severe early-onset form: cardiomyopathy & multiorgan failure
Intermediate form: intermittent hypoketotic hypoglycemia
Late-onset myopathic form: recurrent rhabdomyolysis

Absence of peripheral neuropathy & retinopathy in VLCAD deficiency

CPT1A

Carnitine palmitoyltransferase 1A (CPT1A) deficiency

Intermittent hypoketotic hypoglycemia & liver failure

Absence of peripheral neuropathy & retinopathy in CPT1A deficiency

CPT2

Carnitine palmitoyltransferase II (CPT II) deficiency

Lethal neonatal form: hypoglycemia, liver failure, cardiomyopathy
Severe infantile hepatocardiomuscular form: intermittent hypoketotic hypoglycemia, liver failure, cardiomyopathy
Late-onset myopathic form: recurrent rhabdomyolysis

Congenital anomalies (cystic/dysplastic kidneys, neuronal migration defects) may be present in lethal neonatal form of CPT II deficiency.
CPT II deficiency is not assoc w/peripheral neuropathy or retinopathy.

ETFA
ETFB
ETFDH

Multiple acyl-CoA dehydrogenase deficiency (MADD)

Severe neonatal form: hypoglycemia, metabolic acidosis, lactic acidosis, hyperammonemia, hepatomegaly, cardiomyopathy
Late-onset form: recurrent metabolic decompensation consisting of hypoglycemia & metabolic acidosis, recurrent rhabdomyolysis

Congenital anomalies may be present in severe neonatal form of MADD.
Peripheral neuropathy has been described in MADD, but retinopathy has not been assoc w/MADD.

SLC22A5

Systemic primary carnitine deficiency (CDSP)

Intermittent hypoketotic hypoglycemia precipitated by fasting or illness, skeletal myopathy, cardiomyopathy

Absence of peripheral neuropathy & retinopathy in CDSP

SLC25A20

Carnitine-acylcarnitine translocase (CACT) deficiency

Severe neonatal form: hypoglycemia, hyperammonemia, liver failure, ↑ CK, cardiomyopathy
Late-onset form (rare): recurrent metabolic decompensation consisting of hypoketotic hypoglycemia

Absence of peripheral neuropathy & retinopathy in CACT deficiency

From: Long-Chain Hydroxyacyl-CoA Dehydrogenase Deficiency / Trifunctional Protein Deficiency

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