Mitochondrial hepatopathy: Anticipated difficulties in management of fatty acid oxidation defects and urea cycle defects

Table 1 Characteristic findings in clinically significant Fatty acid oxidation defects

Deficiency	Presentation	General biochemical abnormalities	Fatty acid metabolites	Gene	Newborn screen	Treatment
OCTN2	Hepatomegaly; Lethargy; Encephalopathy; Hypotonia	Raised transaminases; Hyperammonemia; Lactic acidosis	Low plasma acyl carnitine and free carnitine, high urine carnitine	SLC22A5	Low free carnitine	Carnitine supplementation
CPT-1	Reye-like syndrome; Renal tubular acidosis	Raised transaminases; Acidosis; Hyperammonemia	High free carnitine, low long chain acyl carnitine	CPT-1A	Increased free carnitine	Avoid fasting; Uncooked cornstarch; Medium chain triglyceride supplements
CACT	Coma; Cardiomyopathy; Apnoea; Seizures	Raised transaminases; Hyperammonemia; Elevated creatine phosphokinase	Low free carnitine, high long chain acyl carnitine, high urine dicarboxylic acid	SLC25A20	Increased long chain acyl carnitine	High carbohydrate low long chain fat diet; Medium chain triglyceride supplements; Carnitine
CPT-2	Encephalopathy; Hypotonia; Myalgia; Myoglobinuria; Neuronal migration defects; Cardiomegaly; Nephromegaly	Raised transaminases; Hyperammonemia; Elevated creatine phosphokinase	Low free carnitine, high long chain acyl carnitine, high urine dicarboxylic acid	CPT-2	High long chain acyl carnitine (C16, C16:1, C18, C18:1)	Intravenous glucose; Night-time feeds; High carbohydrate low long chain fat diet; Medium chain triglyceride supplements; Carnitine; Bezafibrate
VLCAD	Hypertrophic cardiomyopathy; Encephalopathy; Exercise induced myolysis	Raised transaminases; Hyperammonemia; Elevated creatine phosphokinase; High lactate	Low free carnitine, High C12, C14:1, C16 acylcarnitines.	ACADVL	High C12, C14:1, C16 acylcarnitine	Night-time feeds; High carbohydrate low long chain fat diet; Medium chain triglyceride supplements; Bezafibrate; Triheptanoin
MCAD	Vomiting; Lethargy; Encephalopathy	Hypoketotic hypoglycemia; Raised transaminases, ammonia, lactate, creatine phosphokinase, uric acid, blood urea nitrogen	High medium chain acyl carnitine; Free carnitine may be low or normal. Urine: Dicarboxylic acid, suberyl glycine, hexanoyl glycine	ACADM	High C6:0-, C8:0-, C10:0- and C10:1-acylcarnitines	Frequent feeding; Uncooked cornstarch
SCAD1	Hypotonia; Seizures; Failure to thrive; Behavioral disorders	Raised transaminases, ammonia, lactate, uric acid, blood urea nitrogen, mild acidosis	High C4 carnitine, ethymalonic acid in urine	ACADS	High C4 carnitine	Frequent feeding; Riboflavin; Carnitine
LCHAD	Hypotonia; Hepatomegaly; Rhabdomyolysis; Retinitis pigmentosa; Peripheral neuropathy; HELLP syndrome in mothers	Raised transaminases, ammonia, lactate, creatine phosphokinase	Low free carnitine; High hydroxyacyl carnitine; Hydroxydicarboxylic acid in urine	HADHA	High long chain hydroxyacyl carnitine	Intravenous glucose; Night-time feeds; Uncooked cornstarch; Medium chain triglyceride supplement; Docosahexaenoic acid supplement; Triheptanoin

¹Clinical relevance is still ambiguous.

OCTN2: Organic cation transporter 2; CPT: Carnitine palmitoyltransferase; CACT: Carnitine acyl carnitine transporter; VLCAD: Very long chain acyl CoA dehydrogenase; MCAD: Medium chain acyl CoA dehydrogenase; SCAH: Short chain acyl CoA dehydrogenase; LCHAD: Long chain hydroxyl acyl CoA dehydrogenase.