VERY-LONG-CHAIN ACYL CoA DEHYDROGENASE DEFICIENCY (VLCAD)

Question 1

What is  VERY-LONG-CHAIN ACYL CoA DEHYDROGENASE DEFICIENCY (VLCAD)?

Accepted Answer

rare (1:85000)
autosomal recessive
3 phenotypes:
- severe form (early death, hypertrophic cardiomyopathy, early onset)
- milder form with late onset (hypoketotic hypoglycemia, no cardiac involvement)
- later occurrences in adolescents and adults (rhabdomyolysis, myoglobinuria )
Newborn screening for VLCADD suffers from a high false positive rate due to
false positive results in many heterozygotes and to elevated acylcarnitines
including C14:1 in some catabolic neonates even in the absence of ACADVL mutations [Simon EO2017]

Question 2

Gibt es eine deutsche Bezeichnung?

Accepted Answer

VLCADD [Very long chain Acyl-CoA-dehydrogenase deficiency]; Mangel an sehr langkettiger Acyl-CoA-Dehydrogenase

Question 3

What is the link to OMIM ?

Accepted Answer

OMIN 201475

Question 4

Which enzymes are involved?

Accepted Answer

Very long-chain specific acyl-CoA dehydrogenase, mitochondrial, Long-chain specific acyl-CoA dehydrogenase, mitochondrial

Disease	VERY-LONG-CHAIN ACYL CoA DEHYDROGENASE DEFICIENCY (VLCAD)
Synonym	VLCAD DEFICIENCY; ACADVLD
OMIM	201475 OMIM = Online Mendelian Inheritance of Men
Orphanet	26793
Protein (UniProt)	Very long-chain specific acyl-CoA dehydrogenase, mitochondrial, Long-chain specific acyl-CoA dehydrogenase, mitochondrial
Gene locus	17p13.1
ICD	E71.3
Summary	rare (1:85000) autosomal recessive 3 phenotypes: - severe form (early death, hypertrophic cardiomyopathy, early onset) - milder form with late onset (hypoketotic hypoglycemia, no cardiac involvement) - later occurrences in adolescents and adults (rhabdomyolysis, myoglobinuria ) Newborn screening for VLCADD suffers from a high false positive rate due to false positive results in many heterozygotes and to elevated acylcarnitines including C14:1 in some catabolic neonates even in the absence of ACADVL mutations [Simon EO2017]
Laboratory findings	Adipic acid inc (urine) Long chain acyl carnitines inc (plasma) Sebacic acid normal/inc (urine) Suberic acid normal/inc (urine) Tetradecenoylcarnitine (C14:1) n/i (dried blood spot (DB) Creatine kinase inc (serum) D-Glucose normal/dec (blood) Dicarboxylic acids inc (urine) Hexadecenoylcarnitine (C16:1) inc (plasma) Ketone bodies (urine) normal/inc (urine) L-Carnitine n/d (plasma) L-Carnitine n/d (dried blood spot (DB) Linoleoylcarnitine (C18:2) inc (plasma) Myoglobin inc (urine) Oleoylcarnitine (C18:1) inc (blood) Palmitoylcarnitine (C16) inc (blood) pH dec (blood) Tetradecadienoylcarnitine (C14:2) inc (blood) Tetradecanoylcarnitine (C14)/Propionylcarnitine (C3) inc (blood) Tetradecenoic acid inc (plasma) Tetradecenoylcarnitine (C14:1) n/i (plasma) Tetradecenoylcarnitine (C14:1)/ Dodecenoylcarnitine (C12:1) (plasma) Very-long-chain acyl-CoA dehydrogenase dec (fibroblasts)
Symptoms	cardiomyopathy coma hypotonia lethargy, drowsiness, apathy liver involvement or dysfunction myoglobinuria myopathy rhabdomyolysis cardiac arrest cardiomegaly cardiomyopathy, hypertrophic cardiomyopathy, mixed type early death encephalopathy hepatomegaly (large liver) hypoglycemia ketosis, ketoacidosis metabolic acidosis muscle weakness onset, adulthood onset, childhood onset, infancy onset, neonatal pain, muscle pericardial effusion respiratory insufficiency steatorrhea