Home > D. Systemic pathology > Genetic and developmental anomalies > Genetic metabolic diseases > lethal neonatal CPT deficiency type 2

lethal neonatal CPT deficiency type 2

MIM.608836

Thursday 17 March 2005

Autosomal recessive metabolic disease.

Synopsis

- craniofacial anomalies

  • Microcephaly
  • High, sloping forehead
  • Prominent forehead
  • Cararacts
  • Overfolded helices
  • Low-set ears
  • Posteriorly-rotated ears
  • Bulbous nose
  • High-arched palate
  • Narrow palate

- cardiovascular anomalies

  • Cardiomegaly
  • Dilated cardiomyopathy
  • Thickened myocardium
  • Arrhythmias
  • Sudden death within first days of life
  • Lipid accumulation in heart

- Respiratory distress
- Apnea
- Respiratory failure
- Widely spaced nipples

- heapatic anomalies

  • Hepatomegaly
  • Macrovesicular steatosis
  • Lipid accumulation in hepatocytes
  • Liver calcifications

- Gastrointestinal anomalies

  • Poor feeding

- urinary anomalies

  • Enlarged polycystic kidneys (detectable prenatally)
  • Dysplastic renal parenchyma
  • Hydronephrosis
  • Lipid accumulation in kidney, especially in proximal convoluted tubules
  • Renal insufficiency
  • Double ureters

- limb anomalies

  • Contractures of knees
  • Contractures of elbows
  • Long, tapering fingers
  • Extra digital creases in digits 2-4
  • Long, tapering toes
  • Hypoplastic toenails

- Lipid accumulation in skeletal muscle

- cerebrospinal anomalies

  • Neonatal hypotonia
  • Lethargy
  • Seizures
  • Ventriculomegaly
  • Intracerebral periventricular calcifications
  • Antenatal intracerebral hemorrhage
  • Dysplastic or absent corpus callosum
  • Polymicrogyria
  • Neuronal migration disorder
  • Paraventricular cysts
  • Basal ganglia cysts

- Oligohydramnios in some cases

Biology

- Nonketotic hypoglycemia
- Increased liver function tests
- Increased plasma long-chain acylcarnitines
- Increased tissue long-chain acylcarnitines
- Decreased plasma total and free carnitine
- Decreased tissue total and free carnitine
- Increased serum long-chain fatty acids
- Increased tissue long-chain fatty acids
- Long-chain dicarboxylic aciduria
- Hyperammonemia
- Increased total bilirubin
- Increased tissue levels of triglycerides
- Increased tissue levels of free fatty acids
- Severely decreased palmitate oxidation
- Severely decreased carnitine palmitoyltransferase II (CPT II) activity (less than 10% of normal) in multiple tissues
- Absence of CPT II protein

Etiology

- lethal neonatal form of carnitine palmitoyltransferase II (CPT2) deficiency is caused by mutation in the CPT2 gene )MIM.600650)

See also

- CPT deficiency type 2 infantile (MIM.600649)
- CPT deficiency type 2 late-onset (MIM.255110)