Preferred Label : Coq-responsive oxphos deficiency;
Type : Phenotype or locus, molecular basis unknown;
Description : Leshinsky-Silver et al. (2003) reported a 2-month-old male who was referred to clinic
for evaluation of cholestatic jaundice, pancreatic insufficiency, and hypertyrosinemia.
He was the first offspring of 2 healthy, highly consanguineous Azerbaijani Jews. Family
history was remarkable for 3 infant deaths: 2 severely retarded paternal aunts and
a maternal aunt who died of alleged sepsis. Pregnancy was normal until 35 weeks' gestation,
when it was terminated because of oligohydramion. Birth weight and head circumference
were age-appropriate and delivery was uneventful. On the fifth day of life the patient
became apathetic and mottled and refused eating. Metabolic evaluation revealed hyperammonemia,
which was treated with sodium benzoate and sodium phenylacetate, and severe respiratory
alkalosis with lacticacidosis. Tyrosine was 1,934 nmol/ml, alanine 607 nmol/ml, citrulline
76 nmol/ml, phenylalanine 424 nmol/ml, and lysine 426 nmol/ml. Urinary orotic acid
and succinylacetone were normal. On the sixth day of life spontaneous recovery occurred.
He developed mild hyperbilirubinemia and an elevated serum alpha-fetoprotein of 7,000
ng/ml (normal 0-15 ng/ml). On reevaluation at 2 months of age, he had cholestatic
jaundice and pancreatic insufficiency, with increased blood ammonia, increased lactic
acid, and elevated tyrosine. The serum alpha-fetoprotein was severely increased at
141,000 ng/ml. There was no indication of renal tubular acidosis, but urinary aminolevulinic
acid and porphobilinogen were high. Comprehensive evaluation was unrevealing, and
diagnostic liver biopsy showed prominent bridging, septal fibrosis, and widening of
portal spaces, with prominent mixed inflammatory infiltrate, associated with interface
hepatitis. Bile duct proliferation with numerous bile plugs was identified. The hepatic
lobules showed prominent cholestatic changes. Electron microscopy revealed hepatocytes
with a large number of mitochondria, which were altered in shape and size. Some mitochondria
were very large. Complex I III and complex II III were markedly reduced, while
complex II, IV, and citrate synthase (CS) were within the normal limits. The ratio
of I III/CS, I III/IV, II III/CS, and II III/IV were significantly reduced,
especially the last. The activity of complexes II III was restored by the addition
of CoQ1. Following the liver biopsy, CoQ treatment was instituted along with an antioxidant
cocktail and therapy for pancreatic insufficiency. Liver tests showed improvement,
but by the age of 9 months microcephaly, developmental delay, and sensorineural deafness
were evident. A brain MRI revealed bilateral hypodensities of the basal ganglia, characteristic
of Leigh disease (256000). Leshinsky-Silver et al. (2003) suggested that their patient
suffered from a CoQ biosynthesis defect, which would be consistent with the transient
tyrosinemia. The patient did not have neonatal liver insufficiency due to mitochondrial
depletion or deletion (e.g., 557000), as he had a completely normal complex IV activity.
Leshinsky-Silver et al. (2003) suggested that this case represented a neonatal autosomal
recessive disorder of CoQ biosynthesis with involvement of the gastrointestinal (liver
and pancreas) and central nervous systems. *FIELD* RF 1. Leshinsky-Silver, E.; Levine,
A.; Nissenkorn, A.; Barash, V.; Perach, M.; Buzhaker, E.; Shahmurov, M.; Polak-Charcon,
S.; Lev, D.; Lerman-Sagie, T.: Neonatal liver failure and Leigh syndrome possibly
due to CoQ-responsive;
Prefixed ID : %608158;
Origin ID : 608158;
UMLS CUI : C1842463;
Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
