Lathosterolosis
Definicija
Lathosteroloza je izuzetno retka urođena greška biosinteze sterola koju karakteriše dismorfizam lica, urođene anomalije (uključujući anomalije ekstremiteta i bubrega), zastoj u napredovanju, zastoj razvoja i bolest jetre.
Pretraga
Pun naziv
Lathosterolosis
Kratki naziv
-
Sinonimi
Sterol C5-desaturase deficiency
Orpha broj
46059
Kategorija
Podkategorija
Naziv na stranom jeziku
-
Prevalenca
NULL
Nasleđivanje
Autosomal recessive
Period početka bolesti
-
ICD 10
Q87.8
OMIM
607330
UMLS
C1846421
GARD
9711
MEDDRA
Tekstualni opis
Microcephaly is present at birth along with hypotonia, failure to thrive and facial dysmorphic features such as bitemporal narrowing, ptosis, puffy cheeks, and micrognathia. Limb anomalies that have been reported include postaxial polydactyly of upper or lower limbs (mainly feet), bilateral syndactyly between the 2nd and 3rd or 2nd and 4th toes and bilateral club feet. Developmental delay and learning disability starting in early childhood have been noted in all patients. Additional anomalies have also been reported such as corneal clouding, cataract, conductive hearing loss, gingival hypertrophy, ambiguous genitalia, horseshoe kidney (see this term) and neurological manifestations (i.e. myoclonus). Liver disease seen in patients ranges from hypertransaminasemia to progressive cholestasis and can lead to end stage hepatic disease, occurring in childhood.
Etiologija
Lathosterolosis is due to mutations in the SC5D gene (11q23.3). A mutation in this gene leads to a deficiency in 3-beta-hydroxysteroid-delta-5-desaturase, which is necessary in the conversion of lathosterol into 7-dehydrocholesterol. This prevents the synthesis of cholesterol, which among other functions acts as a structural lipid, a precursor for bile acids and steroid hormones, and is necessary for the maturation of hedgehog morphogens during embryonic development.
Prognoza
bolest_prognoza
Diferencijalna dijagnoza
The main differential diagnosis is Smith-Lemli-Opitz syndrome (see this term) that shares many clinical features with lathosterolosis but that can be excluded with biochemical and genetic testing.
Tretman
Treatment involves cholesterol supplementation and reduction of 7-hydrocholesterol. Simvastin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, has been proven to be beneficial in normalizing the lathosterol level in one patient. Liver transplantation was successful in normalizing liver function and cholesterol levels in a patient who had developed end stage liver disease. Moreover, it appeared to improve neurocognitive functions. Regular opthalmological evalutations and ultrasound monitoring of the liver are recommended.
Dijagnostičke metode
Diagnosis is based on clinical and biochemical findings. An elevation of lathosterol by gas chromatography/mass spectroscopy (GC/MS) is noted in both skin fibroblasts and plasma. The levels of 7-dehydrocholesterol and cholesterol are normal or low. Molecular genetic testing revealing mutations in the SC5D gene confirms the diagnosis.
Antenatalna dijagnoza
Prenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease.
Epidemiologija
Only 4 cases have been reported in the literature to date.
Genetsko savetovanje
Lathosterolosis is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and they therefore have a 25% chance of having an affected child with each pregnancy.
Terapija
-
Klinička istraživanja
-