Lathosterolosis: Difference between revisions
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{{Infobox medical condition | |||
| name = Lathosterolosis | |||
| image = [[File:Lathosterol.png|left|thumb|Lathosterol]] | |||
| caption = Chemical structure of Lathosterol | |||
| synonyms = | |||
| pronounce = | |||
| specialty = [[Endocrinology]], [[Genetics]] | |||
| symptoms = Developmental delay, facial dysmorphism, liver disease | |||
| onset = | |||
| duration = | |||
| types = | |||
| causes = Mutations in the [[SC5D]] gene | |||
| risks = | |||
| diagnosis = [[Genetic testing]], [[Biochemical analysis]] | |||
| differential = [[Smith-Lemli-Opitz syndrome]], [[Cholesterol biosynthesis disorders]] | |||
| prevention = | |||
| treatment = [[Cholesterol supplementation]], [[Symptomatic treatment]] | |||
| medication = | |||
| prognosis = Variable, depending on severity | |||
| frequency = Extremely rare | |||
| deaths = | |||
}} | |||
=='''Alternate names'''== | =='''Alternate names'''== | ||
*Sterol c5-desaturase deficiency | *Sterol c5-desaturase deficiency | ||
*SC5D deficiency | *SC5D deficiency | ||
=='''Summary'''== | =='''Summary'''== | ||
Lathosterolosis is an extremely rare inborn error of [[sterol]] [[biosynthesis]] characterized by [[facial dysmorphism]], congenital anomalies (including limb and kidney anomalies), [[failure to thrive]], [[developmental delay]] and liver disease. | Lathosterolosis is an extremely rare inborn error of [[sterol]] [[biosynthesis]] characterized by [[facial dysmorphism]], congenital anomalies (including limb and kidney anomalies), [[failure to thrive]], [[developmental delay]] and liver disease. | ||
=='''Epidemiology'''== | =='''Epidemiology'''== | ||
Only 4 cases have been reported in the literature to date. | Only 4 cases have been reported in the literature to date. | ||
=='''Cause'''== | =='''Cause'''== | ||
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. | 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. | ||
=='''Inheritance'''== | |||
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. | 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. | ||
=='''Signs and symptoms'''== | =='''Signs and symptoms'''== | ||
* Microcephaly is present at birth along with [[hypotonia]], [[failure to thrive]] and facial dysmorphic features such as [[bitemporal narrowing]], [[ptosis]], puffy cheeks, and [[micrognathia]]. | * 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]]. | * 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]] and neurological manifestations (i.e. [[myoclonus]]). | * [[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]] 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. | * Liver disease seen in patients ranges from [[hypertransaminasemia]] to progressive [[cholestasis]] and can lead to end stage hepatic disease, occurring in childhood. | ||
=='''Diagnosis'''== | =='''Diagnosis'''== | ||
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]]. | 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. | The levels of [[7-dehydrocholesterol]] and [[cholesterol]] are normal or low. Molecular [[genetic testing]] revealing mutations in the SC5D gene confirms the diagnosis. | ||
'''Differential diagnosis'''The main differential diagnosis is [[Smith–Lemli–Opitz syndrome|Smith-Lemli-Opitz syndrome]] that shares many clinical features with lathosterolosis but that can be excluded with [[biochemical]] and [[genetic testing]]. | '''Differential diagnosis'''The main differential diagnosis is [[Smith–Lemli–Opitz syndrome|Smith-Lemli-Opitz syndrome]] that shares many clinical features with lathosterolosis but that can be excluded with [[biochemical]] and [[genetic testing]]. | ||
'''Antenatal diagnosis'''Prenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease. | '''Antenatal diagnosis'''Prenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease. | ||
=='''Treatment'''== | =='''Treatment'''== | ||
Treatment involves cholesterol supplementation and reduction of 7-hydrocholesterol. | 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. | [[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, Blood|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. | [[Liver transplantation]] was successful in normalizing liver function and [[Cholesterol, Blood|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. | ||
=='''Prognosis'''== | =='''Prognosis'''== | ||
The prognosis is poor but treatment appears to prolong life and arrest progression of neurological damage. | The prognosis is poor but treatment appears to prolong life and arrest progression of neurological damage. | ||
{{Defects of steroid metabolism}} | {{Defects of steroid metabolism}} | ||
[[Category:Cholesterol and steroid metabolism disorders]] | [[Category:Cholesterol and steroid metabolism disorders]] | ||
{{endocrine-disease-stub}} | {{endocrine-disease-stub}} | ||
{{rarediseases}} | {{rarediseases}} | ||
{{stub}} | {{stub}} | ||
Latest revision as of 00:29, 8 April 2025
Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD's medical weight loss NYC, sleep center NYC
Philadelphia medical weight loss and Philadelphia sleep clinics
| Lathosterolosis | |
|---|---|
| Synonyms | |
| Pronounce | |
| Specialty | Endocrinology, Genetics |
| Symptoms | Developmental delay, facial dysmorphism, liver disease |
| Complications | N/A |
| Onset | |
| Duration | |
| Types | |
| Causes | Mutations in the SC5D gene |
| Risks | |
| Diagnosis | Genetic testing, Biochemical analysis |
| Differential diagnosis | Smith-Lemli-Opitz syndrome, Cholesterol biosynthesis disorders |
| Prevention | |
| Treatment | Cholesterol supplementation, Symptomatic treatment |
| Medication | |
| Prognosis | Variable, depending on severity |
| Frequency | Extremely rare |
| Deaths | |
Alternate names[edit]
- Sterol c5-desaturase deficiency
- SC5D deficiency
Summary[edit]
Lathosterolosis is an extremely rare inborn error of sterol biosynthesis characterized by facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease.
Epidemiology[edit]
Only 4 cases have been reported in the literature to date.
Cause[edit]
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.
Inheritance[edit]
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.
Signs and symptoms[edit]
- 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 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.
Diagnosis[edit]
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. Differential diagnosisThe main differential diagnosis is Smith-Lemli-Opitz syndrome that shares many clinical features with lathosterolosis but that can be excluded with biochemical and genetic testing. Antenatal diagnosisPrenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease.
Treatment[edit]
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.
Prognosis[edit]
The prognosis is poor but treatment appears to prolong life and arrest progression of neurological damage.
| Inborn errors of steroid metabolism | ||||||||||||||||||||
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NIH genetic and rare disease info[edit]
Lathosterolosis is a rare disease.
| Rare and genetic diseases | ||||||
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Rare diseases - Lathosterolosis
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