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Disease Profile

Lathosterolosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Sterol c5-desaturase deficiency; SC5D deficiency

Categories

Congenital and Genetic Diseases; Metabolic disorders

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 46059

Definition
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
Only 4 cases have been reported in the literature to date.

Clinical description
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.

Etiology
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.

Diagnostic methods
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 diagnosis
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.

Antenatal diagnosis
Prenatal diagnosis is feasible if the mutations are known but it has never been performed given the rarity of the disease.

Genetic counseling
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.

Management and treatment
Treatment involves cholesterol supplementation and reduction of 7-hydrocholesterol. Simvastin, a 3-hydroxy-3-methylglutaryl coenzyme 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
The prognosis is poor but treatment appears to prolong life and arrest progression of neurological damage.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cataract
Cloudy lens
Clouding of the lens of the eye

[ more ]

0000518
Global developmental delay
0001263
Hypoplasia of penis
Underdeveloped penis
0008736
Microcephaly
Abnormally small skull
Small head circumference
Reduced head circumference
Decreased size of skull
Decreased circumference of cranium

[ more ]

0000252
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Specific learning disability
0001328
30%-79% of people have these symptoms
Abnormal platelet morphology
Abnormal shape of platelets
0011875
Abnormal thoracic spine morphology
0100711
Anisopoikilocytosis
0004823
Anteverted nares
Upturned nostrils
Upturned nose
Upturned nasal tip
Nasal tip, upturned

[ more ]

0000463
Arnold-Chiari malformation
0002308
Biparietal narrowing
0004422
Bulbous nose
0000414
Cerebellar cortical atrophy
0008278
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Epicanthus
Prominent eye folds
Eye folds

[ more ]

0000286
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Gingival overgrowth
Gum enlargement
0000212
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
High palate
Increased palatal height
Elevated palate

[ more ]

0000218
Horseshoe kidney
Horseshoe kidneys
0000085
Intrahepatic cholestasis
0001406
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Long philtrum
0000343
Meningocele
0002435
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Micrognathia
Little lower jaw
Small lower jaw
Small jaw

[ more ]

0000347
Muscular hypotonia
Low or weak muscle tone
0001252
Myoclonus
0001336
Narrow forehead
Decreased width of the forehead
0000341
Opacification of the corneal stroma
0007759
Postaxial hand polydactyly
Extra little finger
Extra pinky finger
Extra pinkie finger

[ more ]

0001162
Prominent metopic ridge
0005487
Ptosis
Drooping upper eyelid
0000508
Seizure
0001250
Short nose
Shortened nose
Decreased length of nose

[ more ]

0003196
Sloping forehead
Receding forehead
Inclined forehead

[ more ]

0000340
Talipes
0001883
Thrombocytopenia
Low platelet count
0001873
Toe syndactyly
Webbed toes
Fused toes

[ more ]

0001770
1%-4% of people have these symptoms
Abnormal circulating cholesterol concentration
Abnormality of cholesterol metabolism
0003107
Acanthocytosis
0001927
Ambiguous genitalia, male
Ambiguous genitalia in males
0000033
Bilobate gallbladder
0005608
Butterfly vertebrae
0003316
Cerebral atrophy
Degeneration of cerebrum
0002059
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Elevated alkaline phosphatase
Greatly elevated alkaline phosphatase
High serum alkaline phosphatase
Increased alkaline phosphatase
Increased serum alkaline phosphatase

[ more ]

0003155
Elevated hepatic transaminase
High liver enzymes
0002910
Foam cells with lamellar inclusion bodies
0003609
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hyperbilirubinemia
High blood bilirubin levels
0002904

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Lathosterolosis. Click on the link to view a sample search on this topic.

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