Format

Send to:

Choose Destination

Lathosterolosis

MedGen UID:
375885
Concept ID:
C1846421
Disease or Syndrome
Synonyms: SC5D deficiency; Sterol c5-desaturase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Lathosterolosis (719257008); Sterol C5 desaturase deficiency (719257008)
 
Gene (location): SC5D (11q23.3-24.1)
OMIM®: 607330
Orphanet: ORPHA46059

Definition

An extremely rare inborn error of sterol biosynthesis with manifestations of facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease. Only 4 cases have been reported in the literature to date. 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. Inherited in an autosomal recessive manner. [from SNOMEDCT_US]

Clinical features

Talipes equinovarus
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Toe syndactyly
MedGen UID:
75581
Concept ID:
C0265660
Congenital Abnormality
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Postaxial foot polydactyly
MedGen UID:
384489
Concept ID:
C2112129
Finding
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Foam cells with lamellar inclusion bodies
MedGen UID:
871121
Concept ID:
C4025590
Finding
The presence of foam cells that contain lamellar inclusion bodies.
Growth delay
MedGen UID:
765377
Concept ID:
C3552463
Sign or Symptom
Intrahepatic cholestasis
MedGen UID:
3042
Concept ID:
C0008372
Disease or Syndrome
Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
An abnormal enlargement of both the liver and spleen.
Bilobate gallbladder
MedGen UID:
335420
Concept ID:
C1846422
Congenital Abnormality
The presence of a bilobed gallbladder, related to a duplication of the gallbladder primordium.
Elevated hepatic transaminases
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Arnold-Chiari malformation
MedGen UID:
2065
Concept ID:
C0003803
Congenital Abnormality
A group of congenital malformations involving the brainstem, cerebellum, upper spinal cord, and surrounding bony structures. Type II is the most common, and features compression of the medulla and cerebellar tonsils into the upper cervical spinal canal and an associated MENINGOMYELOCELE. Type I features similar, but less severe malformations and is without an associated meningomyelocele. Type III has the features of type II with an additional herniation of the entire cerebellum through the bony defect involving the foramen magnum, forming an ENCEPHALOCELE. Type IV is a form a cerebellar hypoplasia. Clinical manifestations of types I-III include TORTICOLLIS; opisthotonus; HEADACHE; VERTIGO; VOCAL CORD PARALYSIS; APNEA; NYSTAGMUS, CONGENITAL; swallowing difficulties; and ATAXIA. (From Menkes, Textbook of Child Neurology, 5th ed, p261; Davis, Textbook of Neuropathology, 2nd ed, pp236-46)
Myelocystocele
MedGen UID:
7538
Concept ID:
C0025312
Congenital Abnormality
A congenital abnormality in which the spinal cord and meninges protrude through a defect in the spinal column. The protrusion is above the skin surface.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Cerebral atrophy
MedGen UID:
892664
Concept ID:
C4020860
Disease or Syndrome
Schistocytosis
MedGen UID:
576247
Concept ID:
C0344386
Laboratory or Test Result
The presence of an abnormal number of fragmented red blood cells (schistocytes) in the blood.
Acanthocytosis
MedGen UID:
195801
Concept ID:
C0687751
Disease or Syndrome
Acanthocytosis is a type of poikilocytosis characterized by the presence of spikes on the cell surface. The cells have an irregular shape resembling many-pointed stars.
Increased mean platelet volume
MedGen UID:
853131
Concept ID:
C1096367
Finding
Average platelet volume above the upper limit of the normal reference interval.
Anisopoikilocytosis
MedGen UID:
436556
Concept ID:
C2675920
Finding
A test result indicating the presence of red cells of various sizes and shapes in the peripheral blood.
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A congenital abnormality in which the two kidneys fuse together during fetal development to create a horseshoe-shaped structure.
Ambiguous genitalia, male
MedGen UID:
867446
Concept ID:
C4021823
Finding
Ambiguous genitalia in an individual with XY genetic gender.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
An abnormal enlargement of both the liver and spleen.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
Abnormally high level of bilirubin in the blood. Excess bilirubin is associated with jaundice.
Elevated alkaline phosphatase
MedGen UID:
155461
Concept ID:
C0750857
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Abnormality of cholesterol metabolism
MedGen UID:
871179
Concept ID:
C4025656
Finding
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
Toe syndactyly
MedGen UID:
75581
Concept ID:
C0265660
Congenital Abnormality
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Butterfly vertebrae
MedGen UID:
337077
Concept ID:
C1844752
Congenital Abnormality
In the orthopedic and radiological literature, sagittally cleft vertebra is generally known as a butterfly vertebra.
Postaxial foot polydactyly
MedGen UID:
384489
Concept ID:
C2112129
Finding
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Lumbosacral meningocele
MedGen UID:
436462
Concept ID:
C2675557
Finding
Osteoporosis
MedGen UID:
776590
Concept ID:
C2911643
Finding
Gingival overgrowth
MedGen UID:
6603
Concept ID:
C0017567
Disease or Syndrome
Abnormal enlargement or overgrowth of the gingivae brought about by enlargement of existing cells.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Reduced width of the skin of vermilion border region of upper lip.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Thick upper lip vermilion
MedGen UID:
339521
Concept ID:
C1846423
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle.
Opacification of the corneal stroma
MedGen UID:
347281
Concept ID:
C1856661
Finding
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLathosterolosis
Follow this link to review classifications for Lathosterolosis in Orphanet.

Recent clinical studies

Etiology

Calvo PL, Brunati A, Spada M, Romagnoli R, Corso G, Parenti G, Rossi M, Baldi M, Carbonaro G, David E, Pucci A, Amoroso A, Salizzoni M
Am J Transplant 2014 Apr;14(4):960-5. Epub 2014 Mar 12 doi: 10.1111/ajt.12645. PMID: 24621408
Cavallini GM, Masini C, Chiesi C, Campi L, Rivasi F, Ferrari P
Eur J Ophthalmol 2009 Jan-Feb;19(1):139-42. PMID: 19123163
Rossi M, D'Armiento M, Parisi I, Ferrari P, Hall CM, Cervasio M, Rivasi F, Balli F, Vecchione R, Corso G, Andria G, Parenti G
Am J Med Genet A 2007 Oct 15;143A(20):2371-81. doi: 10.1002/ajmg.a.31929. PMID: 17853487
Krakowiak PA, Wassif CA, Kratz L, Cozma D, Kovárová M, Harris G, Grinberg A, Yang Y, Hunter AG, Tsokos M, Kelley RI, Porter FD
Hum Mol Genet 2003 Jul 1;12(13):1631-41. PMID: 12812989
Brunetti-Pierri N, Corso G, Rossi M, Ferrari P, Balli F, Rivasi F, Annunziata I, Ballabio A, Russo AD, Andria G, Parenti G
Am J Hum Genet 2002 Oct;71(4):952-8. Epub 2002 Aug 20 doi: 10.1086/342668. PMID: 12189593Free PMC Article

Diagnosis

Rossi M, Hall CM, Bouvier R, Collardeau-Frachon S, Le Breton F, Bucourt M, Cordier MP, Vianey-Saban C, Parenti G, Andria G, Le Merrer M, Edery P, Offiah AC
Pediatr Radiol 2015 Jul;45(7):965-76. Epub 2015 Feb 3 doi: 10.1007/s00247-014-3257-9. PMID: 25646736
Calvo PL, Brunati A, Spada M, Romagnoli R, Corso G, Parenti G, Rossi M, Baldi M, Carbonaro G, David E, Pucci A, Amoroso A, Salizzoni M
Am J Transplant 2014 Apr;14(4):960-5. Epub 2014 Mar 12 doi: 10.1111/ajt.12645. PMID: 24621408
Jira P
Handb Clin Neurol 2013;113:1845-50. doi: 10.1016/B978-0-444-59565-2.00054-X. PMID: 23622407
Rossi M, D'Armiento M, Parisi I, Ferrari P, Hall CM, Cervasio M, Rivasi F, Balli F, Vecchione R, Corso G, Andria G, Parenti G
Am J Med Genet A 2007 Oct 15;143A(20):2371-81. doi: 10.1002/ajmg.a.31929. PMID: 17853487
Rossi M, Vajro P, Iorio R, Battagliese A, Brunetti-Pierri N, Corso G, Di Rocco M, Ferrari P, Rivasi F, Vecchione R, Andria G, Parenti G
Am J Med Genet A 2005 Jan 15;132A(2):144-51. doi: 10.1002/ajmg.a.30426. PMID: 15580635

Prognosis

Calvo PL, Brunati A, Spada M, Romagnoli R, Corso G, Parenti G, Rossi M, Baldi M, Carbonaro G, David E, Pucci A, Amoroso A, Salizzoni M
Am J Transplant 2014 Apr;14(4):960-5. Epub 2014 Mar 12 doi: 10.1111/ajt.12645. PMID: 24621408
Kanungo S, Soares N, He M, Steiner RD
Dev Disabil Res Rev 2013;17(3):197-210. doi: 10.1002/ddrr.1114. PMID: 23798009
Rossi M, Vajro P, Iorio R, Battagliese A, Brunetti-Pierri N, Corso G, Di Rocco M, Ferrari P, Rivasi F, Vecchione R, Andria G, Parenti G
Am J Med Genet A 2005 Jan 15;132A(2):144-51. doi: 10.1002/ajmg.a.30426. PMID: 15580635

Clinical prediction guides

Rossi M, Hall CM, Bouvier R, Collardeau-Frachon S, Le Breton F, Bucourt M, Cordier MP, Vianey-Saban C, Parenti G, Andria G, Le Merrer M, Edery P, Offiah AC
Pediatr Radiol 2015 Jul;45(7):965-76. Epub 2015 Feb 3 doi: 10.1007/s00247-014-3257-9. PMID: 25646736
Calvo PL, Brunati A, Spada M, Romagnoli R, Corso G, Parenti G, Rossi M, Baldi M, Carbonaro G, David E, Pucci A, Amoroso A, Salizzoni M
Am J Transplant 2014 Apr;14(4):960-5. Epub 2014 Mar 12 doi: 10.1111/ajt.12645. PMID: 24621408

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center