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Lipid proteinosis

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Hyalinosis cutis et mucosae; LIPOID PROTEINOSIS; Lipoid Proteinosis of Urbach and Wiethe; Lipoproteinosis; Urbach Wiethe disease
SNOMED CT: Lipid proteinosis (38692000); Hyalinosis cutis et mucosae (38692000); Lipoid proteinosis (38692000); Lipoidosis cutis et mucosae (38692000); Urbach-Wiethe disease (38692000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: 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).
Gene (location): ECM1 (1q21.2)
Monarch Initiative: MONDO:0009530
OMIM®: 247100
Orphanet: ORPHA530

Disease characteristics

Excerpted from the GeneReview: Lipoid Proteinosis
Lipoid proteinosis (LP) is characterized by deposition of hyaline-like material in various tissues resulting in a hoarse voice from early infancy, vesicles and hemorrhagic crusts in the mouth and on the face and extremities, verrucous and keratotic cutaneous lesions on extensor surfaces (especially the elbows), and moniliform blepharosis (multiple beaded papules along the eyelid margins and inner canthus). Extracutaneous manifestations may include epilepsy, neuropsychiatric disorders, spontaneous CNS hemorrhage, and asymptomatic multiple yellowish nodules throughout the gastrointestinal tract. Generally, the disease course is chronic and fluctuating. Males and females are affected equally. Affected individuals have a normal life span unless they experience laryngeal obstruction. [from GeneReviews]
Hassan Vahidnezhad  |  Leila Youssefian  |  Jouni Uitto   view full author information

Additional descriptions

Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane (summary by Hamada et al., 2002 and Hamada et al., 2003).  http://www.omim.org/entry/247100
From MedlinePlus Genetics
Lipoid proteinosis is a condition that results from the formation of numerous small clumps (deposits) of proteins and other molecules in various tissues throughout the body. These tiny clumps appear in the skin, upper respiratory tract, the moist tissues that line body openings such as the eyelids and the inside of the mouth (mucous membranes), and other areas.

The first symptom of this condition is usually a hoarse voice, which is due to deposits in the vocal cords. In infancy the hoarseness is expressed as a weak cry. The voice abnormalities persist throughout life and can ultimately cause difficulty speaking or complete loss of speech. Involvement of the throat, tonsils, and lips can result in breathing problems and upper respiratory tract infections. Deposits in the tongue can result in a thick and shortened tongue. They can also thicken the band of tissue that connects the tongue to the bottom of the mouth (frenulum), making it difficult to extend the tongue. The tongue may also have a smooth appearance due to damage to the taste buds.

A characteristic feature of lipoid proteinosis is the presence of multiple tiny, bead-like bumps lining the upper and lower eyelids along the lash line. These bumps are known as moniliform blepharosis. They may cause eyeball irritation or itching but generally do not impair vision.

The skin and mucous membranes are often fragile in children with lipoid proteinosis, leading to bleeding and scabbing following minor trauma. These problems often first appear in infancy in the mouth and on the face and limbs. Over time, these scabs form blisters and scars. Deposits accumulate in the skin, which causes the skin to become thickened and yellowish in color. Skin damage appears more frequently on areas that experience friction, such as the hands, elbows, knees, buttocks, and armpits. Some people with this condition have hair loss (alopecia) affecting their scalp, eyelashes, and eyebrows.

Neurologic features are also common in people with lipoid proteinosis. Affected individuals may have recurrent seizures (epilepsy) or behavioral and neurological problems, which can include headaches, aggressive behaviors, paranoia, hallucinations, short-term memory loss, and absence of fear. These features are thought to be associated with the presence of deposits and an accumulation of calcium (calcification) in areas of the brain called the temporal lobes. The temporal lobes help process hearing, speech, memory, and emotion. The brain abnormalities and neurological features do not always occur together, so the cause of the neurological features is still unclear.

Deposits can be found in some internal organs, including the stomach, a section of the small intestine called the duodenum, and the colon. The deposits in these tissues often do not cause any symptoms and may disappear over time.  https://medlineplus.gov/genetics/condition/lipoid-proteinosis

Clinical features

From HPO
Aggressive behavior
MedGen UID:
Concept ID:
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.
MedGen UID:
Concept ID:
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Memory impairment
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
An inappropriate feeling of being persecuted or being the subject of hostility from others.
Generalized non-motor (absence) seizure
MedGen UID:
Concept ID:
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
MedGen UID:
Concept ID:
Pathologic Function
A scar refers to a lesion in which wound, burn, or sore has not healed completely and fibrous connective tissue has developed.
Bilateral intracerebral calcifications
MedGen UID:
Concept ID:
Deposition of calcium salts on both sides of the cerebrum.
Temporal lobe calcification
MedGen UID:
Concept ID:
The presence of calcium deposition within the temporal lobe of the brain.
Hoarse voice
MedGen UID:
Concept ID:
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Skin plaque
MedGen UID:
Concept ID:
A plaque is a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter.
Thickened skin
MedGen UID:
Concept ID:
Laminar thickening of skin.
MedGen UID:
Concept ID:
A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point.
MedGen UID:
Concept ID:
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Patchy alopecia
MedGen UID:
Concept ID:
Transient, non-scarring hair loss and preservation of the hair follicle located in in well-defined patches.
Abnormal blistering of the skin
MedGen UID:
Concept ID:
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.
Skin erosion
MedGen UID:
Concept ID:
Disease or Syndrome
A discontinuity of the skin exhibiting incomplete loss of the epidermis, a lesion that is moist, circumscribed, and usually depressed.
Reduced epidermal extracellular matrix protein 1 protein expression
MedGen UID:
Concept ID:
Lower than normal amount of extracellular matrix protein 1 (ECM1) in the epidermis.
Papillary dermis eosinophilic hyaline material
MedGen UID:
Concept ID:
Accumulation of eosinophilic hyaline material observed around the papillary dermis and the blood vessels located in it. The papillary dermis is the uppermost layer of the dermis. It intertwines with the rete ridges of the epidermis and is composed of fine and loosely arranged collagen fibers.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLipid proteinosis
Follow this link to review classifications for Lipid proteinosis in Orphanet.

Professional guidelines


Dertlioğlu SB, Çalık M, Çiçek D
Int J Dermatol 2014 Apr;53(4):516-23. Epub 2013 Dec 10 doi: 10.1111/ijd.12254. PMID: 24320796
Huizar I, Kavuru MS
Curr Opin Pulm Med 2009 Sep;15(5):491-8. doi: 10.1097/MCP.0b013e32832ea51c. PMID: 19561506
Ann Intern Med 1954 Jul;41(1):163-71. doi: 10.7326/0003-4819-41-1-163. PMID: 13171802

Recent clinical studies


Findlay GH, Scott FP, Cripps DJ
Br J Dermatol 1966 Feb;78(2):69-80. doi: 10.1111/j.1365-2133.1966.tb12177.x. PMID: 5907437

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