Lipoid proteinosis (Urbach–Wiethe disease)

Synonyms
Urbach-Wiethe-Syndrom, Hyalinosis cutis et mucosae, Lipoid proteinosis, Urbach-Wiethe disease
Specialty
Dermatology · Hereditary skin diseases
Images
Clinical 1 · Histology 1
In the app
2 flashcards
Last updated
10/2026 · Dr. Pascal Bafteh
Contents
  1. Images (2)
  2. Definition
  3. Occurrence & epidemiology
  4. Aetiopathogenesis
  5. Clinical features
  6. Histology
  7. Diagnosis
  8. Differential diagnoses
  9. Keep learning in the app
  10. References (selection)
  11. Cross-references

Images (2)

Lipoid proteinosis (Urbach–Wiethe disease) – AI illustration (not a patient photo): waxy papules, hoarse voice from birthAI illustration
waxy papules, hoarse voice from birth.AI-generated illustration for teaching purposes – not a real patient photo.
Lipoid proteinosis (Urbach–Wiethe disease) – histology (H&E): homogeneous, glassy eosinophilic hyaline deposits in a paucicellular dermal stroma with shrinkage clefts; onion-skin perivascular cuffing cannot be clearly identified, …Histology
histology (H&E): homogeneous, glassy eosinophilic hyaline deposits in a paucicellular dermal stroma with shrinkage clefts; onion-skin perivascular cuffing cannot be clearly identified, …TexasPathologistMSW, „3767 dp sl 2", CC BY-SA 4.0, via Wikimedia Commons · CC BY-SA 4.0 · Source
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Definition

Lipoid proteinosis (Urbach–Wiethe disease, hyalinosis cutis et mucosae) is a very rare, autosomal recessive genodermatosis with progressive deposition of amorphous hyaline material in the skin, mucous membranes and internal organs. A typical early symptom is hoarseness starting in early childhood.

Occurrence & epidemiology

Just over 500 cases have been reported worldwide, with men and women equally affected; there is often a positive family history or parental consanguinity. The disease is more frequent in Namaqualand (South Africa) owing to a founder effect.

Aetiopathogenesis

It is caused by loss-of-function mutations in the gene for extracellular matrix protein 1 (ECM1, chromosome 1q21). ECM1 binds numerous matrix proteins; its loss disturbs the structure of skin and mucosa, with reduplicated basement membrane around vessels and at the dermal–epidermal junction.

Clinical features

  • Hoarseness and a weak cry from infancy due to hyaline deposition in the laryngeal mucosa.
  • Skin: first recurrent blisters on the face and limbs with pock-like scars; later yellowish, waxy papules and diffuse skin thickening, verrucous lesions on elbows, knees and knuckles.
  • Moniliform blepharosis: bead-like yellowish papules along the eyelid margins, in about 50%.
  • Mouth: thickened frenulum with limited tongue mobility, thickened lips.
  • Central nervous system (50–75%): including epilepsy and behavioural changes, mainly due to calcification of the amygdala.

Histology

Homogeneous eosinophilic material in the dermis around vessels and adnexa; strongly PAS-positive, weakly positive or negative with Congo red.

Diagnosis

  • Suspected from typical features (hoarseness since infancy, moniliform blepharosis, thickened frenulum).
  • Biopsy: PAS-positive hyaline deposits.
  • CT/MRI: bilateral bean-shaped calcifications of the amygdala are considered pathognomonic.
  • Genetics: detection of biallelic ECM1 mutations confirms the diagnosis.

Differential diagnoses

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References (selection)

  1. DermNet: Lipoid proteinosis
  2. DermNet: Lipoid proteinosis pathology
  3. Lipoid proteinosis
  4. Lipoid proteinosis

Cross-references

Mentioned in

More hereditary skin diseases

Note: This page is intended for medical education and does not replace diagnosis or treatment decisions in individual cases.