Transition to BioMetabol

Development of a new MS-based biomarker for the early and sensitive diagnosis of Hyaline fibromatosis syndrome from the blood

Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs. It represents a disease spectrum with infantile systemic hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF) being the mild form. Dermatologic manifestations include thickened skin, perianal nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on the scalp, hyperpigmented plaques over the metacarpophalangeal joints and malleoli, and joint contractures. ISH shows a severe visceral involvement, recurrent infections, and early death.

The lesions appear as pearly papules or fleshy nodules. The severity is variable. Some individuals present in infancy and have additional visceral or systemic involvement, which can lead to early death. These patients may show intractable diarrhea and increased susceptibility to infection. Other patients have later onset of a milder disorder affecting only the face and digits. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Histologic analysis of skin lesions shows proliferation of spindle-shaped cells forming strands in a homogeneous and hyaline eosinophilic extracellular material in the dermis.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Inclusion Criteria:

• Informed consent will be obtained from the parents before any study related procedures.
• Patients of both gender older than 2 months
• The patient has a diagnosis of Hyaline fibromatosis syndrome or a high-grade suspicion for Hyaline fibromatosis syndrome

High-grade suspicion present, if one or more inclusion criteria are valid:

• Positive family anamnesis for Hyaline fibromatosis syndrome
• Coarse facies
• Subcutaneous nodule
• Gingival fibromatosis
• Skeletal muscle atrophy
• Progressive flexion contractures

Exclusion Criteria:

• No Informed consent from the parents before any study related procedures.
• Patients of both gender younger than 2 months
• No diagnosis of Hyaline fibromatosis syndrome or no valid criteria for profound suspicion of Hyaline fibromatosis syndrome

Patients with Hyaline fibromatosis syndrome or high-grade suspicion for Hyaline fibromatosis syndrome