Uncertain Diagnosis of Fabry Disease in Patients with Neuropathic Pain, Angiokeratoma or Cornea Verticillata: Consensus on the Approach to Diagnosis and Follow-Up.

[fabry disease]

Introduction : Individuals with neuropathic pain , angiokeratoma (AK ) and /or cornea verticillata (CV ) may be tested for Fabry disease (FD ). Classical FD is characterised by a specific pattern of these features . When a patient presents with a non-specific pattern , the pathogenicity of a variant in the α-galactosidase A (GLA ) gene may be unclear . This uncertainty often leads to considerable distress and inappropriate counselling and treatment . We developed a clinical approach for these individuals with an uncertain diagnosis of FD . Materials and Methods : A document was presented to an FD expert panel with background information based on clinical experience and the literature , followed by an online survey and a written recommendation . Results : The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain , AK and /or CV only , i .e . without kidney , heart or brain disease , with an uncertain diagnosis of FD . Only in the presence of FD -specific neuropathic pain (small fibre neuropathy with FD -specific pattern ), AK (FD -specific localisations ) or CV (without CV inducing medication ), FD is confirmed . When these features have a non-specific pattern , there is insufficient evidence for FD . If no alternative diagnosis is found , follow-up is recommended . Conclusions : In individuals with an uncertain diagnosis of FD , the presence of an FD -specific pattern of CV , AK or neuropathic pain is sufficient to confirm the diagnosis of FD . When these features are non-specific , a definite diagnosis can not (yet ) be established and follow-up is indicated . ERT should be considered only in those patients with a confirmed diagnosis of FD .

Diseases
Validation

Diseases presenting "pain" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

aniridia

aromatase deficiency

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cutaneous mastocytosis

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dracunculiasis

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

focal myositis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

junctional epidermolysis bullosa

kabuki syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

malignant atrophic papulosis

neuralgic amyotrophy

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

phenylketonuria

pleomorphic liposarcoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

scrub typhus

sneddon syndrome

systemic capillary leak syndrome

thoracic outlet syndrome

trochlear dysplasia

typhoid

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

wolf-hirschhorn syndrome

This symptom has already been validated