Longitudinal Study of the Porphyrias

The porphyrias are a group of rare metabolic diseases that may present in childhood or adult
life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common
manifestations are related to accumulation of intermediates in the pathway and usually occur
as acute neurological attacks, or cutaneous photosensitivity. Multiple mutations have been
identified in each of the porphyrias. The risk of disability or death from these disorders is
significant, in part because diagnosis is often delayed due to lack of adoption of diagnostic
testing in clinical practice. Moreover, the natural history of these disorders is not well
described and it is not known what determines differences in outcomes. New therapies are
needed. For existing therapies, high-quality evidence on short and long term efficacy and
safety is generally lacking. Therefore, the purpose of this long-term follow-up study of a
large group of patients with the various porphyrias is to provide a better understanding of
the natural history of these disorders, as affected by available therapies, and to aid in
developing new forms of treatment.

The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a
Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes
and currently has funded 19 rare diseases clinical research consortia and one Data Management
and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study
the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions
listed in the participating institutions table. All Centers in the Porphyrias Consortium are
participating in the Longitudinal Study of the Porphyrias. Additional centers may be added if
funding is available.

The initial objective of this protocol is to assemble a well-documented group of patients
with confirmed diagnoses of specific porphyrias for clinical, biochemical, and genetic
studies. The long-term objective is to conduct a longitudinal investigation of the natural
history, complications, and therapeutic outcomes in people with acute and cutaneous
porphyria.

Inclusion Criteria:

- Individuals with a documented diagnosis of a porphyria.

- For each type of porphyria, the inclusion criteria are based on

- clinical features;

- biochemical findings, as documented by laboratory reports (or copies) of
porphyria-specific testing performed after 1980 (Absolute values are preferred
for diagnostic biochemical thresholds. Fold increases in comparison to an upper
(or lower) limit of normal (ULN or LLN) are also acceptable, but are complicated
by considerable variation between laboratories in normal limits. Equivocal
biochemical measurements may require confirmation by a consortium reference
laboratory;)

- molecular findings documenting the identification of a mutation in a
porphyria-related gene.

- In addition, an individual or a parent or guardian must be willing to give written
informed consent or assent, as appropriate.

- Provision is made for enrolling relatives who may not have symptoms but have
biochemical or molecular documentation of a porphyria, or in the case of recessive
disorders carry a disease-related mutation.

Exclusion Criteria:

- Cases with elevations of porphyrins in urine, plasma or erythrocytes due to other
diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone
marrow diseases;

- Patients with a prior diagnosis of porphyria that cannot be documented by review of
existing medical records or repeat biochemical or DNA testing.