# ERYTHROPOIETIC PROTOPORPHYRIA: MECHANISMS OF DISEASE

> **NIH NIH R01** · NEW YORK MEDICAL COLLEGE · 1993 · $263,745

## Abstract

DESCRIPTION (Adapted from the applicant's abstract):  Human protoporphyria
is a genetically determined metabolic defect in heme biosynthesis.  Partial
deficiency in the activity of the enzyme ferrochelatase (FC) in bone marrow
erythroid cells results in accumulation of protoporphyrin (PP) in rbc,
plasma, liver, and feces.  PP causes painful cutaneous photosensitivity and
may lead to fatal hepatotoxicity in affected children and adults.  Much
remains unknown about the natural course of human protoporphyria and about
its disease mechanisms in skin, bone marrow, and liver.  Continuation of
ongoing longitudinal investigations of an established protoporphyria study
population with a standardized protocol that has already built a data base
for 8 years or longer in the majority of 24 currently participating
patients, will further advance current understanding of how this disease
evolves in a large number of carefully studied individual patients over
many years of time.  Individual patients may benefit from early detection
of adverse changes in hepatic function.  Factors leading to development of
fatal hepatotoxicity may be learned from retrospective analysis of the
accumulated data base for patients who develop liver dysfunction when
compared with the data of the population as a whole.  Elucidation of the
structure and function of human FC will be advanced by biochemical and
immunological methods.  Purified FC protein produced by novel
chromatographic methods that the investigators have already developed will
be used to produce polyclonal and monoclonal antibodies useful for
characterization studies of mutant versus normal human FCs proposed herein.
Development of such immunological reagents and of oligonucleotide probes
constructed according to amino acid sequence information derived from
peptides cleaved from purified human FC will enable them, in future years,
to propose to clone and express the gene for human FC, to initiate a search
for its chromosomal assignment, and to determine the precise nature of the
FC mutation responsible for human protoporphyria.  In vivo stability of FC
in bone marrow will be evaluated first in drug-induced rat erythropoiesis
and myelopoiesis models, then in human protoporphyric bone marrow.
Clinical and laboratory evaluations of unusual cases of several related
forms of porphyria that have already provided new information regarding
this group of diseases will be continued.  In particular, immunomapping of
the microanatomical level of the epidermal-dermal separation in porphyria
cutanea tarda will be carried out to target appropriate biomolecular
components of the basement membrane zone for further study.

## Key facts

- **NIH application ID:** 3154991
- **Project number:** 5R01AR018549-18
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **SAM.gov UEI:** WK63UJ11C2H7
- **Principal Investigator:** MAUREEN B POH-FITZPATRICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $263,745
- **Award type:** 5
- **Project period:** 1987-02-01 → 1994-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154991

## Citation

> US National Institutes of Health, RePORTER application 3154991, ERYTHROPOIETIC PROTOPORPHYRIA: MECHANISMS OF DISEASE (5R01AR018549-18). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154991. Licensed CC0.

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