Background

Hereditary Coproporphyria is an infrequent inherited enzyme deficiency disorder i.e. (coproporphyrinogen oxidase), related to the step in producing heme. This deficiency results in the builds of certain porphyrin’s precursors, particularly coproporphyrinogen, throughout the body which may occur and develop a range of symptoms. 

A person with HCP may experience various symptoms ranging from abdominal pain, neurological disturbances, psychiatric symptoms, and skin manifestations (e.g. photosensitivity, blistering). Usually, these conditions manifest randomly and can be caused by such factors as specific medications, hormonal alterations and period of fasting or alcohol intake. 

Epidemiology

Scientists conducted a prospective study with a cross-sectional investigation of the clinical and biochemical cases of patients with inherited porphyria’s from 11 European nations. The results showed that the mean annual incidence ranged from zero to twenty cases per million people with symptomatic hereditary coproporphyria, confirmed through laboratory testing. 

Anatomy

Pathophysiology

Genetic Mutation: Mutation in the CPOX gene residing on chromosome 3p disables or impairs the CPOX enzyme activity responsible for the CPOX pathway, hence for HCP. 

Enzyme Deficiency: Deletion or substitution gives the altered form where normally the CPOX enzyme would generate protoporphyrinogen IX from coproporphyrinogen III in heme synthesis. 

 Porphyrin Precursor Accumulation: With minimum CPOX enzyme production, porphyrin tissues accumulate in the liver and other organs, including coproporphyrinogen III and coproporphyrin III, which can yield reactive oxygen species when exposed to light. 

 Photosensitivity: HCP is a condition related to sunlight. The porphyrins that accumulate when exposed to the sun cause extensive damage, including blisters and pain. 

 Neurological Symptoms: Changes in porphyrin may affect the nerve function of the central nervous system and result in problems such as abdominal discomfort, numbness, muscle weakness and mental conditions likely through effects on neurotoxicity and neurotransmitter function. 

Etiology

Hereditary Coproporphyria is mainly stimulated by mutations in the CPOX gene, which lead to the ineffective function of certain enzymes and the accumulation of their substrates. 

Factors like hormones, medicine, consumption of alcohol and triggering environment. Moreover, they tend to worsen the symptoms in the patients with HCP. These phases of the life cycle may cause the flaring-up of acute porphyria or worsen the disease (abdominal pain, neurological disturbances, and psychological symptoms). 

Genetics

Prognostic Factors

Genetic Mutation: Individuals having this mutation in the gene, which codes for porphobilinogen deaminase enzyme, may suffer more severely or have an adverse outcome. 
Age of Onset:  Individuals who had reached the initial stage of the disease, may be considered as the critical group since they are more likely to suffer from worse disease symptoms. 

Clinical History

Age group: Hereditary Coproporphyria typically manifests in adolescence or early adulthood, usually between the ages of 20 and 40. However, symptoms can appear at any age.

Physical Examination

Skin Changes 

Abdominal Tenderness 

Neurological Signs 

Mental Status Examination 

Vital Signs 

Age group

Associated comorbidity

Medications 

Alcohol 

Stress 

Hormonal Changes 

Associated activity

Acuity of presentation

Neurological Symptoms 
The main symptom is cramping  and pain accompanied by nausea, vomiting and constipation. 
Neuropsychiatric symptoms:  Hallucination and seizures as a result of Porphyrin accumulation. 
Peripheral neuropathy: Inability to control or coordinate the movement of the upper and lower limbs because of the nerve damage such as weakness or numbness and tingling. 
Cutaneous Symptoms: 
Photosensitivity: Having exposure to the sun leads to blistering, redness and itching because of the increased amount of skin becomes too pigmented. 
Hypertrichosis: The excessive hairiness on sun irradiated skin.  
Other Symptoms: 
Urinary symptoms: Green urine from porphyrin reddening. 
Gastrointestinal symptoms: Diarrhea, vomiting together with abdominal pain as the episode progresses. 

Differential Diagnoses

Acute Intermittent Porphyria  

Variegate Porphyria  

Guillain-Barre Syndrome 

Acute Pancreatitis 

Acute Cholecystitis 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Symptomatic management: 
Pain Management: Painkillers like opioids or NSAIDs (nonsteroidal anti-inflammatory drugs) could be used to reduce the severe pain that might occur during an acute attack. Nevertheless, it is necessary to exercise special caution when using opioids due to their potential respiratory depression. 
Nausea and Vomiting: Antiemetic drugs can be prescribed to help pregnant women reduce the feeling of sickness and vomiting. 
Hydration: IV fluids will be also be provided to prevent dehydration, if the patients suffering from vomiting. 
Heme Therapy: In extreme cases heme therapy through the veins is also necessary to minimize the concentration of porphyrin precursors and improve the patient’s condition. The heme iron or hematin is often used as a medium for these reactions. 
Preventive Measures: 
Avoiding Triggers: Known acute triggers should be avoided in order to  prevent from attacks. 
Regular Monitoring: Repeated scheduling with a healthcare professional to observe the symptoms and to modify the treatment when required. 
Sun Protection: Covering the hands and face with cotton clothes and glasses and by applying a sunscreen should be carried out to avoid the occurrence of any symptoms related to sun exposure.  
Medication Management: The precautionary approach in taking the drugs and updated health plan providers with this diagnosis to prevent from the medicines that can trigger an attack. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-hereditary-coproporphyria-specialty

Avoidance of Triggering Factors: Sleeping difficulties, stress and increased light sensitivity are some of the circumstances leading to worsening of HCP.  Check all triggers and try to avoid it. 
Sun Protection: Heats of the sun can cause intense reproach in the skin. Fabricating the protective set of clothes to include hats, sunglasses and applying the broad-range sunscreen will limit the impact of the sunlight on individuals with sensitive type. 
Medication Management: It is crucial for those who are diagnosed with HCP to interact constantly with medical professionals to confirm the medications which may aggravate the symptoms. 
Stress Management: Stress may be an added factor that has an aggravates the symptoms HCP. some stress restorative techniques like meditation, yoga, deep breathing exercises or therapy to help them beat stress and reduce the frequency of attacks. 

Effectiveness of blood products in treating Hereditary Coproporphyria

Panhematin: Panhematin (heme for injection) is a medication used to treat acute attacks of porphyria, including hereditary coproporphyria.

Use of GABA Analogs in Hereditary Coproporphyria

Gabapentin: A compound closely resembling the neurotransmitter GABA, yet lacking any impact on GABA binding, uptake, or degradation, has been identified. Research indicates the existence of gabapentin binding sites distributed throughout the brain. 

role-of-management-in-treating-hereditary-coproporphyria

Diagnosis: People can be diagnosed by using observation of symptoms, laboratory tests (biochemical) and genetic tests.

Avoid Triggers: Stay in control of conditions like alcohol, stress and certain medications.

Medications: Use hemetherapy for attacks and medications for the treatment.   

Nutrition: Utilise high-carb diet and avoid trigger foods.
Lifestyle: Change your lifestyle habits and manage your stress.

Monitoring: Regular porphyrin concentration and check liver performance.
Genetic Counseling: Understand inheritance and reproductive risks.
Patient Support: Educate patients and families on lifestyle and managing symptoms. 

Medication

Future Trends

Media Gallary

References

Hereditary Coproporphyria – GeneReviews® – NCBI Bookshelf (nih.gov)