Patient Overview
A 71-year-old woman presented with diffuse abdominal discomfort and bloating for three years, accompanied by insomnia. Evaluation at a local hospital resulted in a diagnosis of anxiety disorder, and treatment with a sedative–hypnotic agent and a selective serotonin reuptake inhibitor was initiated. However, abdominal discomfort persisted and recurred, resulting in ten subsequent hospitalizations.
The patient had a 30-year history of diabetes mellitus. Oral hypoglycemic agents were used initially, but insulin therapy was initiated 14 years earlier because glycemic control remained inadequate. Eight years before the current admission, distal numbness and intermittent foot spasms developed, leading to a diagnosis of diabetic peripheral neuropathy.
Current Clinical Presentation
During the present hospitalization, the patient reported persistent abdominal distension and generalized abdominal pain, with a Numeric Rating Scale (NRS) score of 2. The symptoms were accompanied by muscle weakness.
Psychiatric manifestations had worsened compared with previous episodes and included depressed mood, diminished interest, anxiety, excessive worry, rapid heartbeat, chest tightness, occasional feelings of impending doom, and poor sleep.
Laboratory testing demonstrated a fasting blood glucose level of 6.52 mmol/L (reference range 3.9-6.1 mmol/L, glucose oxidase method). Urine ketones were negative, excluding diabetic ketoacidosis.
Diagnostic Evaluation
Extensive investigations did not identify a structural gastrointestinal cause for the recurrent symptoms. Abdominal ultrasonography and computed tomography showed no gallbladder stones, cholecystitis, common bile duct stones, gastrointestinal perforation, acute pancreatitis, intra-abdominal abscess, mesenteric artery occlusion, or intestinal obstruction. Endoscopic examination of the stomach, duodenum, and colon revealed no ulcers, tumors, ischemia, bleeding, or inflammatory lesions.
Laboratory investigations are summarized in Table 1.
Table 1. Laboratory Investigations
Test | Result | Reference Range |
|---|---|---|
WBC | 6.3 ×10⁹/L | 3.5-9.5 ×10⁹/L |
EO | 0.02 ×10⁹/L | 0.02-0.52 ×10⁹/L |
CRP | 10.1 mg/L | 0-10 mg/L |
TBIL | 12.2 μmol/L | ≤23.0 μmol/L |
AMY | 32 U/L | 35-135 U/L |
Creatinine | 55 μmol/L | 41-81 μmol/L |
D-dimer | 0.91 mg/L | 0–0.60 mg/L |
Blood lead | 26.9 μg/L | <200 μg/L |
Sodium | 144 mmol/L | 135-145 mmol/L |
Abbreviations: WBC, white blood cell; EO, eosinophil; CRP, C-reactive protein; TBIL, total bilirubin; AMY, amylase.
The coexistence of abdominal discomfort, fatigue, neuropsychiatric manifestations, and peripheral neuropathy in the absence of structural gastrointestinal disease raised suspicion for acute hepatic porphyria.
Quantitative urinary porphobilinogen (PBG) testing was unavailable. A non-standardized sunlight exposure test was therefore used as an initial screening method. Following sunlight exposure, the urine changed color from yellow to wine red. This method is neither sensitive nor specific for variegate porphyria and cannot differentiate among porphyria types. The finding served only to raise clinical suspicion and supported referral for genetic analysis.
Genetic testing identified a heterozygous variant in the protoporphyrinogen oxidase (PPOX) gene, establishing the diagnosis of variegate porphyria.
Table 2. Genetic Findings
Parameter | Finding |
|---|---|
Gene | PPOX |
Chromosomal location | chr1:161138317 (GRCh37/hg19) |
Transcript | NM_001122764.3 |
Exon | 6 of 13 |
Variant | c.567A>C |
Protein change | p.Gln189His |
Amino acid substitution | Glutamine → Histidine (codon 189) |
Classification | Pathogenic (ClinVar) |
Bidirectional Sanger sequencing in forward and reverse directions confirmed the heterozygous state of the variant. The mutation is extremely rare in population databases (gnomAD frequency 0.00000398). In-silico prediction tools, including PolyPhen-2, SIFT, and CADD, support a deleterious functional effect. The variant has previously been reported in individuals with variegate porphyria.
Severity assessment showed serum sodium of 144 mmol/L, excluding hyponatremia. Abdominal pain remained mild and was not associated with nausea, vomiting, ileus, autonomic instability, or progressive neurological deficits. The absence of severe pain, autonomic instability, hyponatremia, and neurologic red flags supported the classification of the episode as a mild acute attack.
Management
- Intravenous infusion of 10%-20% glucose solution dissolved in saline was administered because intravenous hemin therapy was unavailable, with proportional insulin adjustment.
- Carbohydrate loading suppressed hepatic aminolevulinic acid synthase-1 (ALAS1) activity and reduced accumulation of neurotoxic heme precursors.
- Lorazepam 1 mg once daily was administered to improve anxiety and sleep disturbance.
- Paroxetine 10 mg once daily was initiated for antidepressant therapy.
- Fasting blood glucose levels were maintained at 8-9 mmol/L during hospitalization to prevent symptom exacerbation associated with caloric or carbohydrate restriction.
Follow-Up
- Abdominal pain improved within 24-48 hours after initiation of intravenous glucose therapy.
- Neuropsychiatric symptoms, including anxiety, depressed mood, and insomnia, gradually improved over the following days.
- Education emphasized the importance of adequate caloric intake in preventing porphyric attacks.
- Follow-up counseling included adjustments to fasting blood glucose monitoring thresholds in the context of diabetes management.
- At three-month and six-month follow-up, abdominal pain episodes decreased substantially and psychiatric symptoms improved, with recurrence no more than once per month.
