A novel heterozygous mutation in the hydroxymethylbilane synthase gene in a case with acute intermittent porphyria

Abstract

Porphyrias are rare metabolic disorders caused by inherited or acquired enzymatic defects in the heme biosynthetic pathway. They are grouped into acute hepatic porphyrias and photocutaneous porphyrias. Acute intermittent porphyria, the most prevalent subtype of acute hepatic porphyrias, is caused by a mutation in the hydroxymethylbilane synthase gene. In this work, a case of a 13 year-old Indian female presenting with multi-organ involvement (Neurological: episodic seizures, behavioral abnormalities, acute onset progressive flaccid-motor quadriparesis, multiple cranial nerve palsies, respiratory paralysis, dysautonomia, and posterior reversible encephalopathy syndrome; Gastrointestinal: recurrent attacks of abdominal pain, nausea/vomiting, isolated transaminitis, and acute pancreatitis; and Renal: metabolic alkalosis and refractory dyselectrolytemia) which resulted in significant diagnostic dilemmas. She was eventually diagnosed as a case of acute intermittent porphyria harboring a novel hydroxymethylbilane synthase gene mutation (p.Arg173Trp).

A Novel Adult Case of Recurrent Acute Pancreatitis Caused by Hypercalcemia With Concurrent Manifestation of Posterior Reversible Encephalopathy Syndrome Revealing Undiagnosed Primary Hyperparathyroidism due to an Underlying Parathyroid Adenoma

“…[1][2][3][4][5][6][9][10][11][12][13][14][15] The presence of hemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are all congruent with the diagnosis of PRES. [1][2][3][4][5][6][9][10][11][12][13][14][15] PRES might cause substantial morbidity and even mortality in severe forms, most often because of acute hemorrhage or massive posterior fossa edema triggering obstructive hydrocephalus or brainstem compression. 9 In most cases, PRES resolves spontaneously, but treatment can be challenging and should be initiated early to reduce potential morbidity and mortality.…”

“…1 Endothelial dysfunction is a critical factor in the underlying pathophysiology of PRES resulting from abrupt changes in blood pressure or direct toxic effects of cytokines that lead to the breakdown of the blood-brain barrier and brain edema. [1][2][3][4][5][6][9][10][11][12][13][14][15] PRES should be considered in patients with acute neurological symptoms, arterial hypertension, renal failure, autoimmune disease, immunosuppressive therapy or chemotherapy, preeclampsia/eclampsia, severe dysautonomia, and infections. [1][2][3][4][5][6][9][10][11][12][13][14][15] It commonly appears with altered consciousness, seizures, headache, visual disturbances, and, rarely, focal neurological deficits.…”

“…[1][2][3][4][5][6][9][10][11][12][13][14][15] PRES should be considered in patients with acute neurological symptoms, arterial hypertension, renal failure, autoimmune disease, immunosuppressive therapy or chemotherapy, preeclampsia/eclampsia, severe dysautonomia, and infections. [1][2][3][4][5][6][9][10][11][12][13][14][15] It commonly appears with altered consciousness, seizures, headache, visual disturbances, and, rarely, focal neurological deficits. [1][2][3][4][5][6][9][10][11][12][13][14][15] Brain MRI can confirm the edema, which often involves, but is not solely restricted to, parieto-occipital cortical and subcortical structures that resolve within days or weeks.…”

“…[1][2][3][4][5][6][9][10][11][12][13][14][15] It commonly appears with altered consciousness, seizures, headache, visual disturbances, and, rarely, focal neurological deficits. [1][2][3][4][5][6][9][10][11][12][13][14][15] Brain MRI can confirm the edema, which often involves, but is not solely restricted to, parieto-occipital cortical and subcortical structures that resolve within days or weeks. [1][2][3][4][5][6][9][10][11][12][13][14][15] The presence of hemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are all congruent with the diagnosis of PRES.…”

“…[1][2][3][4][5][6][9][10][11][12][13][14][15] Brain MRI can confirm the edema, which often involves, but is not solely restricted to, parieto-occipital cortical and subcortical structures that resolve within days or weeks. [1][2][3][4][5][6][9][10][11][12][13][14][15] The presence of hemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are all congruent with the diagnosis of PRES. [1][2][3][4][5][6][9][10][11][12][13][14][15] PRES might cause substantial morbidity and even mortality in severe forms, most often because of acute hemorrhage or massive posterior fossa edema triggering obstructive hydrocephalus or brainstem compression.…”