ALAD Deficiency Diagnosis and Management

Clinical Significance

Deficiency of ALAD leads to ALAD porphyria (ALAD-P), one of the acute hepatic porphyrias (AHPs), characterized by extremely rare autosomal recessive disorder with fewer than a dozen reported cases worldwide 1, 2
ALAD porphyria is distinguished from other acute hepatic porphyrias by elevated ALA in urine without elevated PBG 1, 2

In ALAD porphyria, diagnosis can be confirmed by genetic testing for pathogenic variants in the ALAD gene, and clinicians should check lead levels and urine organic acids to rule out lead poisoning and hereditary tyrosinemia 1, 2, 3, 4
Elevated ALA in urine (without elevated PBG) is a key diagnostic feature of ALAD porphyria, according to the American Gastroenterological Association 3, 4

ALAD deficiency presents with acute neurovisceral symptoms similar to other acute hepatic porphyrias, including severe abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension 1, 2
Treatment of acute attacks in ALAD porphyria includes discontinuation of porphyrinogenic drugs and chemicals, administration of intravenous dextrose and hemin, and use of analgesics and antiemetics, as recommended by the American Gastroenterological Association 1, 2

Patients with ALAD deficiency require regular monitoring of liver enzymes, creatinine and eGFR, blood pressure, symptoms of neuropathy, and screening for hepatocellular carcinoma in appropriate cases, according to the American Gastroenterological Association 3, 4, 5
Long-term monitoring is essential due to potential complications including chronic kidney disease, hypertension, and hepatocellular carcinoma 3, 5