IEMbase 0045: HAL-related histidine ammonia-lyase deficiency

Scope

Field	Value
IEMbase ID	45
Nosology	1.10.01.01
Gene	HAL
External IDs	OMIM:235800
Generated mapping	UNMAPPED
Candidate DisMech targets	None; fuzzy neighbor 3-Hydroxy-3-Methylglutaric_Aciduria.yaml
Review date	2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive HAL-related histidine ammonia-lyase deficiency, also named histidase deficiency or histidinemia. The reported prevalence varies between 1:8,600 and 1:180,000, and treatability is unknown.

The biochemical signature is increased histidine in CSF, plasma, and urine, decreased fibroblast histidase activity, increased urinary imidazole pyruvic acid, and urinary ketones from later childhood onward. The characteristic clinical block records no clinical significance. IEMbase lists no treatments.

DisMech phenotype coverage

There is no local DisMech entry for HAL deficiency, histidase deficiency, or histidinemia.

The fuzzy neighbor 3-Hydroxy-3-Methylglutaric_Aciduria.yaml is a false positive. That entry is HMGCL deficiency, a ketogenesis and leucine degradation disorder with hypoketotic hypoglycemia, organic acid accumulation, metabolic acidosis, and hyperammonemia. It does not model HAL, histidase, histidine catabolism, or imidazole pyruvate.

Concordance and completeness

Judgement: true unmapped record. The local knowledge base has no disease-level target for benign histidinemia.

The shared keyword "aciduria" and the presence of ketone language are not enough to map HAL deficiency to HMGCL deficiency. The genes, pathway, biomarkers, and clinical risk profile are different.

Curation actions

• Keep the record unmapped.
• Do not map to HMGCL deficiency or other organic acidurias based on superficial aciduria/ketone overlap.
• If curated later, represent the HAL/histidase enzymatic block and the high-histidine plus imidazole-pyruvate biochemical profile, with the benign clinical interpretation preserved unless stronger evidence is added.