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Histidinemia

MedGen UID:
113135
•Concept ID:
C0220992
•
Disease or Syndrome
Synonyms: Deficiency of histidine ammonia-lyase; HAL deficiency; HIS deficiency; Histidase deficiency; Histidine ammonia-lyase deficiency; Hyperhistidinemia
SNOMED CT: Deficiency of histidine a-deaminase (124628005); Deficiency of histidinase (124628005); Deficiency of histidase (124628005); Deficiency of histidine ammonia-lyase (124628005); Histidinemia (410058007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): HAL (12q23.1)
 
HPO: HP:0010906
Monarch Initiative: MONDO:0009345
OMIM®: 235800
Orphanet: ORPHA2157

Definition

Histidinemia is a metabolic disorder characterized by increased levels of histidine in blood, urine, and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. Although histidinemia was originally associated with mental retardation and speech defects, it is generally considered to be a benign disorder (Levy et al., 2001). However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events (Ishikawa, 1987). [from OMIM]

Additional description

From MedlinePlus Genetics
Histidinemia is an inherited condition characterized by elevated levels of histidine in blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). Histidine is an amino acid that acts as a building block for many different proteins. 

In most cases, histidinemia does not cause health problems. Most people with elevated histidine levels are unaware that they have this condition. Rarely, people with histidinemia have intellectual disabilities, learning disabilities, or behavioral problems. Having a medical complication during or soon after birth might increase the risk of developmental problems in people with histidinemia.   https://medlineplus.gov/genetics/condition/histidinemia

Clinical features

From HPO
Histidinuria
MedGen UID:
1731918
•Concept ID:
C5399766
•
Finding
An increased concentration of histidine in the urine.
See: Feature record | Search on this feature
Elevated urinary N-tau-ribosylhistidine level
MedGen UID:
1054185
•Concept ID:
CN377453
•
Finding
Presence of N tau-ribosylhistidine (His-R) in the urine. His-R is a histidine derivative found in the urine of histidinemic patients.
See: Feature record | Search on this feature
Intellectual disability
MedGen UID:
811461
•Concept ID:
C3714756
•
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
See: Feature record | Search on this feature
Histidinemia
MedGen UID:
113135
•Concept ID:
C0220992
•
Disease or Syndrome
Histidinemia is a metabolic disorder characterized by increased levels of histidine in blood, urine, and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. Although histidinemia was originally associated with mental retardation and speech defects, it is generally considered to be a benign disorder (Levy et al., 2001). However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events (Ishikawa, 1987).
See: Feature record | Search on this feature
Show allHide all

Conditions with this feature

Histidinemia
MedGen UID:
113135
•Concept ID:
C0220992
•
Disease or Syndrome
Histidinemia is a metabolic disorder characterized by increased levels of histidine in blood, urine, and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. Although histidinemia was originally associated with mental retardation and speech defects, it is generally considered to be a benign disorder (Levy et al., 2001). However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events (Ishikawa, 1987).
See: Condition Record
Histidinemia

Professional guidelines

PubMed

Newborn screening for inborn errors of metabolism in Japan. A history of the development of newborn screening.
Kitagawa T
Pediatr Endocrinol Rev 2012 Oct;10 Suppl 1:8-25. PMID: 23330242
The lure of treatment: expanded newborn screening and the curious case of histidinemia.
Brosco JP, Sanders LM, Dharia R, Guez G, Feudtner C
Pediatrics 2010 Mar;125(3):417-9. Epub 2010 Feb 15 doi: 10.1542/peds.2009-2060. PMID: 20156889
Newborn screening in Japan.
Aoki K
Southeast Asian J Trop Med Public Health 2003;34 Suppl 3:80. PMID: 15906702

Recent clinical studies

Etiology

Newborn screening for inborn errors of metabolism in Japan. A history of the development of newborn screening.
Kitagawa T
Pediatr Endocrinol Rev 2012 Oct;10 Suppl 1:8-25. PMID: 23330242
Long-term follow-up of 58 patients with histidinemia treated with a histidine-restricted diet: no effect of therapy.
Widhalm K, Virmani K
Pediatrics 1994 Dec;94(6 Pt 1):861-6. PMID: 7971002
Hyperhistaminemia in patients with histidinemia due to increased decarboxylation of histidine.
Tanabe M, Sakura N
Clin Chim Acta 1989 Dec 29;186(1):11-7. doi: 10.1016/0009-8981(89)90197-6. PMID: 2482142
Zinc status of untreated histidinemic children.
Kitano A, Higashi A, Nagata N, Matsuda I, Hase Y, Oura T
J Pediatr Gastroenterol Nutr 1985 Oct;4(5):752-5. doi: 10.1097/00005176-198510000-00012. PMID: 3930685
The nutritional therapy of histidinemia.
Snyderman SE, Sansaricq C, Norton PM, Manka M
J Pediatr 1979 Nov;95(5 Pt 1):712-5. doi: 10.1016/s0022-3476(79)80716-7. PMID: 490237

Diagnosis

Nano optical probe samarium tetracycline complex for early diagnosis of histidinemia in new born children.
Attia MS
Biosens Bioelectron 2017 Aug 15;94:81-86. Epub 2017 Feb 14 doi: 10.1016/j.bios.2017.02.018. PMID: 28262611
Newborn screening in Japan.
Aoki K
Southeast Asian J Trop Med Public Health 2003;34 Suppl 3:80. PMID: 15906702
Histidinemia: a biochemical variant or a disease?
Virmani K, Widhalm K
J Am Coll Nutr 1993 Apr;12(2):115-24. doi: 10.1080/07315724.1993.10718291. PMID: 8463510
Histidinemia and infantile autism.
Kotsopoulos S, Kutty KM
J Autism Dev Disord 1979 Mar;9(1):55-60. doi: 10.1007/BF01531292. PMID: 438113
Histidinemia and atopic dermatitis.
Arch Dermatol 1968 Sep;98(3):317-9. doi: 10.1001/archderm.98.3.317. PMID: 4299846

Therapy

Metabolic approaches to the treatment of autism spectrum disorders.
Page T
J Autism Dev Disord 2000 Oct;30(5):463-9. doi: 10.1023/a:1005563926383. PMID: 11098885
Long-term follow-up of 58 patients with histidinemia treated with a histidine-restricted diet: no effect of therapy.
Widhalm K, Virmani K
Pediatrics 1994 Dec;94(6 Pt 1):861-6. PMID: 7971002
Histidinuria: defective transport of histidine.
Nyhan WL, Hilton S
Am J Med Genet 1992 Nov 15;44(5):558-61. doi: 10.1002/ajmg.1320440505. PMID: 1481808
The nutritional therapy of histidinemia.
Snyderman SE, Sansaricq C, Norton PM, Manka M
J Pediatr 1979 Nov;95(5 Pt 1):712-5. doi: 10.1016/s0022-3476(79)80716-7. PMID: 490237
Infantile spasms associated with histidinemia.
Duffner PK, Cohen ME
Neurology 1975 Feb;25(2):195-7. doi: 10.1212/wnl.25.2.195. PMID: 1167649

Prognosis

Newborn screening for inborn errors of metabolism in Japan. A history of the development of newborn screening.
Kitagawa T
Pediatr Endocrinol Rev 2012 Oct;10 Suppl 1:8-25. PMID: 23330242
Lessons from the past--looking to the future. Newborn screening.
Levy HL
Pediatr Ann 2003 Aug;32(8):505-8. doi: 10.3928/0090-4481-20030801-07. PMID: 12942892
Long-term follow-up of 58 patients with histidinemia treated with a histidine-restricted diet: no effect of therapy.
Widhalm K, Virmani K
Pediatrics 1994 Dec;94(6 Pt 1):861-6. PMID: 7971002
Follow-up study of a nation-wide neonatal metabolic screening program in Japan. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan.
Tada K, Tateda H, Arashima S, Sakai K, Kitagawa T, Aoki K, Suwa S, Kawamura M, Oura T, Takesada M
Eur J Pediatr 1984 Aug;142(3):204-7. doi: 10.1007/BF00442450. PMID: 6468444
The nutritional therapy of histidinemia.
Snyderman SE, Sansaricq C, Norton PM, Manka M
J Pediatr 1979 Nov;95(5 Pt 1):712-5. doi: 10.1016/s0022-3476(79)80716-7. PMID: 490237

Clinical prediction guides

The self-assembly of L-histidine might be the cause of histidinemia.
Ajikumar A, Premkumar AKN, Narayanan SP
Sci Rep 2023 Oct 14;13(1):17461. doi: 10.1038/s41598-023-44749-5. PMID: 37838762Free PMC Article
Lessons from the past--looking to the future. Newborn screening.
Levy HL
Pediatr Ann 2003 Aug;32(8):505-8. doi: 10.3928/0090-4481-20030801-07. PMID: 12942892
Histidinemia: a biochemical variant or a disease?
Virmani K, Widhalm K
J Am Coll Nutr 1993 Apr;12(2):115-24. doi: 10.1080/07315724.1993.10718291. PMID: 8463510
Zinc status of untreated histidinemic children.
Kitano A, Higashi A, Nagata N, Matsuda I, Hase Y, Oura T
J Pediatr Gastroenterol Nutr 1985 Oct;4(5):752-5. doi: 10.1097/00005176-198510000-00012. PMID: 3930685
Geographical variations in inborn errors of metabolism in Japan.
Yasuda N
Hum Hered 1984;34(1):1-8. doi: 10.1159/000153410. PMID: 6735410

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