Histidinemia is a rare genetic disorder characterized by abnormal metabolism and accumulation of the amino acid histidine in the blood and urine.
Presentation
A deficiency of the enzyme histidase, needed for the metabolism of histidine, results in an abnormal accumulation of histidine in the serum as well as its increased excretion in the urine. Most patients however, adapt to the increased levels of histidine and live a normal life without many symptoms.
This rare disease, with an autosomal recessive mode of inheritance, was originally linked to multiple developmental disorders [1]. For many years, histidinemia was considered to be responsible for neurological symptoms such as hydrocephalus, cerebellar ataxia, seizures, emotional disturbances as well as certain non-neurological features that include multiple congenital anomalies, aplastic anemia, idiopathic thrombocytopenic purpura, growth retardation, precocious puberty and recurrent infections. Multiple studies conducted since have rejected this hypothesis, noting these findings to be coincidental [2] [3].
Histidinemia is now thought to be a benign inborn error of metabolism with the majority of patients being asymptomatic, with normal speech and mental development. However, clinical symptoms are seen in some patients and studies in newborns now consider histidinemia to be a risk factor for neurological impairment. These findings were seen to be more common in those with an adverse perinatal history [4] [5].
Atypical histidinemia is a milder form of this disorder and is seen in a minority of cases. As compared to patients with classical histidinemia, these patients usually show higher cutaneous levels of the enzyme, histidase and lower serum levels of histidine. Being clinically asymptomatic, these cases serve to illustrate the biochemical and genetic heterogeneity of histidinemia [6] [7].
Women with histidinemia deliver babies who usually do not suffer from any residual abnormalities [8].
Entire Body System
- Developmental Disorder
However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events. [cags.org.ae]
Histidase is needed for the metabolism of the amino acid histidine.[1] Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder,[2] leading to a reduction in the prevalence [wikiwand.com]
Journal of Autism and Developmental Disorders, v9 n1 p55-60 Mar 1979 The article presents a case history of a boy with both infantile autism and histidenia (an inborn error of amino acid metabolism), and discusses the possible relationship between the [eric.ed.gov]
disorders 1979 A 10-year-old boy first showed features of infantile autism at age 24 months. [semanticscholar.org]
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). [ncbi.nlm.nih.gov]
- Pallor
[…] tetrahydrobiopterin deficiency If phenylalanine levels are decreased: BH4 deficiency If phenylalanine levels remain unchanged: PAH deficiency [25] ↑ Phenylketones in urine Hyperphenylalaninemia Pathology: shows abnormal myelination in affected individuals [26] Pallor [amboss.com]
Respiratoric
- Delayed Speech Development
Symptoms include organic acids in urine, mental retardation, and delayed speech development. Treatment includes a low-histamine diet. [smpdb.ca]
Skin
- Fair Complexion
Growth restriction Psychomotor delay (starting as early as 4–6 months of age) Seizures [24] Blue eyes, light, pale hair (fair complexion) Eczema Musty odor (due to an increase in aromatic amino acids) Infants with maternal PKU may show Diagnostics Newborn [amboss.com]
Psychiatrical
- Behavior Disorder
Urea cycle disorders OTC deficiency is the only urea cycle disorder that is X-linked recessive. All other urea cycle disorders are autosomal recessive. [amboss.com]
Urogenital
- Phenylketonuria
Of 34.5 million babies tested for phenylketonuria, 3000 cases have been diagnosed in time to prevent mental retardation by means of dietary therapy. [books.google.ro]
Abstract As a result of mass testing for phenylketonuria in infants and retarded children with the urinary ferric chloride test, a new entity, histidinemia, was described by Ghadimi and associates in 1961. [annals.org]
Imidazolepyruvic acid in the urine of these patients gives a green color with ferric chloride, and the disease may be confused with phenylketonuria. Patients with histidinemia lack urocanic acid in the skin and sweat. [pediatrics.aappublications.org]
Phenylketonuria (PKU) Defect: Phe Hydroxylase Phenylalanine (Phe) normal Phe Hydroxylase (PheH): makes DoPA -->to Melanin [Phe ---(PheH)> tyrosine (using NADPH, and O2) (release H2O, NADP+) Tyrosine ---(Tyr.H) --> 3,4,Dihydroxy-Phe --->->-> Melanin] a [quizlet.com]
الصفحات المحددة صفحة العنوان جدول المحتويات فهرس المراجع المحتويات RECOMMENDATIONS 1 Definition 9 SCREENING FOR PHENYLKETONURIA 21 The Development of Legislation 44 Lessons Learned from the pku Experience 88 SCREENING FOR OTHER DISEASES 95 Secretary of [books.google.com]
Neurologic
- Speech Disorder
[Full text - PDF] ABSTRACT Histidinemia is one of the most frequent innate errors during childhood with a prevalence of nearly 1:15 000, speech disorder being its more remarkable result. [new.medigraphic.com]
Full text ABSTRACT Histidinemia is one of the most frequent innate errors during childhood with a prevalence of nearly 1:15 000, speech disorder being its more remarkable result. [medigraphic.com]
For years, intellectual disability and speech disorders were associated with histidinemia. [rarediseases.org]
- Average Intelligence
Two of them were also entirely normal in intelligence and language. One child with low average intelligence and emotional immaturity manifested im- mature use of syntax on language evalua- R.G. I T.L. 100 I 100 I I normal I abnormal 50 I 94 ~ C. [docslide.com.br]
Workup
Many congenital disorders were attributed to histidinemia in the past and neonatal screening programs were initiated in many countries to detect the same. However, multiple research studies over the years have refuted this linkage and screening programs performed on neonates have, therefore, been scrapped [9].
Histidinemia can be diagnosed by the presence of increased levels of histidine in the blood and urine. In addition, the levels of histamine and imidazole pyruvic acid may also be elevated. On the other hand, products resulting from the metabolism of histidine, such as urocanic acid, are decreased in the blood, urine, and skin cells. The normal blood levels of histidine lie in the range of 70 to 120 μM/l, with values above 290 μM/l being considered abnormally high [10].
Increased levels of histidine and histamine are also observed in the cerebrospinal fluid. The residual histidase activity per gram tissue of skin is decreased in patients with histidinemia.
Patients with atypical histidinemia show less pronounced elevation in the serum and urine histidine levels as well as in the cutaneous histidase activity.
Treatment
In most individuals with histidinemia, the condition is clinically silent and considered benign, with no need for treatment or a specific diet. [orpha.net]
Treatment Dietary treatment based on low-histidine lowers the blood histidine level. Symptoms and Signs Though it may remain asymptomatic for a few years, symptoms will typically present by early childhood. [medigest.uk]
There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]
Prognosis
Prognosis The life expectancy is not affected. Patients with histidinemia show good prognosis. The documents contained in this web site are presented for information purposes only. [orpha.net]
Close inquiries should be made about the benefit of such a dietary regimen and the long term prognosis therewith. A screening test for homocystinuria by the detection of blood methionine level is difficult. [doi.org]
Historical Perspective Classification Pathophysiology Causes Differentiating Histidinemia from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria History and [wikidoc.org]
Etiology
Etiology Histidinemia is caused by impaired conversion of histidine to urocanic acid via the histidase enzyme. Deficiency in this enzyme is related to mutations in the histidine ammonia-lyase HAL gene (12q22-q24.1). [orpha.net]
The etiology of this malformation is discussed in relation to histidinemia and the family history of neurologic disorder. Accepted November 30, 1967. [pediatrics.aappublications.org]
Epidemiology
Summary Epidemiology Reported prevalence varies widely from 1/8,600 to 1/180,000, probably as a result of differing screening programs. [orpha.net]
Historical Perspective Classification Pathophysiology Causes Differentiating Histidinemia from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria History and [wikidoc.org]
Epidemiology Etiology: caused by defects in mitochondrial DNA, which are maternally inherited General pathophysiology Clinical features Diagnostics Genetic studies (including mitochondrial DNA) Muscle biopsy: Immunohistochemistry typically shows ragged [amboss.com]
Pathophysiology
The pathophysiology of neurological disorders in childhood is based on the same principles of the organization, structure, and function of the nervous sys tem as apply to adults. Two pitfalls are present for the student, however. [books.google.com]
Epidemiology Etiology: caused by defects in mitochondrial DNA, which are maternally inherited General pathophysiology Clinical features Diagnostics Genetic studies (including mitochondrial DNA) Muscle biopsy: Immunohistochemistry typically shows ragged [amboss.com]
Historical Perspective Classification Pathophysiology Causes Differentiating Histidinemia from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria History and [wikidoc.org]
The Journal of allergy and clinical immunology. 1990 Oct [PubMed PMID: 1699987] [10] Schubert ML, Physiologic, pathophysiologic, and pharmacologic regulation of gastric acid secretion. [statpearls.com]
Prevention
Of 34.5 million babies tested for phenylketonuria, 3000 cases have been diagnosed in time to prevent mental retardation by means of dietary therapy. [books.google.ro]
[…] of Histidinemia No, it is not possible to prevent Histidinemia. autosomal recessive disorder Occurrence of Histidinemia Number of Cases The following are the number of Histidinemia cases seen each year worldwide: Rare between 10K - 50K cases Common Age [tabletwise.net]
In the case of histidinemia, the U.S. was focused on the prevention, as well as social and personal costs, of intellectual disabilities due to numerous political factors. [rwjf.org]
Japan Search for more papers by this author First published: September 1981 Summary A program of newborn mass screening for inborn errors of metabolism has since 1977 been conducted by The Ministry of Health and Welfare in Japan with great success in preventing [doi.org]
References
- Taylor RG, Levy HL, McInnes RR. Histidase and histidinemia. Clinical and molecular considerations. Mol Biol Med. 1991 Feb;8(1):101-16.
- Lam WK, Cleary MA, Wraith JE, Walter JH. Histidinaemia: a benign metabolic disorder. Arch Dis Child 1996;74:343-346.
- Kawai Y, Moriyama A, Asai K, et al. Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene. Hum Genet. 2005 Apr;116(5):340-6.
- Scriver CR, Levy HL. Histidinaemia. Part I: Reconciling retrospective and prospective findings. J Inherit Metab Dis. 1983;6(2):51-3.
- Khanna R, Chang TM. Characterization of L-histidine ammonia-lyase immobilized by microencapsulation in artificial cells: preparation, kinetics, stability, and in vitro depletion of histidine. Int J Artif Organs, 1990; 13:189-95.
- Suchi M, Sano H, Mizuno H, Wada Y. Molecular cloning and structural characterization of the human histidase gene (HAL). Genomics. 1995 Sep 1;29(1):98-104.
- Schwede TF, Rétey J, Schulz GE. Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile. Biochemistry. 1999 Apr 27;38(17):5355-61.
- Levy HL. Disorders of histatidine metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic Basis of Inherited Disease. 6th ed. New York, McGraw-Hill, 1989; p563.
- Kitagawa T, Owada M, Sakiyama T, Kojima T, Kondo T (1981). "Experience and problems of newborn mass screening for inborn errors of metabolism in Japan". Acta Paediatr. Jpn. 1981;23 (1): 24–34.
- Kopple JD, Swendseid ME. Evidence that histidine is an essential amino acid in normal and chronically uremic man. J Clin Invest. 1975 May;55(5):881-91.