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Hawkinsinuria(HWKS)

MedGen UID:
419319
Concept ID:
C2931042
Disease or Syndrome
Synonym: 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency
SNOMED CT: Hawkinsinuria (414380008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): HPD (12q24.31)
 
HPO: HP:0034457
Monarch Initiative: MONDO:0007700
OMIM®: 140350
Orphanet: ORPHA2118

Definition

Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000). [from OMIM]

Clinical features

From HPO
4-Hydroxyphenylpyruvic aciduria
MedGen UID:
376416
Concept ID:
C1848678
Finding
Increased relative concentration of 4-hydroxyphenylpyruvic acid in the urine.
4-hydroxyphenylacetic aciduria
MedGen UID:
376417
Concept ID:
C1848680
Finding
Increased concentration of 4-hydroxyphenylacetic acid in the urine.
Hawkinsinuria
MedGen UID:
419319
Concept ID:
C2931042
Disease or Syndrome
Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000).
Elevated urine hydroxyphenyllactic acid level
MedGen UID:
1054289
Concept ID:
CN378356
Finding
The amount of hydroxyphenyllactic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Restlessness
MedGen UID:
854457
Concept ID:
C3887611
Sign or Symptom
A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Hypertyrosinemia
MedGen UID:
742296
Concept ID:
C1879362
Disease or Syndrome
An increased concentration of tyrosine in the blood.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHawkinsinuria
Follow this link to review classifications for Hawkinsinuria in Orphanet.

Conditions with this feature

Hawkinsinuria
MedGen UID:
419319
Concept ID:
C2931042
Disease or Syndrome
Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000).

Professional guidelines

Recent clinical studies

Etiology

Wojtowicz P, Zrostlíková J, Kovalczuk T, Schůrek J, Adam T
J Chromatogr A 2010 Dec 17;1217(51):8054-61. Epub 2010 Oct 1 doi: 10.1016/j.chroma.2010.09.067. PMID: 20961553
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Diagnosis

Zhao D, Tian Y, Li X, Ni M, Zhu X, Jia L
J Pediatr Endocrinol Metab 2020 Apr 28;33(4):563-567. doi: 10.1515/jpem-2019-0498. PMID: 32109208
Cruz-Camino H, Vazquez-Cantu DL, Zea-Rey AV, López-Valdez J, Jiménez-Lozano J, Gómez-Gutiérrez R, Cantú-Reyna C
J Int Med Res 2020 Feb;48(2):300060519863543. Epub 2019 Jul 25 doi: 10.1177/0300060519863543. PMID: 31342835Free PMC Article
Peters V, Bonham JR, Hoffmann GF, Scott C, Langhans CD
J Inherit Metab Dis 2016 Sep;39(5):683-687. Epub 2016 May 4 doi: 10.1007/s10545-016-9941-1. PMID: 27146437
Brownlee JM, Heinz B, Bates J, Moran GR
Biochemistry 2010 Aug 24;49(33):7218-26. doi: 10.1021/bi1008112. PMID: 20677779
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Therapy

Gomez-Ospina N, Scott AI, Oh GJ, Potter D, Goel VV, Destino L, Baugh N, Enns GM, Niemi AK, Cowan TM
J Inherit Metab Dis 2016 Nov;39(6):821-829. Epub 2016 Aug 3 doi: 10.1007/s10545-016-9963-8. PMID: 27488560

Prognosis

Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F
Mol Genet Metab 2000 Nov;71(3):506-10. doi: 10.1006/mgme.2000.3085. PMID: 11073718
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Clinical prediction guides

Brownlee JM, Heinz B, Bates J, Moran GR
Biochemistry 2010 Aug 24;49(33):7218-26. doi: 10.1021/bi1008112. PMID: 20677779
Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F
Mol Genet Metab 2000 Nov;71(3):506-10. doi: 10.1006/mgme.2000.3085. PMID: 11073718

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