Hawkinsinuria - Misplaced Pages

(Redirected from 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency) Medical condition

Hawkinsinuria
Other names	4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency

Hawkinsin
Specialty	Endocrinology

Hawkinsinuria is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine.

Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).

Patients present with metabolic acidosis during the first year of life, and growth arrest around the time of weaning off breast milk. Treatment involves a diet containing a low amount of phenylalanine and tyrosine. Tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition. Patients have a normal life and do not require treatment or a special diet.

The production of hawkinsin is the result of a gain-of-function mutation. Inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). The gene affected is the HPD gene encoding 4-hydroxyphenylpyruvic acid dioxygenase, on chromosome 12q24. It is unusual in that most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).

References

Danks, D. M.; Tippett, P; Rogers, J (1975). "A new form of prolonged transient tyrosinemia presenting with severe metabolic acidosis". Acta Paediatr. Scand. 64 (2): 209–214. doi:10.1111/j.1651-2227.1975.tb03823.x. PMID 1130176. S2CID 28981382.
Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F (2000). "Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria". Mol Genet Metab. 71 (3): 506–510. doi:10.1006/mgme.2000.3085. PMID 11073718.
Niederwieser, A.; Matasovic, A.; Tippett, P.; Danks, D.M. (1977). "A new sulfur amino acid, named Hawkinsin, identified in a baby with transient tyrosinemia and her mother". Clin. Chim. Acta. 76 (3): 345–356. doi:10.1016/0009-8981(77)90161-9. PMID 858207.
^ McKusick, Victor A.; Stumpf, Anne M. "#140350 HAWKINSINURIA". OMIM. Retrieved 14 February 2020.

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Classification	D ICD-10: E72.1 OMIM: 140350 MeSH: D020176 DiseasesDB: 29836

Inborn error of amino acid metabolism

K→acetyl-CoA

Lysine/straight chain	Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria
Leucine	3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease
Tryptophan	Hypertryptophanemia

G→pyruvate→citrate

Glycine

G→glutamate→
α-ketoglutarate

Histidine	Carnosinemia Histidinemia Urocanic aciduria
Proline	Hyperprolinemia Prolidase deficiency
Glutamate/glutamine	SSADHD

G→propionyl-CoA→
succinyl-CoA

Valine	Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease
Isoleucine	2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease
Methionine	Cystathioninuria Homocystinuria Hypermethioninemia
General BC/OA	Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia

G→fumarate

Phenylalanine/tyrosine

Phenylketonuria	6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency
Tyrosinemia	Alkaptonuria/Ochronosis Tyrosinemia type I Tyrosinemia type II Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin	Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome
Tyrosine→Norepinephrine	Dopamine beta hydroxylase deficiency reverse: Brunner syndrome

G→oxaloacetate

Urea cycle/Hyperammonemia (arginine aspartate)	Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency

Transport/
IE of RTT

Other

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