Pterin-4 alpha-carbinolamine dehydratase deficiency (PCDD) is one of the known forms of

tetrahydrobiopterin deficiency Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing int ...

. This condition is associated with mutations of the

PCBD1 Pterin-4-alpha-carbinolamine dehydratase is an enzyme that in humans is encoded by the ''PCBD1'' gene. Function This gene encodes pterin-4 alpha-carbinolamine dehydratase, an enzyme involved in phenylalanine hydroxylation. The enzyme regulates ...

gene. As of 2020, PCDD was the rarest form of BH4 deficiency in terms of cases described in medical literature.

Symptoms

Patients with PCDD are mostly asymptomatic, although they may have transient neurologic deficits in infancy, and sometimes

hypomagnesemia Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, an ...

and nonautoimmune

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

in puberty.

Diagnosis

Pterin-4 alpha-carbinolamine dehydratase deficiency causes

hyperphenylalaninemia Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ( ...

and therefore can be suspected upon finding elevated levels of phenylalanine. To distinguish it from other forms of BH4 deficiency, further analyses are made. PCDD is associated with elevatel levels of primapterin, especially in urine, while

biopterin Biopterins are pterin derivatives which function as endogenous enzyme cofactors in many species of animals and in some bacteria and fungi. The prototypical compound of the class is biopterin (6-(1,2-dihydroxypropyl)-pterin), as shown in the infobo ...

levels range from low to normal, and

neopterin Neopterin is a catabolic product of guanosine triphosphate (GTP), a purine nucleotide. Neopterin belongs to the chemical group known as pteridines. It is synthesised by human macrophages upon stimulation with the cytokine interferon-gamma and is i ...

levels from normal to high.

Treatment

Treatment involves a diet with a low

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

content, and sapropterin to help normalize phenylalanine levels. Since phenylalanine levels in this disease have been reported to be only mildly elevated in the majority of patients, relaxation and discontinuation of phenylalanine-reduced diet and/or sapropterin supplementation can be attempted after the first year of life under careful monitoring of phenylalanine levels, according to a consensus guideline published in 2020.

External links

Hyperphenylalaninemia, BH4-deficient, D
- description in the OMIM compendium.

References

{{medicine-stub Autosomal recessive disorders Congenital disorders