Clinical Guidance

Most children with carbonic anhydrase VA (CA-VA) deficiency reported to date have presented during the newborn period (day 2 of life) or in early childhood (up to age 20 months) with hyperammonemic encephalopathy (i.e., lethargy, feeding intolerance, weight loss, tachypnea, seizures, and coma) [, , , ]. However, the range of severity on presentation is probably not yet completely understood given the small number of reported individuals to date. Data on long-term follow up are limited as the oldest known affected individual is only an adolescent (as of 2021). Almost all of the other affected individuals reported (total number still 20) show normal psychomotor development and no further episodes of metabolic crisis.

Diagnostic Criteria

No consensus clinical diagnostic criteria for carbonic anhydrase VA (CA-VA) deficiency have been published.

Suggestive Findings

Carbonic anhydrase VA (CA-VA) deficiency should be suspected in children with the following clinical and laboratory findings and family history. Clinical findings include neonatal, infantile, or early childhood-onset of metabolic hyperammonemic encephalopathy (like that observed in the urea cycle disorders) with lethargy, feeding intolerance, weight loss, tachypnea, seizures, and coma.

Laboratory findings

Management Guidelines

No clinical practice guidelines for carbonic anhydrase VA (CA-VA) deficiency have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with carbonic anhydrase VA (CA-VA) deficiency, the following evaluations are recommended:

Surveillance Guidelines

Follow up during infancy and early childhood with a metabolic disease specialist every three to six months for physical and neurologic examinations.

• Consider neurodevelopmental testing and measurement of the following: plasma ammonia and amino acids (to check for chronic hyperammonemia and citrulline deficiency as well as general nutritional state); serum lactate and glucose; blood gases; liver parameters; and urine organic acids.